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Adulteration of Mustard Cooking Oil with Argemone Oil: Do Indian Food Regulatory Policies and Antioxidant Therapy Both Need Revisitation?
Abstract
Consumption of adulterated mustard oil (Brassica nigra) with argemone oil (Argemone mexicana) even for a short duration leads to a clinical condition referred as epidemic dropsy. In humans, argemone oil contained in adulterated mustard oil causes oxidative stress and death of red blood cells via met-hemoglobin formation by altering pyridine nucleotide(s) and glutathione redox potential. Argemone oil contamination poses a serious threat to human health and should be checked by appropriate regulatory measures. Antioxidant therapy provides symptomatic relief and should be seriously considered for therapeutic interventions against argemone oil toxicity.
... Argemone oil is extracted from the Argemone Mexicana plant's seeds and added to mustard oil. Its spherical, netted, blackish-brown seeds are remarkably similar to mustard seeds [8]. ...
... For this reason, it sometimes happens that mustard seeds are accidentally or purposely tempered with Argemone Mexicana seeds [8,9]. Cow and buffalo ghee is often mixed with other oils and animal body fat. ...
... Retinal hemorrhages, hypoproteinemia, mild to severe renal azotemia, and anemia are some of its symptoms. Due to the presence of polycyclic aromatic hydrocarbons (PAH), a potent carcinogen, it is very harmful to health [8]. ...
... In this regards the adulteration of mustard oil with argemone oil is a serious issue and critical analytical problem (Gomber et al. 1994;Thatte and Dahanukar 1999;Singh et al. 2000;Ghosh et al. 2005;Xia et al. 2021). Argemone oil contamination in mustard oil is one of the important issues, which are faced by oil processing industries (Das and Khanna 1997;Babu et al. 2007). The source of this contamination and adulteration is the seeds from the matured Argemone mexicana plant (Bui 1974;Babu et al. 2007). ...
... Argemone oil contamination in mustard oil is one of the important issues, which are faced by oil processing industries (Das and Khanna 1997;Babu et al. 2007). The source of this contamination and adulteration is the seeds from the matured Argemone mexicana plant (Bui 1974;Babu et al. 2007). ...
In this present study, a simple, rapid, cheap, sensitive and reproducible HPTLC-MS Method has been developed for the identification of two important bioactive compounds, Sanguinarine and Dihydrosanguinarine in Argemone Mexicana Linn seeds. The work further discussed and developed a sensitive HPTLC – MS method to analyse the adulteration and/or contamination of argemone oil in the edible mustard oil by spiking Sanguinarine and Dihydrosanguinarine as biomarkers. The n-hexane: diethyl ether (1:1 v/v) solvent system has been used as an extraction medium to extract the Sanguinarine and Dihydrosanguinarine from the seeds followed by HPLC-MS detection.
The CAMAG HPTLC system modules consisted with ATS-4, ADC-2, visualizer-2, TLC scanner-4; Derivatizer and TLC-MS interface-2 have been used for sample application, HPTLC plate development, plate photo documentation, scanning of plate, spraying of derivatization reagent and elution of biomarkers directly from HPTLC plate respectively. The n-hexane: acetone (23:7, v/v) and dragendorff’s reagent has been used as mobile phase and derivatization reagent respectively. The UV- spectra and MS data confirmed the detection of selected biomarkers in the samples/spiked samples. Thus, the work highlights the use of HPTLC-MS to develop simple and routine method for the sensitive detection of Sanguinarine and Dihydrosanguinarine in Argemone Mexicana seeds and able to become bases to these biomarkers’ evaluations in other samples such as various edible oils, agro-products, drugs and biomedical products.
... Argemone oil resembles mustard oil with respect to its characteristic odor and color [27]. If it is ingested by human beings it can cause epidemic dropsy and its major symptoms include breathlessness, nausea, lung's crepitating, edema of lower limbs and palpitations, glaucoma and failure of respiratory as well as cardiac system therefore creating serious human health threats and even lethal conditions [28]. Researchers investigated presence of argemone oil in little concentration within mustard oil [27]. ...
... Researchers investigated presence of argemone oil in little concentration within mustard oil [27]. Babu et al [28] reviewed about the epidemic dropsy condition in patients of Patna and Lucknow which occurred due to the intake of mustard oil contamination with Argemone oil. Lakshmi et al [29] reported dropsy outbreak in a single family in Punjab, India because the mustard oil was contaminated with argemone oil. ...
The family of Brassicaceae accounts for one of the earliest cataloged annual oilseed referred to as Mustard. Brassica nigra and Brassica rapa var. toria are two of the commercially important varieties of mustard seed which are endowed with biomedical properties. The present study was designed for the comparative scrutiny of quality and physicochemical parameters of both oilseed mustard varieties. Oil content, near infrared reflectance analysis, moisture content, color, pungency, free fatty acid value, acid value, presence of argemone test and gas chromatography were studied. B. nigra and B. rapa toria showed oil content corresponding to 37.68% and 43.06% respectively. Less moisture content was observed in B. rapa toria (5.33 %) in comparison to B. nigra. Higher color units were investigated in B. nigra in comparison to B. rapa toria. B. rapa toria showed lesser pungency with 0.034 % allyl isothiocynate content. B. nigra illustrated free fatty acid (FFA) content of 0.79% and high acid value (1.58%). While B.rapa toria showed less FFA and acid value. Argemone oil contamination was not seen in oil of both varieties. B. nigra showed 6.45%, 69.25%, 24.29% of saturated, monounsaturated and polyunsaturated fatty acids respectively. B. rapa toria demonstrated valuable gas chromatographic analysis with lesser saturated fatty acid and higher monounsaturated fatty acid. In comparison to B. nigra, higher oil content, lesser moisture, low FFA value, less acid value and favorable fatty acid composition analysis has been shown by B. rapa toria there upon, indicating superior quality of B. rapa toria oilseed.
... Although epidemic dropsy is very well known in India, first reported in 1877 from Calcutta, outbreaks elsewhere are relatively infrequent. Other countries where its occurrence has been reported include Myanmar, the Fiji Islands, Mauritius, Madagascar and South Africa (5,9,10). ...
... Enhanced surveillance of food safety establishments and improved awareness of clinicians and the public to emerging disease conditions for timely detection and handling of adulteration of food oil is critical (9,13). ...
A 17 year old female patient who presented to a tertiary Hospital in Addis Ababa with bilateral painful leg swelling of two months and shortness of breath, associated with cough and haemoptysis of one week duration was reported to the Ministry of Health and the Addis Ababa Health Bureau. The condition was later detected in 18 individuals from 4 households indicating occurrence of an outbreak of unknown cause in Addis Ababa which lasted during May-July 2008.
An outbreak investigation was initiated to identify the cause and prevent further spread, morbidity and mortality.
Using semi-structured questionnaire, quantitative assessment involving individual cases and affected households was conducted to detect aetiology and risk factors. Unaffected households as well as unaffected members of affected households were also included for comparison purpose. Record review of patients visiting hospitals was also done. Data were collected through house to house visits, and using interview of cases admitted to hospital. Samples of cooking oil were collected for laboratory testing. Data analysis was done using SPSS.
A total of 182 patients, 50 (27.5%) males and 132 (72.5%) females, were identified till the outbreak was controlled fully. Age varied from 6-90 years. Death was confirmed in 12 cases, 8 of whom were female. The majority of the patients came from the adjoining Lideta (39.0%) and Kolfe Keranyo (31.9%) subcities. History of illness ranged from less than a week to 12 weeks before presentation. Out of the 106 household members of the 24 affected households identified during the first phase of the investigation, 83 were affected. Most family members who infrequently take meals at home, and children aged 3 years and below were spared. The 21 visited affected households from Kolfe keranyo, Lideta and Bole subcities bought cooking oil produced by a firm in Lideta subcity and all had bought their last supplies in March and April 2008. Samples of cooking food oil taken from this firm and from the affected households were found to have alkaloids of Argemone Mexicana. The number of new cases dropped to zero within 6 weeks after the source was closed.
The occurrence of bilateral leg swelling in more than one family member of affected households, that bought cooking oil from the same source, sparing the toddlers, and those who infrequently take meals at home, further strengthened by laboratory confirmation of presence of argemone alkaloids in the cooking oil samples taken from the affected households and the common sources led to the diagnosis of the outbreak to be epidemic dropsy.
... In dropsy patients SAN exerts its toxic effects on major visceral organs such as the liver, lungs, heart, and kidneys (Upreti et al. 1989;Babu et al. 2006). Substantial data is available regarding the role of AO/SAN in cellular toxicity, oxidative stress, genotoxicity, and carcinogenicity (Das et al. 1991(Das et al. , 2005a2005b;Upreti et al. 1991b;Sen and Maiti 1994;Ansari et al. 2004;2005;Babu et al. 2007). SAN's nucleophilic propensity to bind with cellular thiols, especially sulfur containing proteins, is the key mechanism by which it causes toxicity, which leads to malfunctioning of many regulatory enzymes, most of them thiol proteins, and depletion of cellular antioxidants (Walterova et al. 1981; Bartak et al. 2003;Das et al. 2005a). ...
... The ability of SAN to bind with hepatic P450 may not be a limiting factor in its removal from the body since our results clearly indicate that SAN can easily compete with CO for binding with P450 in dithionate-reduced 3MC-and PB-induced microsomes, but metabolism by these P450s is an important determinant for elimination of SAN from the body and its toxicity. The slow elimination of SAN in rodents and humans (Tandon et al. 1993: Babu et al. 2007) may be due to (i) impairment of the microsomal electron transport chain where electron carriers to P450 such as cytochrome P450 reductase or cytochrome b5 are impaired by SAN, diverting the electron flow onto microsomal membranes causing their damage (Karuzina and Archakov 1994;Vrba et al. 2004), or (ii) oxidative stress which SAN might cause when it forms a MI complex with P450 leading to loss of functional P450 activity (Ortiz de Montellano and Corriea 1983). ...
ABSTRACT Prior studies have shown that argemone oil (AO), responsible for 'Epidemic dropsy', causes inhibition of catalytic activities of Cytochrome P450 (P450). In this study interaction of sanguinarine (SAN) alkaloid, isolated from AO, with rat hepatic P450 was investigated. Hepatic microsomes prepared from 3-methylcholantherene (3MC) treated rats when incubated with SAN (1-3 muM) resulted in a spectral peak at 385 nm and a trough at 415 nm, indicative of Type I binding. Incubation of SAN (50-200 muM) with hepatic microsomes prepared from phenobarbitone (PB) treated rats also showed a Type I spectra with a peak at 395 nm and a trough at 420 nm. Relative binding efficiency (DeltaA(max)/K(s)(app) factor) of SAN with P450 was found to be 1540 and 1030 absorbance units/nmol CYP/M for 3MC and PB induced microsomes, respectively. In a P450 spectral inhibition study SAN showed higher affinity towards 3MC eliciting inhibition at much lesser concentrations (0.25-5 muM) as compared to PB (100-300 muM). The IC50s of SAN with different catalytic markers of P450 isoforms, i.e. ethoxyresorufin-O-deethylase (EROD) for CYP1A1, was 2.8 muM and for methoxyresorufin-O-deethylase (MROD) for CYP1A2 was 2.2 muM in 3MC induced microsomes, while benzoyloxyresorufin-O-deethylase (BROD) for CYP 2B1/1A1 showed an IC50 of 50 muM but pentoxyresorufin-O-deethylase (PROD) for CYP2B1 showed no inhibition even at higher concentrations of SAN (> 60 muM) in PB-induced microsomes. These results indicate that higher affinity of SAN binding towards the CYP1A family may have a role in SAN toxicity.
... Our recent clinical studies suggest that oxidative stress is produced in ED patients, leading to the decrease in levels of antioxidants including ␣-tocopherol and total antioxidant capacity (TAC), which in turn may cause oxidative damage of macromolecules including lipids and proteins in plasma of dropsy patients [5,12]. This may be due to the alterations in pyridine nucleotide (s) and glutathione redox potential causing pro-oxidant environment in erythrocytes leading to destruction of RBCs and enhanced oxidation of hemoglobin which produces normocytic anemia in dropsy patients [4]. ...
... GR is known to play a crucial role in the maintenance of cellular thiol/disulfide redox state [31]. Decrease in activity of GR causes alterations in reducing equivalents such as GSH and pyridine nucleotide(s) leading to the formation of pro-oxidant environment as observed earlier in erythrocytes of dropsy patients [4,6]. Redox state of thiols in particular GSH is important in controlling redox regulated signal transduction pathways [31]. ...
In the present study, the role of ROS and RNS in activation of inflammatory response and associated molecular events during apoptosis of polymorphonuclear leucocytes (PMNs) in patients from an outbreak of argemone oil (AO) poisoning leading to epidemic dropsy in Lucknow, India was undertaken. It was observed that generation of superoxide radical, nitrite formation and phagocytosis (103-429%) were significantly increased in PMNs of dropsy patients. Furthermore, activities of superoxide dismutase and glutathione peroxidase (GPx) (47-79%) were found to be increased while that of catalase and glutathione reductase (GR) (56-57%) were decreased. Lipid and protein oxidation, nitrotyrosine formation and 8-hydroxydeoxyguanosine (8-OHdG) excretion were significantly enhanced with concomitant depletion of GSH levels (67%) in dropsy patients. In addition, significant elevation of IL-6, IL-8 and TNF-alpha (68-406%) in plasma was observed. Apoptosis was enhanced (1.5 folds) with increased (2.0-3.6 folds) caspases 3, 8 and 9 activities along with DNA fragmentation (119%). The results suggest that generation of ROS and RNS along with enhancement of secretion of inflammatory mediators leading to DNA damage followed by apoptosis may have an effect on immune system, which in turn may be responsible for histopathological changes in target organs of dropsy patients.
... To increase profits, edible oils can be adulterated with many similar appearance and low-cost oils which may even harm human health to a different extent depending upon the duration, amount and their uses. Most common adulterants found in mustard oil (MO) are argemone oil (AO) and mineral oils (Babu et al. 2007). ...
Mustard and canola oils are commonly used cooking oils in Asian countries such as India, Nepal, and Bangladesh, making them prone to adulteration. Argemone is a well-known adulterant of mustard oil, and its alkaloid sanguinarine has been linked with health conditions such as glaucoma and dropsy. Utilising a non-destructive spectroscopic method coupled with a chemometric approach can serve better for the detection of adulterants. This work aimed to evaluate the performance of various regression algorithms for the detection of argemone in mustard and canola oils. The spectral dataset was acquired from fluorescence spectrometer analysis of pure as well as adulterated mustard and canola oils with some local and commercial samples also. The prediction performance of the eight regression algorithms for the detection of adulterants was evaluated. Extreme gradient boosting regressor (XGBR), Category gradient boosting regressor (CBR), and Random Forest (RF) demonstrate potential for predicting adulteration levels in both oils with high R2 values.
... Mustard and sesame oils have commonly been adulterated with argemone oil containing toxic benzophenanthridine alkaloids, sanguinarine, and dihydrosanguinarine, and butter yellow, causing several cases of gallbladder cancer and epidemic dropsy; rapeseed adulteration has caused toxic oil syndrome, which is a severe multisystemic disease. Adulteration of mustard cooking oil with argemone oil: do Indian food regulatory policies and antioxidant therapy both need revisitation [20]. Therefore, quantification and identification of the components present in the edible oils become inevitable. ...
Edible oils play a tremendous role in the human diet. The production and consumption of edible oils have extensively increased due to their nutritional and economic significance. As a result of exponential population growth, the demand for edible oil has prompted adulteration, which has become a global crisis. Adulteration causes a variation in the fatty acid profiles, unique to each oil. The addition of adulterants is associated with gallbladder cancer, epidemic dropsy, cardiovascular diseases, hypercholesterolemia, and several other life-threatening diseases. Hence, monitoring the purity of edible oils at regular intervals has become inevitable. This study is to evaluate the quality of edible oils such as sesame, groundnut, coconut, mustard, sunflower, soybean, and olive oils by screening their fatty acids and secondary metabolites composition using gas chromatography-mass spectrometry (GC–MS) and thereby identifying the adulterants in comparison between the unrefined and refined oils. The fatty acid profiles of the unrefined oils were found to be in accordance with the literature survey, whereas the commercially available refined oils were mainly adulterated with palmitic, palmitoleic, stearic, and myristic acids. Contrastingly, numerous health-promoting secondary metabolites have been detected in unrefined oil samples. In conclusion, unrefined oils have nutritional values, and authenticity used for human consumption rather than refined edible oils.
... Often starting as gastroenteritis, the condition progresses to edema, hyperpigmentation, glaucoma, and right heart failure with a 5% mortality (Sharma et al., 1999;Tomar et al., 2015). In lab studies, dropsy patients' blood can be stressed to produce methemoglobin fractions of up to 3.25% compared with normal levels in control blood (Babu et al., 2007). However, we found no specific reports of methemoglobinemia due to contaminated mustard oil. ...
Methemoglobinemia is a sporadic, potentially fatal disease of poor tissue oxygenation in which ferrous hemoglobin (Fe2+) is oxidized to the ferric (Fe3+) state, rendering it incapable of binding oxygen (O2). Fortunately, it is diagnosable and treatable. Here, we present a systematic review of food‐induced methemoglobinemia. PubMed and Embase databases were searched using the term “methemoglobin*,” for articles up to December 31, 2020. Inclusion criteria were confirmed or probable cases of methemoglobinemia with an oxidant confirmed in food or body tissue samples, or the oxidant likely to have come from food. We found 97 articles describing 568 cases. Median age was 6 years (range: 2 weeks to 80 years). Median methemoglobin fraction was 30% (n = 142). Oxidizing agents were predominantly nitrites and nitrates. The commonest type of presentation was children eating vegetables (30%), followed by accidental ingestions (27%), and meat curing misadventures (22%). Favism was found to result in mild methemoglobinemia, highest fraction reported was 15.8%. Of the 35 deaths, 32 were from accidental ingestions (91%). In some fatal cases, diagnosis was likely delayed or missed, and antidote was not administered. The majority of cases survived, even with severe methemoglobin levels of up to 89%, provided that methylene blue was administered. Treatment with methylene blue alone resulted in an average methemoglobin drop of 39.1% (n = 22). Methemoglobinemia cases continue to occur due to accidental exposure, meat curing misadventures, and babies ingesting nitrate‐rich vegetables which have been inappropriately stored. Early recognition of the toxidrome, instituting antidote treatment, and notifying public health authorities are key to improved outcomes.
... In a case highlighted, people used to mix mustard oil (Brassica nigra) with argemone oil but this could lead to epidemic dropsy even if consumed for short time period. This could cause serious threat to human health (Challagundla et al., 2007). ...
Argemone mexicana, a prickly plant commonly called as prickly poppy is found in sub tropical regions and is well known for its medicinal properties. Its potential as a medicinal plant has been practiced traditionally and been prescribed as medicines by Ayurvedic, Unani, Siddha and Homeopathic practices since several years. Each part of plant posses bio active compounds that help in curing ailments like HIV, malaria, ring worm infections, fungal infections, cancer etc. These activities have been studied in vivo and in vitro set up and results have been obtained in favor. Further, phytochemical evaluation has unveiled the presence of compounds like berberine, argemonine, protopine etc, which show curative actions and could be used for treatment of diseases with future preception. This review is a sum up of all literature available through the internet and was searched using keywords ‘Argemone mexicana’, ‘phytochemical importance of Argemone’ and many other exclusive words with respect to different activities scanned for reviewing. The references provided in the papers were also given a thorough look and retrieved the respected data from them too. ‘Scopus’, ‘Pubmed’, ‘Google Scholar’, ‘Research Gate’ were used to search for the relevant papers through different journals available. The literature has then been framed in a way with up gradation about Argemone mexicana and its promising affects seen with the potential of the plant which is still undiscovered but could be utilized as curative methods
... In present study the seeds of A. mexicana were identified in seeds of B. nigra. Previously few researchers [7][8][9][10] worked on the issue of presence of argemone oil in mustard oil. Their study nicely detected the contamination or adulterant in oil. ...
... Mustard oil is the predominant means of cooking in much of the high-risk regions. This oil is often found to be contaminated with Argemone Mexicana seed oil 11,12 leading to the clinical condition epidemic dropsy. 12 Experimental and clinical studies have shown a genotoxic effect of contaminated mustard oil, suggesting its carcinogenic potential. ...
The current study aimed to investigate the role of cooking with mustard oil and other dietary factors in relation to gallbladder cancer (GBC) in high‐ and low‐incidence regions of India. A case–control study was conducted including 1,170 histologically confirmed cases and 2,525 group‐matched visitor controls from the largest cancer hospital in India. Dietary data were collected through a food frequency questionnaire. For oil consumption, we enquired about monthly consumption of 11 different types of cooking oil per family and the number of individuals usually sharing the meal to estimate per‐individual consumption of oil. Information about method of cooking was also requested. Odds ratios (ORs) and 95% confidence intervals (CIs) quantifying the association of GBC risk consumption of different types of oil, method of cooking, and dietary food items, were estimated using logistic regression models, after adjusting for potential confounders. High consumption of mustard oil was associated with GBC risk in both high‐ and low‐risk regions (OR = 1.33, 95% CI = 0.99–1.78; OR = 3.01, 95% CI = 1.66–5.45), respectively. An increased risk of GBC was observed with deep frying of fresh fish in mustard oil (OR = 1.57, 95% CI = 0.99–2.47, p‐value = 0.052). A protective association was observed with consumption of leafy vegetables, fruits, onion and garlic. No association was observed between consumption of meat, spicy food, turmeric, pulses or with any other oil as a cooking medium. The effect of high consumption of mustard oil on GBC risk, if confirmed, has implications for the primary prevention of GBC, via a reduced consumption.
... Consumption of adulterated edible oils has been a cause of ill health, as reported in past [1][2][3]. Periodically, Mustard oil, a major cooking medium in the Indo-gangetic plains, has been known to be adulterated with Argemone oil (AO). ...
... Mustard oil (obtained from Brassica species including B. rapa (syn. campestris) and B. nigra) is used as a frying and cooking medium in North India [167], [168]. Unscrupulous traders, for economic gain, often adulterate mustard oil with cheap argemone oil obtained from Argemone mexicana [169,170]. ...
Black salves are escharotic skin cancer therapies in clinical use since the mid 19th century. Sanguinaria canadensis, a major ingredient of black salve formulations, contains a number of bioactive phytochemicals including the alkaloid sanguinarine. Despite its prolonged history of clinical use, conflicting experimental results have prevented the carcinogenic potential of sanguinarine from being definitively determined.
Sanguinarine has a molecular structure similar to known polyaromatic hydrocarbon carcinogens and is a DNA intercalator. Sanguinarine also generates oxidative and endoplasmic reticulum stress resulting in the unfolded protein response and the formation of 8-hydroxyguanine genetic lesions. Sanguinarine has been the subject of contradictory in vitro and in vivo genotoxicity and murine carcinogenesis test results that have delayed its carcinogenic classification. Despite this, epidemiological studies have linked mouthwash that contains sanguinarine with the development of oral leukoplakia. Sanguinarine is also proposed as an aetiological agent in gallbladder carcinoma.
This literature review investigates the carcinogenic potential of sanguinarine. Reasons for contradictory genotoxicity and carcinogenesis results are explored, knowledge gaps identified and a strategy for determining the carcinogenic potential of sanguinarine especialy relating to black salve are discussed. As patients continue to apply black salve, especially to skin regions suffering from field cancerization and skin malignancies, an understanding of the genotoxic and carcinogenic potential of sanguinarine is of urgent clinical relevance.
... Epidemic dropsy is an acute toxic disease caused by ingestion of edible oil adulterated with Argemone mexicana. Both SNG and DHSNG have been ascribed as the etiological agent responsible for epidemic dropsy (Babu et al., 2006;Babu et al., 2007;Das et al., 2005b). Considering its poor gastrointestinal absorption, it is highly unlikely that SNG is solely responsible for the toxic effect of argemone oil, rather, some other oil component may well be the key player involved in this toxicity (Psotova et al., 2006a). ...
Background:
Cancer is an enormous global health burden, and should be effectively addressed with better therapeutic strategies. Currently, over 60% of the clinically approved anticancer agents are either directly isolated from natural sources or are modified from natural lead molecules. Sanguinarine (SNG), a quaternary benzophenanthridine alkaloid has gained increasing attention in recent years as a potential anticancer agent.
Purpose:
There is a large untapped source of phytochemical-based anticancer agents remaining to be explored. This review article aims to recapitulate different anticancer properties of SNG, and describes some of the molecular targets involved in exerting its effect. It also depicts the pharmacokinetic and toxicological properties of SNG, two parameters important in determining the druggability of a molecule.
Methods:
Numerous in vivo and in vitro published studies have signified the anticancer properties of SNG. In order to collate and decipher these properties, an extensive literature search was conducted in PubMed, ScienceDirect, and Scopus using keywords followed by the evaluation of the relevant articles where the relevant reports are integrated and analyzed.
Results:
Apart from inducing cell death, SNG inhibits pro-tumorigenic processes such as invasion, angiogenesis, and metastasis in different cancers. Moreover, SNG has been shown to synergistically enhance the sensitivity of several chemotherapeutic agents and is effective against a variety of multi-drug resistant cancers.
... Owing to (1) confusion of morphological characteristics and absence of distinguishable features for differentiation; (2) confusion of local common names used; (3) use of local substitutes; and (4) intentional substitution of cheaper materials, adulteration is commonly found and this may sometimes cause adverse effects. For examples, substitution of argemone oil as mustard oil causes oxidative stress and death of red blood cells, resulting in epidemic dropsy, glaucoma or even death (Babu, Khanna, & Das, 2007). Risk of infection by various pathogens is increased with contaminating undeclared pork residues in meat products (Masiri et al., 2016). ...
... To increase the production yield of some PFS, the producer could add different botanical species in the expected pure extracts. A clear example is that of mustard (Brassica nigra) seeds or oil that are intentionally mixed with (Argemone mexicana) causing oxidative stress and posing a serious threat to human health [49,50]. Curcuma longa is classically labelled as spice, dye, and cosmetic, but it is also becoming increasingly important as a medicinal herb. ...
Plant exposures are among the most frequently reported cases to poison control centres worldwide. This is a growing condition due to recent societal trends oriented towards the consumption of wild plants as food, cosmetics, or medicine. At least three general causes of plant poisoning can be identified: plant misidentification, introduction of new plant-based supplements and medicines with no controls about their safety, and the lack of regulation for the trading of herbal and phytochemical products. Moreover, an efficient screening for the occurrence of plants poisonous to humans is also desirable at the different stages of the food supply chain: from the raw material to the final transformed product. A rapid diagnosis of intoxication cases is necessary in order to provide the most reliable treatment. However, a precise taxonomic characterization of the ingested species is often challenging. In this review, we provide an overview of the emerging DNA-based tools and technologies to address the issue of poisonous plant identification. Specifically, classic DNA barcoding and its applications using High Resolution Melting (Bar-HRM) ensure high universality and rapid response respectively, whereas High Throughput Sequencing techniques (HTS) provide a complete characterization of plant residues in complex matrices. The pros and cons of each approach have been evaluated with the final aim of proposing a general user’s guide to molecular identification directed to different stakeholder categories interested in the diagnostics of poisonous plants
... Detailed investigation is required to identify the responsible phytochemical and physiological mechanism(s) which lead to this symptom and the prolonged effect of consumption of the plant and possible mechanisms for detoxification. Seeds of an invasive exotic weed, Argemone mexicana L., are known to affect human health even causing death (Babu et al. 2007), have been found to be eaten in some parts of Konso. There is need to raise awareness of possible detrimental effects of ingesting plant parts that are not commonly known and experience about safety is lacking. ...
This paper presents the knowledge on wild/semi-wild edible plant species (WEPS) of Konso ethnic community of southern Ethiopia. Ethnobotanical information was collected through focus group discussions, observations, interviews, and preference ranking. A total of 154 edible parts were recorded from 127 plant species in which fruit (71), leaves (35) and tubers/roots (18) accounted for the major edible parts. Fruit of Opuntia ficus-indica L., and leaves and young shoots of Leptadenia hastata Vatke were most sought after. Excessive harvesting and acquisition of land for crop cultivation is currently threatening Canthium pseudosetiflorum Bridson, Hyphaene thebaica (L.) Mart., Ficus sycomorus L. and O. ficus-indica, among others. Wise use of these plant species would ensure their sustainable availability and local food sovereignty.
... In addition, it was also observed that depleted plasma GSH may be due to direct utilization of GSH peroxidase to scavenge SANG-induced free radicals production in dropsy patients (10). In a preliminary study, we observed that some of the bioantioxidants including riboflavin and TOCO offered protection to Epidemic Dropsy patients in a limited trial (11,12). Thus, it is quite likely that bioantioxidants may have beneficial effects against AO-and SANG-induced tumorigenicity. ...
Since bioantioxidants in plasma of Epidemic Dropsy patients [a condition caused by consumption of adulterated mustard oil with argemone oil (AO)] were found to be significantly decreased, the beneficial effect of N-acetyl cysteine (NAC) and α-tocopherol (TOCO) against AO- or sanguinarine (SANG)-induced tumorigenicity was undertaken in mice. Topical application of TOCO and NAC either alone or in combination showed significant protection against AO/TPA- and SANG/TPA-induced skin tumorigenicity. Histopathological findings suggest that papillomatous growth in AO/TPA- and SANG/TPA-treated animals were substantially protected following topical application of TOCO or NAC. Further, treatment of TOCO and NAC either alone or in combination to AO/TPA- or SANG/TPA-induced mice significantly decreased lipid peroxidation, along with significant revival in glutathione (GSH) content and activities of tyrosinase, histidase, catalase, SOD, GSH peroxidase, and GSH reductase in skin. In vitro studies showed that TOCO and/or NAC significantly decreased the AO and SANG induced cell proliferation and activation of ERK, p38, JNK MAPKs and NF-κB signaling in HaCaT cells. In summary, TOCO and NAC may be useful in preventing the tumorigenic response of AO and SANG probably by acting as scavenger of free radicals and inhibiting MAPKs and NF-κB signaling.
... The vulnerability of erythrocytes to oxidative stress may also be due to enhanced requirement of molecular oxygen during breathlessness in dropsy patients leading to decomposition of H 2 O 2 by Fenton (Wardman and Candeias, 1996) or Haber-Weiss (Kehrer, 2000) reactions thereby producing hydroxyl radicals. The oxidation of hemoglobin to methemoglobin in erythrocytes of dropsy patients might be one of the reasons for causing breathlessness (Babu et al., 2007). ...
Oxidative damage of biomolecules and antioxidant status in erythrocytes of humans from an outbreak of argemone oil (AO) poisoning in Kannauj (India) and AO intoxicated experimental animals was investigated. Erythrocytes of the dropsy patients and AO treated rats were found to be more susceptible to 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) induced peroxidative stress. Significant decrease in RBC glutathione (GSH) levels (46, 63%) with concomitant enhancement in oxidized glutathione (172, 154%) levels was noticed in patients and AO intoxicated animals. Further, depletion of glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G-6-PDH) and glutathione-S-transferase (GST) (42-52%) was observed in dropsy patients. Oxidation of erythrocyte membrane lipids and proteins was increased (120-144%) in patients and AO treated animals (112-137%) along with 8-OHdG levels in whole blood (180%) of dropsy patients. A significant reduction in alpha-tocopherol content (68%) was noticed in erythrocytes of dropsy patients and hepatic, plasma and RBCs of AO treated rats (59-70%) thereby indicating the diminished antioxidant potential to scavenge free radicals or the limited transport of alpha-tocopherol from liver to RBCs leading to enhanced oxidation of lipids and proteins in erythrocytes. These studies implicate an important role of erythrocyte degradation in production of anemia and breathlessness in epidemic dropsy.
... Our earlier studies have shown that increased generation of oxidants and decreased antioxidant capacity, associated with enhanced lipid peroxidation levels and carbonyl formation in proteins of plasma, is a contributing factor in ED syndrome (Das et al., 2005a;Babu et al., 2007). GSH (L-c-glutamyl-L-cysteinyl glycine), a major thiol-disulfide redox buffer in the cell, is involved in the protection against free radical induced damage through the action of GSH peroxidase (Sies, 1999). ...
Several incidences of adverse effects on human health have been reported in many countries, due to consumption of edible oil adulterated with argemone oil (AO). The clinical manifestation of the disease is commonly referred to as epidemic dropsy. In the present study, we determined the relationship between redox potentials (E(h)) of glutathione/glutathione disulfide (GSH/GSSG), cysteine/cysteine disulfide (Cys/CySS) couples and non-enzymatic antioxidants such as alpha-tocopherol and ascorbic acid status in plasma of dropsy patients (n=14) from an outbreak of argemone oil poisoning in Lucknow (March, 2005), India. Depleted GSH (55%) and concomitant enhancement (163%) of plasma GSSG content was observed in patients (P<0.05). Furthermore, lower content of Cys (42%) and CySS (25%) was noticed in patients (P<0.05) when compared to control subjects. Eh GSH and Eh Cys values were shifted by +46 mV and +12 mV towards more oxidizing environment in patients (P<0.05). In addition, alpha-tocopherol and ascorbic acid contents were found to be depleted significantly (P<0.05) in plasma of patients (59-58%). The alterations in redox potentials and antioxidants in plasma, which are synthesized in liver, may be responsible for histopathological changes in hepatic tissue of patients showing swelling of hepatocytes, fluid accumulation in spaces of Desci along with mild kupfur cell hyperplasia. Over all the present study shows that redox state of GSH/GSSG and Cys/CySS pools become oxidized which inturn causes depletion of alpha-tocopherol and ascorbic acid, thus providing a strategy to distinguish pro-oxidant and antioxidant events in patients.
A recognition solution was developed for the detection of 4-(dimethylamino)azobenzene and translated to prepare a chromogenic strip and an electrochemical sensor.
Over the years, extensive research on mustard oil has revealed the presence of isothiocyanates as pungent toxic compounds and erucic acids as possible health risks. Hence, strategies are needed to remove or reduce the isocyanates and erucic contents while processing the mustard oil. Conversely, due to the presence of monounsaturated fatty acids and omega-3 fatty acids, e.g., erucic acid and α-linolenic acid, mustard oil possesses hypolipidemic effect. The oil rich in erucic acid has demonstrated anti-inflammatory and antioxidant effect that may help in the prevention of obesity-induced metabolic disorders, melanoma, and the Parkinson’s disease. The hypolipidemic effects further potentiate the antidiabetic effect. The presence of allyl isothiocyanate has promising anticancer evidenced by the cell cycle arrest at the G2/M phase. Mustard oil chemical compounds showed antimicrobial action against several pathogenic microorganisms and proved to be useful for active antimicrobial packaging. A few of the studies also reported its antioxidant and antiviral activities. Studies confirmed that allyl isothiocyanate from mustard oil has anti-inflammatory potential when applied topically. The economically motivated adulteration of mustard oil with argemone needs further analytical investigation. Further consideration of the mustard oil benefits-risk ratio and mustard oil optimization are required to improve its health-boosting properties.Graphical Abstract
Argemone mexicana Linn belonging to family papaveraceae is widely distributed plant in tropical and sub-tropical regions of the world. The Papaveraceae, also known as the poppy family, is a family of flowering plants with 44 genera and about 760 species that is significant from an ethnopharmacological perspective. In India, It can be found alongside roads, in fields, and near bodies of water. It has roots, flowers, and leaves. It also goes by the name "Mexican Poppy." The current paper provides a review of Argemone mexicana Linn. thorough chemistry and pharmacology. This plant is one of the most important species in traditional systems of medicine. Despite the fact that alkaloids are mostly prevalent, the plant is a source of a wide variety of chemical elements. Some plant parts have hazardous consequences in addition to pharmacological efficacies. In this article, phytochemical, morphological, microscopical, and pharmacological investigations are reviewed. Current knowledge about this plant's chemistry and pharmacology may be useful for directing researchers who want to conduct additional research in these areas.
Background
Maintaining healthy eating habits among children is challenging due to industrial tactics. There is little research on the effect of nutritional labels and tv ads on the eating habits of children. So the primary aim of the study was to explore the noticeability of the food packaging labels by the children, the information retrieved from the food nutrition labels, and their role in increased frequency of eating out in addition to the perceptions of their parents about the television ads.
Methods
A cross-sectional study was conducted at schools in Punjab, India. Using multi-stage stratified random sampling, we included 722 school-going children aged 14–18 and their parents. A structured predefined questionnaire collected data using a four-point Likert scale. Descriptive statistics and binary logistic regression were used to draw our inferences.
Results
About 46% of children were eating out > 3 times a week. Nearly 49% said they never looked at the expiry dates on the food packet, and 40% have yet to notice the quality certification. Nearly half do not understand the components of the food label, and 59% said they never changed their buying behavior because of the label. Only 37% of parents expressed their concerns about the timing of the ads when children watch television, while only 25.5% were concerned about the accuracy of the information. Concerns of the parents regarding the timing of the ads, and celebrity endorsements, were potential predictors for the increased frequency of eating out by the children.
Conclusions
Low awareness regarding the utility of nutrition labels and minimal concerns of the parents increase the frequency of eating out. Unification of our existing policies regarding food labels and tv advertisements to develop family-centric interventions will bring us one step closer to improving the enabling environment to curb the growing menace of childhood obesity.
A transcriptomic approach was employed to describe a set of putatively protein-coding sequences involved in biosynthesis of berberine and sanguinarine; the two major benzylisoquinoline alkaloids (BIA) from Argemone mexicana (L.; Papaveraceae). A robust de novo assembled transcriptome was obtained from developing seedlings. Initial screening identified 514 unigenes, from eight different Pfam domains, such as Cyt-P450 dependent proteins, which are recurrently involved in BIA biosynthesis. Additional annotation by KEGG Orthology and Gene Ontology supported putative participation of the selected proteins in alkaloid biosynthesis. Moreover, in silico structure prediction of sanguinarine reductase (SanR), dihydrobenzophenantridine oxidase (DHBO) and tetrahydroprotoberberine oxidase (STOX), involved in the last reactions of sanguinarine and berberine biosynthesis, fitted with that of previously characterized proteins from related species further supporting proper annotation. Hence, the pipeline analysis presented could provide a comprehensive description of the biosynthetic potential of this plant through the functionality associated with its transcripts.
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the United States (US) and worldwide. Among South Asians living in the US, ASCVD risk is four-fold higher than the local population. Cardioprotective dietary patterns necessitate replacement of dietary saturated fats with healthier oils such as canola, corn, olive, soybean, safflower, and sunflower oil. Mustard oil is a liquid oil that is low in saturated fatand is popular in South Asia.It contains a large proportion of erucic acid, a fatty acid associated with myocardial lipidosis in rodents. This evidence prompted the US Food and Drug Administration (FDA) to ban the use of mustard oil for cooking. However, Australia, New Zealand and the European Union (27 countries) have established upper limits for tolerable intake of mustard oil. In contrast mustard oil is one of the most popular cooking oils in Asia, particularly in India where it is recommended as a heart-healthy oil by the Lipid Association of India (LAI). The conflict between various guidelines warrants clarification, particularly because use of mustard oil in cooking is increasing among both Americans and Indian immigrants in the US, despite the FDA ban on human consumption of mustard oil. Hence, we endeavored to: 1) Review current evidence regarding potentially harmful versus beneficial effects of cooking with mustard oil, 2) Clarify the basis for disparities between the FDA ban on human consumption of mustard oil and dietary recommendations from the LAI and other groups, and³ Provide practical suggestions for Indians and other South Asians who are accustomed to consuming mustard oil on ways to incorporate alternate heart-healthy oils (E.g. Canola, Olive, Sunflower, Soybean oil) in the diet while enhancing flavor and texture of food. A new FDA review is recommended on the safety limits of erucic acid because 29 countries have allow limited amounts of mustard oil (erucic acid) for human consumption and also because there are some health benefits that have been reported for mustard oil in humans.
Plant secondary metabolites are emerging as attractive alternatives in the development of therapeutics against infectious and chronic diseases. Due to the present pandemic, therapeutics showing toxicity against bacterial pathogens and viruses are gaining interest. Plant metabolites of terpenoid and phenylpropanoid categories have known antibacterial and antiviral properties. These metabolites have also been associated with toxicity to eukaryotic cells in terms of carcinogenicity, hepatotoxicity, and neurotoxicity. Sensing methods that can report the exact antibacterial dosage, formation, and accumulation of these antibacterial compounds are needed. The whole-cell reporters for such antibacterial metabolites are cost-effective and easy to maintain. In the present study, battery of toxicity sensors containing fluorescent transcriptional bioreporters was constructed, followed by fine-tuning the response using gene-debilitated E. coli mutants. This study shows that by combining regulatory switches with chemical genetics strategy, it may be possible to detect and elucidate the mode of action of effective antibacterial plant secondary metabolites - thymol, cinnamaldehyde, eugenol, and carvacrol in both pure and complex formats. Apart from the detection of adulteration of pure compounds present in complex mixture of essential oils, this approach will be useful to detect authenticity of essential oils and thus reduce unintended harmful effects on human and animal health.
Adulteration of food refers to adding to or subtracting any material from food and making it detrimental to one’s health and unsafe for consumption. Population explosion and increased urbanization have turned food traders more profit-oriented through increasing food production and sales. As a result, food adulteration is becoming a growing menace in the world, seriously affecting the synthesis and distribution of food, starting from the field to the fork, and making the food unsafe at major levels. According to the World Health Organization, an estimated two million people, including children, are directly or indirectly face fatality due to the consumption of unsafe food and impure water annually. There are different forms of food adulteration which affect the food integrity and authenticity. Proper identification of food adulterants and quantification are becoming a global challenge nowadays as it is a long procedure involving sample preparation and analysis. However, specific and accurate analysis is also not that easy as it often leads to false positives. This affects the food marketing sector as well. Scarcity of high throughput technologies for easy and prompt identification of food adulterants paves the way for exploiting the consumers for trader’s profit. This chapter gives a detailed account of the currently available innovative technologies that could be used for easy identification and quantification of food adulterants. These include chromatographic methods, chromatography coupled with mass spectrometry, spectroscopic methods including vibrational spectroscopies: near-infrared, mid-infrared, Raman; NMR spectroscopy, Fourier transform, etc.
Vegetable oils are edible oils which are extracted from the plants usually from their seeds like sunflower, mustard, palm, coconut etc. which majorly contribute to the daily diet, vegetable oils can be easily adulterated and purity of the edible oil is a big concern. In this research article different optical spectroscopy methods includes Raman and Fourier transfer infrared (FTIR) spectroscopy have been used to compute the purity and investigate the adulteration in edible oils which are commonly used and it also aims to achieve an easy and conventional way to analyse the purity of the vegetable oils.
The use of natural products derived from plants as medicines precedes even the recorded human history. In the past few years there were renewed interests in developing natural compounds and understanding their target specificity for drug development for many devastating human diseases. This has been possible due to remarkable advancements in the development of sensitive chemistry and biology tools. Sanguinarine is a benzophenanthridine alkaloid derived from rhizomes of the plant species Sanguinaria canadensis. The alkaloid can exist in the cationic iminium and neutral alkanolamine forms. Sanguinarine is an excellent DNA and RNA intercalator where only the iminium ion binds. Both forms of the alkaloid, however, shows binding to functional proteins like serum albumins, lysozyme and hemoglobin. The molecule is endowed with remarkable biological activities and large number of studies on its various activities has been published potentiating its development as a therapeutic agent particularly for chronic human diseases like cancer, asthma, etc. In this article, we review the properties of this natural alkaloid, and its diverse medicinal applications in relation to how it modulates cell death signaling pathways and induce apoptosis through different ways, its utility as a therapeutic agent for chronic diseases and its biological effects in animal and human models. These data may be useful to understand the therapeutic potential of this important and highly abundant alkaloid that may aid in the development of sanguinarine-based therapeutic agents with high efficacy and specificity.
Food adulteration including adulteration of edible oils may cause serious health problems. One of the most common edible adulterants is argemone oil. An outbreak of epidemic dropsy occurred in Addis Ababa during May-June, 2008. One hundred and eighty two cases were recorded with twelve confirmed deaths. Dietary history of the cases revealed that vegetable oils were the usual cooking medium.
The aim of the study was hence to investigate the causes of this outbreak.
Contaminant identification was done using standard chemical tests, complemented with TLC. Toxicity study was done using Swiss albino mice feed with contaminated and non contaminated standard diet for 30 days.
Laboratory investigation of the edible oils has indicated that 47 of the 280 edible oils analyzed were adulterated with argemone oil. About 81% of the edible oil samples collected from Lideta sub-city were adulterated with argemone oil. Toxicological investigation of the adulterated oils also indicated typical features of argemone alkaloid poisoning in mice.
Results of both laboratory analysis and toxicological studies confirmed consumption of edible oils adulterated with argemone oil as the cause of epidemic dropsy in Addis Ababa.
We report a fiber optic probe suitable for measuring the wavelength dispersion of liquids. The measuring probe is made from an extrinsic fiber-optic cavity formed by a lensed photonic crystal fiber (PCF) and a micro-mirror. The custom-designed lensed PCF plays a dual role of collimator to help realize a long cavity length of the order of millimeters and as an efficient reflector to form the reference beam. The length of the cavity used in the experiment is about 1620 μm. In this article, we present the analytical method of obtaining dispersion of the liquid sample from the spectral interferogram of a single-arm or common path interferometer. Sodium chloride salt solutions with varied concentrations are used as an example to demonstrate the efficacy of the instrument. The index change with concentration is found to be linear at low concentrations and deviates from linearity as it approaches saturation.Research Highlights► Fiber optic extrinsic cavity sensor based on lensed photonic crystal fiber. ► Long cavity of about 1620 μm suitable for characterizing liquids. ► Analytical method of obtaining dispersion from spectral interferometry. ► Experimentally found that dispersion of salt water is linear at low concentrations.
Plant poisonings are a major problem for livestock producers. The majority of these episodes are due to alkaloid constituents, encompassing numerous plant species. Reviews of the problem have traditionally been organized on the basis of plant families and genera, and less frequently by the animal species and/or organs affected. This review is organized on the basis of the structural classes of alkaloids responsible, emphasizing the actual toxin and mechanism of action, and correlating similar mechanisms of toxicity across disparate plant species, together with structure–activity relationships. Although livestock poisonings by alkaloids are worldwide in nature, this chapter focuses on situations within North America, but covers analogous poisonings in other parts of the world when the same class of alkaloid and plant family is involved. Disease states include acute and chronic poisonings, hepatotoxicity, pulmonary toxicity, teratogenicity, neurotoxicity, cardiotoxicity, reproductive problems, and failure to thrive. The potential biomedical applications of some of the alkaloids are discussed. Specific classes dealt with are pyrrolidine, piperidine, bipiperidine, pyridine, polyhydroxy indolizidine, quinolizidine, tropane, pyrrolizidine, isoquinoline, diterpene, and steroidal alkaloids.
The quaternary benzo[c]phenanthridine alkaloid sanguinarine (SG) is the main component of Sangrovit, a natural livestock feed additive. Dihydrosanguinarine (DHSG) has recently been identified as a SG metabolite in rat. The conversion of SG to DHSG is a likely elimination pathway of SG in mammals. This study was conducted to evaluate the toxicity of DHSG in male Wistar rats at concentrations of 100 and 500 ppm DHSG in feed for 90 days (average doses of 14 and 58 mg DHSG/kg body weight/day). No significant alterations in body or organ weights, macroscopic details of organs, histopathology of liver, ileum, kidneys, tongue, heart or gingiva, clinical chemistry or hematology markers in blood in the DHSG-treated animals were found compared to controls. No lymphocyte DNA damage by Comet assay, formation of DNA adducts in liver by 32P-postlabeling, modulation of cytochrome P450 1A1/2 or changes in oxidative stress parameters were found. Thus, repeated dosing of DHSG for 90 days at up to 500 ppm in the diet (i.e. approximately 58 mg/kg/day) showed no evidence of toxicity in contrast to results published in the literature. In parallel, DHSG pharmacokinetics was studied in rat after oral doses 9.1 or 91 mg/kg body weight. The results showed that DHSG undergoes enterohepatic cycling with maximum concentration in plasma at the first or second hour following application. DHSG is cleared from the body relatively quickly (its plasma levels drop to zero after 12 or 18 h, respectively).
A method for measurement of both oxidized (GSSG) and reduced (GSH) glutathione has been developed, with use of o-phthalaldehyde (OPT) as a fluorescent reagent. The method takes advantage of the reaction of GSH with OPT at pH 8 and of GSSG with OPT at pH 12; GSH can be complexed to N-ethylmaleimide to prevent interference of GSH with measurement of GSSG. The method gave “recoveries” of 91 to 110% for both GSH and GSSG and was quite specific for glutathione; and none of the manipulations appeared to influence the amount of glutathione present in the tissue. Results for GSH levels agreed well with earlier reports but levels of GSSG estimated here were higher than earlier reported values. The reasons for the apparently higher levels of GSSG are discussed.
Glucose 6-phosphate dehydrogenase (G6PD) is a housekeeping enzyme encoded in mammals by an X-linked gene. It has important functions in intermediary metabolism because it catalyzes the first step in the pentose phosphate pathway and provides reductive potential in the form of NADPH. In human populations, many mutant G6PD alleles (some present at polymorphic frequencies) cause a partial loss of G6PD activity and a variety of hemolytic anemias, which vary from mild to severe. All these mutants have some residual enzyme activity, and no large deletions in the G6PD gene have ever been found. To test which, if any, function of G6PD is essential, we have disrupted the G6PD gene in male mouse embryonic stem cells by targeted homologous recombination. We have isolated numerous clones, shown to be recombinant by Southern blot analysis, in which G6PD activity is undetectable. We have extensively characterized individual clones and found that they are extremely sensitive to H2O2 and to the sulfydryl group oxidizing agent, diamide. Their markedly impaired cloning efficiency is restored by reducing the oxygen tension. We conclude that G6PD activity is dispensable for pentose synthesis, but is essential to protect cells against even mild oxidative stress.
Redox state is a term used widely in the research field of free radicals and oxidative stress. Unfortunately, it is used as a general term referring to relative changes that are not well defined or quantitated. In this review we provide a definition for the redox environment of biological fluids, cell organelles, cells, or tissue. We illustrate how the reduction potential of various redox couples can be estimated with the Nernst equation and show how pH and the concentrations of the species comprising different redox couples influence the reduction potential. We discuss how the redox state of the glutathione disulfide-glutathione couple (GSSG/2GSH) can serve as an important indicator of redox environment. There are many redox couples in a cell that work together to maintain the redox environment; the GSSG/2GSH couple is the most abundant redox couple in a cell. Changes of the half-cell reduction potential (E(hc)) of the GSSG/2GSH couple appear to correlate with the biological status of the cell: proliferation E(hc) approximately -240 mV; differentiation E(hc) approximately -200 mV; or apoptosis E(hc) approximately -170 mV. These estimates can be used to more fully understand the redox biochemistry that results from oxidative stress. These are the first steps toward a new quantitative biology, which hopefully will provide a rationale and understanding of the cellular mechanisms associated with cell growth and development, signaling, and reductive or oxidative stress.
We report a fiber optic probe suitable for measuring the wavelength dispersion of liquids. The measuring probe is made from an extrinsic fiber-optic cavity formed by a lensed photonic crystal fiber (PCF) and a micro-mirror. The custom-designed lensed PCF plays a dual role of collimator to help realize a long cavity length of the order of millimeters and as an efficient reflector to form the reference beam. The length of the cavity used in the experiment is about 1620 μm. In this article, we present the analytical method of obtaining dispersion of the liquid sample from the spectral interferogram of a single-arm or common path interferometer. Sodium chloride salt solutions with varied concentrations are used as an example to demonstrate the efficacy of the instrument. The index change with concentration is found to be linear at low concentrations and deviates from linearity as it approaches saturation.Research Highlights► Fiber optic extrinsic cavity sensor based on lensed photonic crystal fiber. ► Long cavity of about 1620 μm suitable for characterizing liquids. ► Analytical method of obtaining dispersion from spectral interferometry. ► Experimentally found that dispersion of salt water is linear at low concentrations.
A water-soluble (at pH 8) aromatic disulfide [5,5'-dithiobis(2-nitrobenzoic acid)] has been synthesized and shown to be useful for determination of sulfhydryl groups. Several applications have been made to show its usefulness for biological materials. A study of the reaction of this disulfide with blood has produced some evidence for the splitting of disulfide bonds by reduced heme.
In the present study, the role of ROS and RNS in activation of inflammatory response and associated molecular events during apoptosis of polymorphonuclear leucocytes (PMNs) in patients from an outbreak of argemone oil (AO) poisoning leading to epidemic dropsy in Lucknow, India was undertaken. It was observed that generation of superoxide radical, nitrite formation and phagocytosis (103-429%) were significantly increased in PMNs of dropsy patients. Furthermore, activities of superoxide dismutase and glutathione peroxidase (GPx) (47-79%) were found to be increased while that of catalase and glutathione reductase (GR) (56-57%) were decreased. Lipid and protein oxidation, nitrotyrosine formation and 8-hydroxydeoxyguanosine (8-OHdG) excretion were significantly enhanced with concomitant depletion of GSH levels (67%) in dropsy patients. In addition, significant elevation of IL-6, IL-8 and TNF-alpha (68-406%) in plasma was observed. Apoptosis was enhanced (1.5 folds) with increased (2.0-3.6 folds) caspases 3, 8 and 9 activities along with DNA fragmentation (119%). The results suggest that generation of ROS and RNS along with enhancement of secretion of inflammatory mediators leading to DNA damage followed by apoptosis may have an effect on immune system, which in turn may be responsible for histopathological changes in target organs of dropsy patients.
The reaction of lipid peroxides in animal tissues with thiobarbituric acid was dependent on pH of the reaction mixture as was the case for linoleic acid hydroperoxide. The optimum pH was found to be 3.5. Taking this fact into consideration, a standard procedure for the assay of lipid peroxide level in animal tissues by their reaction with thiobarbituric acid was developed as follows. Ten percent ( tissue homogenate was mixed with sodium dodecyl sulfate, acetate buffer (pH 3.5), and aqueous solution of thiobarbituric acid. After heating at 95°C for 60 min, the red pigment produced was extracted with n-butanol-pyridine mixture and estimated by the absorbance at 532nm. As an external standard, tetramethoxy-propane was used, and lipid peroxide level was expressed in terms of nmol malondialdehyde. Using this method, the liped peroxide level in the liver of rats suffering from carbon tetrachloride intoxication was investigated. The results were in good agreement with previously reported data obtained by measuring diene content.
An attempt was made to explore the scope of the bio-antioxidants in the management of symptoms of epidemic dropsy caused by argemone alkaloids, sanguinarine and dihydrosanguinarine. The study was performed on 24 randomly selected epidemic dropsy cases who consumed argemone contaminated mustard oil. On examination the cases revealed characteristic pitting edema over limbs (95.8%) accompanied by tenderness (79.2%) and diffuse erythema (95.8%). Tachycardia was present in 1/3 of the examined cases while elevated jugular venous pressure was seen in over 40% of the cases. In two of the cases, reddish-purplish blotches over lower limbs, not raised and which blanched on pressure, was an unusual feature. Chest X-ray revealed pulmonary congestion in 5 cases. ECG performed in 3 cases with severe breathlessness, showed non-specific ST-T changes most marked in L2,L3, avF and V2-V6 which reversed on recovery. Treatment with a combination of antioxidants, riboflavin and tocopherol showed improvement in pain in lower limbs (75%), edema (83.3%) and erythema (66.6%).
This report represents the findings of an Expert Panel on the safety of Sanguinaria extract used in Viadent oral rinse and toothpaste products and represents an independent review of the Sanguinaria extract toxicologic data base. It is based on reviews and discussions of the data base by all members of the Expert Panel on Sanguinaria extract. The Panel concluded that the data base on Sanguinaria extract is substantial and indicates that Sanguinaria extract is safe in its present use in Viadent products based on a large margin of safety between levels of human exposure and levels found to produce minimum effect or to be without adverse effect in animals. The panel further concluded that published literature suggesting an association between human exposure to Sanguinaria extract and potential reproductive, cardiovascular, or ocular toxicity, or carcinogenicity is largely anecdotal, unfounded, and not corroborated by or consistent with the substantial data base that was subjected to peer review.
Short- and long-term testing of sanguinaria toothpaste and oral rinse used individually have yielded both positive and negative results. This review evaluates the results of a number of clinical trials testing the regimen use of sanguinaria products for periods ranging from 14 days to six months. Review of these trials establishes the clinical efficacy of the two products in combination. The regimen approach produces consistently positive reductions in plaque, gingival inflammation and bleeding parameters for up to six months with no adverse hard tissue effects and only one reversible adverse soft tissue effect observed among the 260 subjects tested. In addition, no adverse microbiological shifts in the normal oral flora were observed.
Sanguinarine chloride, a quaternary salt of a benzophenanthrene alkaloid, was phototoxic to catalase-deficient strains of Escherichia coli but not to Trichoplusia ni (cabbage looper moth larvae), an insect with high levels of catalase activity. Chemical analyses confirm that sanguinarine is an efficient producer of H2O2. This differential toxicity suggests that the mode of phototoxic action involves production of H2O2 which could be detoxified in many organisms by catalase.
A simplified and reliable assay for the determination of erythrocyte pyridine nucleotide (NAD and NADP) concentrations, as well as the ratio of the reduced [NADH/NADPH] to oxidized [NAD+/NADP+] nucleotide, is important in understanding both normal and abnormal red blood cells (RBC). However, previously published methods for quantitating pyridine nucleotides are inappropriate for RBC, difficult to use, or inaccurate. The method described within this paper provides for both improved reliability and ease of use. In addition, we have documented that significant pools of NADPH and NADH are tightly bound to proteins (e.g., catalase) and not detectable by many of the assay systems previously used. This results in a significant change in not only total RBC pyridine nucleotide content but also in the ratio of reduced to nonreduced nucleotide.
Energy has been proposed to play a role in the ability of cells and tissues to defend against oxidative stress, even though the ultimate antioxidant capacity of a tissue is determined by the supply of reducing equivalents. The pathways involved in supplying reducing equivalents in response to an oxidative stress remain unclear, particularly if competing reactions such as ATP synthesis are active. Glutathione (GSH), a major component of cellular antioxidant systems, is maintained in the reduced form by glutathione reductase. Although this enzyme is specific for NADPH, the ability of intact cells, isolated mitochondria (which are a major source of free radicals and contain antioxidant systems independent of the rest of the cell), and whole tissues to supply reducing equivalents and maintain normal levels of GSH appears to involve NADH. This article reviews available data regarding the source and pathways by which reducing equivalents are made available to reduce exogenous oxidants, and suggests energy is not a factor. An improved understanding of the mechanism by which reducing equivalents are supplied by tissues to respond to an oxidative stress may direct future research toward designing strategies for augmenting the ability of tissues to defend themselves against oxidative stress induced by reperfusion or xenobiotics.
1. A new method has been developed for measuring the total antioxidant capacity of body fluids and drug solutions, based on the absorbance of the ABTS*+ radical cation.
2. An automated method for use on a centrifugal analyser, as well as a manual method, is described.
3. The procedure has been applied to physiological antioxidant compounds and radical-scavenging drugs, and an antioxidant ranking was established based on their reactivity relative to a 1.0 mmol/l Trolox standard.
4. The Trolox equivalent antioxidant capacity of plasma from an adult reference population has been measured, and the method optimized and validated.
5. The method has been applied to investigate the total plasma antioxidant capacity of neonates and how this may be compromised in prematurity.
An imbalance between oxidants and antioxidants in favour of the oxidants, potentially leading to damage, is termed 'oxidative stress'. Oxidants are formed as a normal product of aerobic metabolism but can be produced at elevated rates under pathophysiological conditions. Antioxidant defense involves several strategies, both enzymatic and non-enzymatic. In the lipid phase, tocopherols and carotenes as well as oxy-carotenoids are of interest, as are vitamin A and ubiquinols. In the aqueous phase, there are ascorbate, glutathione and other compounds. In addition to the cytosol, the nuclear and mitochondrial matrices and extracellular fluids are protected. Overall, these low molecular mass antioxidant molecules add significantly to the defense provided by the enzymes superoxide dismutase, catalase and glutathione peroxidases.
Consumption of oil extracted from accidental or deliberate contamination of argemone seed to mustard seed is known to pose a clinical condition popularly referred to as Epidemic Dropsy. Several outbreaks of Epidemic Dropsy have occurred in the past in India as well as in Mauritius, Fiji Island, and South Africa. Clinico-epidemiological manifestations of argemone oil poisoning include vomiting, diarrhea, nausea, swelling of limbs, erythema, pitting edema, breathlessness, etc. In extreme cases, glaucoma and even death due to cardiac arrest have been encountered. The toxicity of argemone oil has been attributed to two of its physiologically active benzophenanthridine alkaloids, sanguinarine and dihydrosanguinarine. Histopathological studies suggest that liver, lungs, kidney, and heart are the target sites for argemone oil intoxication. Studies have shown to elucidate the cocarcinogenic potential of argemone oil that can be correlated with the binding of sanguinarine with a DNA template. Pharmacological response in intestine revealed immediate stimulation of tone and peristaltic movements of the gut in the sanguinarine-treated animals. Argemone oil/Sanguinarine caused a decrease in hepatic glycogen levels which may be due to the activation of glycogenolysis leading to an accumulation of pyruvate in the blood of Epidemic Dropsy cases. The increase in pyruvate levels causes uncoupling of oxidative phosphorylation leading to breathlessness, as observed in patients. Sanguinarine has been shown to inhibit Na+, K(+)-ATPase activity of different organs such as brain, heart, liver, intestine, and skeletal muscle, which may be due to the interaction with the glycoside receptor site on ATPase enzyme, thereby causing a decrease in the active transport of glucose. Argemone oil/alkaloid showed a Type II binding spectra with hepatic cytochrome P-450 (P-450) protein, thereby causing loss of P-450 content and an impairment of phase I and phase II enzymes. A green fluorescent metabolite of sanguinarine, benzacridine was detected in the milk of grazing animals. The delayed appearance of this metabolite in urine and feces of experimental animals suggests the slow elimination of the alkaloid. Argemone oil enhances hepatic microsomal and mitochondrial lipid peroxidation, indicating that these two organelles are the sites of membrane damage. Furthermore, studies suggest that singlet oxygen and hydroxyl radical are involved in argemone oil toxicity. Several bioantioxidants show protective effect in argemone oil-induced toxicity in experimental animals. The line of treatment in argemone-intoxicated epidemics has so far been only symptomatic, and specific therapeutic measures are still lacking, although it has been suggested that diuretics, bioantioxidants, steroids, vitamins, calcium- and protein-rich diet had some beneficial effects on Epidemic Dropsy cases.
This study was undertaken to compare and contrast biomarkers and ploidy data from maxillary gingiva leukoplakias associated with dentifrices and mouthrinses containing the herbal compound sanguinaria with other forms of oral benign and premalignant mucosal keratosis.
Representative archived specimens of benign keratosis, sanguinaria-associated keratosis, and keratosis with dysplasia were used for computerized image analysis and biomarker immunohistochemical assays to assess ploidy, DNA content, and p53 and proliferating cell nuclear antigen immunoreactivity of nuclei.
DNA content was significantly higher and higher numbers of cell populations with hyperploid nuclei were encountered in the dysplastic group than in the other two groups (P <.001). Sanguinaria-associated keratosis did not harbor significant numbers of p53-expressing nuclei, yet it showed a significant elevation in proliferating cell nuclear antigen-labeled nuclei in total, in the basal layer, and in the spinous layer in comparison with benign keratoses (P <.001). In addition, 1.5% of the sanguinaria-associated leukoplakia epithelial cell population was characterized by nuclei with a greater than 4-fold increase in DNA content.
Sanguinaria-associated keratoses show some marker and image analysis profiles similar to those of non-sanguinaria dysplastic lesions of the lip and mucosa. Preparations containing sanguinaria should be avoided until the risk for malignant transformation is determined.
A major outbreak of epidemic dropsy occurred in Delhi, India, in August-September 1998, due to the consumption of contaminated mustard oil.
The clinical data of 212 adult patients of epidemic dropsy who presented to our hospital is analysed.
Pitting pedal oedema (100%), skin erythema (75%), limb tenderness (63%), diarrhea (51%) and hepatomegaly (34%) were the prominent clinical manifestations observed in the patients. Superficial retinal haemorrhages and retinal venous dilatation was observed on fundus examination and 9% of patients developed an open angle glaucoma over a three month follow up period. Cardiac failure was present in 14% of patients. Most patients had mild disease which responded to cessation of mustard oil consumption, bed rest, diuretics and antioxidants. There were six deaths, all of whom had intractable cardiac failure. A unique feature of this outbreak was the documentation of acute renal failure in three patients, a phenomenon never described previously.
Strict law enforcement to prevent the contamination of edible oils is essential to avoid the occurrence of future similar outbreaks.
About 17 cases with clinical syndrome suggestive of epidemic dropsy attended to the B P Koirala Institute of Health Sciences, Dharan, for treatment. These cases were from three villages of Saptari district in eastern Nepal. Some of the mustard oil samples were tested positive with Nitric acid test. In the wake of this, an extensive field investigation was conducted covering a wider area in these villages.
Gestational hypertension during the third trimester reflects an exaggerated maternal inflammatory response to pregnancy. We hypothesized that oxidative stress present even in normal pregnancy becomes uncompensated in hypertensive patients. A glucose-6-phosphate dehydrogenase (G6PD) activity sufficient to meet the increased reductive equivalent need of the cells is indispensable for defense against oxidative stress. The erythrocyte glutathione redox system was studied, where G6PD is the only NADPH source. The glutathione (GSH) redox status was measured both in vivo and after an in vitro oxidative challenge in pregnant women with gestational hypertension (n = 19) vs. normotensive pregnant subjects (n = 18) and controls (n = 20). An erythrocyte GSH depletion with an increase in the oxidized form (GSSG) resulted in an elevated ratio GSSG/GSH (0.305 +/- 0.057; mean +/- SD) in hypertensive pregnant women vs. normotensive pregnant or control subjects (0.154 +/- 0.025; 0.168 +/- 0.073; p <.001). In hypertensive pregnant patients, a "GSH stability" decrease after an in vitro oxidative challenge suggested a reduced GSH recycling capacity resulting from an insufficient NADPH supply. The erythrocyte GSSG/GSH ratio may serve as an early and sensitive parameter of the oxidative imbalance and a relevant target for future clinical trials to control the effects of antioxidant treatment in women at increased risk of the pre-eclampsia syndrome.
Redox state is a term used widely in the research field of free radicals and oxidative stress. Unfortunately, it is used as a general term referring to relative changes that are not well defined or quantitated. In this review we provide a definition for the redox environment of biological fluids, cell organelles, cells, or tissue. We illustrate how the reduction potential of various redox couples can be estimated with the Nernst equation and show how pH and the concentrations of the species comprising different redox couples influence the reduction potential. We discuss how the redox state of the glutathione disulfide-glutathione couple (GSSG/2GSH) can serve as an important indicator of redox environment. There are many redox couples in a cell that work together to maintain the redox environment; the GSSG/2GSH couple is the most abundant redox couple in a cell. Changes of the half-cell reduction potential (E(hc)) of the GSSG/2GSH couple appear to correlate with the biological status of the cell: proliferation E(hc) approximately -240 mV; differentiation E(hc) approximately -200 mV; or apoptosis E(hc) approximately -170 mV. These estimates can be used to more fully understand the redox biochemistry that results from oxidative stress. These are the first steps toward a new quantitative biology, which hopefully will provide a rationale and understanding of the cellular mechanisms associated with cell growth and development, signaling, and reductive or oxidative stress.
The interaction of sanguinarine with right-handed (B-form), left-handed (Z-form) and left-handed (HL-form) structures of poly(dG-dC).poly(dG-dC) has been investigated by measuring the circular dichroism (CD) and UV-absorption spectral analysis. Sanguinarine binds strongly to the B-form DNA and does not bind to Z-form or HL-form, but it converts the Z-form and the HL-form back to the bound right handed form as evidenced from CD spectroscopy. Sanguinarine inhibits the rate of B to Z transition under ionic conditions that otherwise favour the left-handed conformation of the polynucleotides. UV absorption kinetic studies show that the Z-form reverses back to B-form to B-form on binding to sanguinarine. Binding isotherms obtained from spectrophotometric data show that sanguinarine binds strongly to the B-form polymer in a non-cooperative manner, in sharp contrast to the highly cooperative interaction under Z-form and HL-form polynucleotides. These studies reveal that the alternating GC sequence undergoes defined conformational changes and interacts with sanguinarine which may be an important aspect in understanding its extensive biological activities.
Redox-signaling mechanisms function in cell regulation and growth control. Agents altering glutathione (GSH) concentration affect the transcription of detoxification enzymes, cell proliferation, and apoptosis. GSH, GSH S-conjugates, and its disulfide form (GSSG), or the redox state of the GSH/GSSG couple provide a mechanistic control or signal for functional changes. A loss or oxidation of GSH occurs in association with differentiation both in vitro and in vivo and during apoptosis. In contrast, increases in GSH and/or a reduction of the GSH/GSSG pool is associated with growth stimulation by nutrients and growth factors. Thus, the balance of GSH and GSSG may not only reflect oxidative stress but may reflect changes in redox signaling and control. The most widely used indicator of the redox state of the GSH pool is the ratio of GSH to GSSG. The cellular balance of GSH and GSSG provides a dynamic indicator of oxidative stress. Although GSH is synthesized continuously and has various fates in cells, these rates are generally slow relative to the turnover by the oxidation-reduction cycle. The activity of the GSSG reductase is dependent on GSSG concentration. During acute oxidative stress, GSH concentration decreases and the associated increase in GSSG concentration results in an increased turnover of the GSH/GSSG cycle.
Using the 32P-postlabeling assay, we investigated the ability of quaternary benzo[c]phenanthridine alkaloids, sanguinarine, chelerythrine and fagaronine, to form DNA adducts in vitro. Two enhanced versions of the assay (enrichment by nuclease P1 and 1-butanol extraction) were utilized in the study. Hepatic microsomes of rats pre-treated with beta-naphthoflavone or those of uninduced rats, used as metabolic activators, were incubated in the presence of calf thymus DNA and the alkaloids, with NADPH used as a cofactor. Under these conditions sanguinarine and chelerythrine, but not fagaronine, formed DNA adducts detectable by 32P-postlabeling. DNA adduct formation by both alkaloids was found to be concentration dependent. When analyzing different atomic and bond indices of the C11-C12 bond (ring B) in alkaloid molecules we found that fagaronine behaved differently from sanguinarine and chelerythrine. While sanguinarine and chelerythrine showed a preference for electrophilic attack indicating higher potential to be activated by cytochrome P450, fagaronine exhibited a tendency for nucleophilic attack. Our results demonstrate that sanguinarine and chelerythrine are metabolized by hepatic microsomes to species, which generate DNA adducts.
A water-soluble (at pH 8) aromatic disulfide [5,5′-dithiobis(2-nitrobenzoic acid)] has been synthesized and shown to be useful for determination of sulfhydryl groups.Several applications have been made to show its usefulness for biological materials.A study of the reaction of this disulfide with blood has produced some evidence for the splitting of disulfide bonds by reduced heme.
Consumption of mustard oil adulterated with argemone oil leads to a clinical condition, commonly referred to as "Epidemic Dropsy." Since in vitro studies have shown that sanguinarine, an active benzophenanthridine alkaloid of argemone oil, intercalates DNA molecule, the in vivo clastogenic and DNA damaging potential of argemone oil was investigated in mice. Swiss albino mice were intraperitoneally administered 0.5, 1.0, 2.0 and 4.0 ml/kg body wt. of argemone oil to analyze chromosome aberrations and micronucleus test, while 0.25, 0.5, 1.0 and 2.0 ml/kg body wt. were given for alkaline comet assay. The frequencies of chromosomal aberrations and micronucleated erythrocytes formation in mouse bone marrow cells increased in a dose-dependent manner following argemone oil treatment. However, significant induction in chromosomal aberrations (83%) and micronucleated erythrocytes formation (261%) were observed at a minimum dose of 1.0 ml/kg. The results of comet assay revealed DNA damage in blood, bone marrow and liver cells following argemone oil treatment. Olive tail moment (OTM) and tail DNA showed significant increase in bone marrow (35-44%) and blood cells (25-40%) even at a dose of 0.25 ml/kg body wt. of argemone oil. In liver cells, OTM was significantly increased (20%) at a dose of 0.25 ml/kg, while all the comet parameters including OTM, tail length and tail DNA showed significant increase (31-101%) at a dose of 0.5 ml/kg. These results clearly suggest that single exposure of argemone oil even at low doses produces genotoxic effects in mice.
Consumption of mustard oil contaminated with argemone oil is well known to cause clinical manifestation referred to as "Epidemic Dropsy". Our prior studies have shown that argemone oil produces genotoxic effects in mice [Ansari, K.M., et al., 2004. Int. J. Cancer 112, 890]. Since, sanguinarine alkaloid is the major component of argemone oil, the in vivo DNA damaging potential of the isolated alkaloid was investigated in blood and bone marrow cells of mice using alkaline Comet assay. Swiss albino male mice were given single intraperitoneal administration of 1.35, 2.70, 5.40, 10.80 and 21.60 mg sanguinarine alkaloid/kg b wt., while controls were treated with saline in the same manner. The results revealed a dose dependent increase in DNA damage in blood and bone marrow cells following 24 h treatment of sanguinarine alkaloid. All the three parameters of Comet assay including olive tail moment (OTM), tail length and tail DNA showed significant (p<0.05) increases in blood and bone marrow cells at respective doses of 10.80 and 5.40 mg alkaloid/kg b wt. However, some of the parameters were significantly increased even at lower doses of sanguinarine alkaloid (2.70 mg/kg b wt.). The frequency of cells exhibiting greater DNA damage were found to be increased by sanguinarine alkaloid in a concentration dependent manner. These results indicate that single exposure of sanguinarine alkaloid causes DNA damage in blood and bone marrow cells of mice, which could be responsible for the genotoxicity of argemone oil.
Epidemic dropsy is an acute food adulterant disease caused due to consumption of edible mustard oil contaminated with argemone oil. Our in vitro studies have shown that the toxicity of argemone oil is due to the production of reactive oxygen species. The present study was aimed to evaluate the development of oxidative stress in terms of oxidation of plasma proteins and lipids and its correlation to enzymatic and non-enzymatic antioxidants in epidemic dropsy patients. Total plasma protein and globulin contents were found to be significantly (P<0.05) enhanced with a concomitant decrease (P<0.05) in albumin/globulin ratio in dropsy patients when compared to controls. Total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol were found to be significantly (P<0.05) increased with a simultaneous decrease (51%) in high density lipoprotein cholesterol in dropsy patients. The oxidation of plasma proteins and lipids were substantially enhanced (162-175%) in dropsy patients when compared to controls. Further, significant (P<0.05) decrease in superoxide dismutase, catalase, glutathione reductase and glutathione-s-transferase with a concomitant increase (69%) in glutathione peroxidase activity was noticed in dropsy patients. A significant reduction in plasma total antioxidant capacity, alpha-tocopherol, glutathione, retinol and retinyl esters content was observed in dropsy patients when compared to healthy controls. The results suggest that there exists an unproportionate equilibrium between free radicals formation and enzymatic and non-enzymatic antioxidant scavengers, which may cause oxidative damage to proteins and lipids in dropsy patients.
In recent times, a higher incidence of gall bladder carcinoma in the Indo-Gangetic basin has been linked with the consumption of contaminated mustard oil. Consumption of mustard oil contaminated with argemone oil (AO) is well known to cause clinical manifestation referred to as "epidemic dropsy." Because sanguinarine, an active alkaloid of AO, has been shown to intercalate DNA, a possible correlation of DNA damage in epidemic dropsy patients to tumorigenic potential of AO and isolated sanguinarine alkaloid in mice was investigated in the present study. Single topical application of AO (0.15-0.3 ml) or isolated sanguinarine (4.5-18 micromol) followed by twice-weekly application of tetradecanoylphorbolmyristate acetate (TPA) for 25 weeks resulted in formation of tumors. Histopathologically these tumors were of squamous cell carcinoma type and similar to those found in the positive control group using dimethylbenzanthracene (DMBA)/TPA. The activities of cutaneous gamma-glutamyl transpeptidase (GGT) and glutathione-S-transferase P (GST-P), marker enzymes of tumorigenesis, were found to exhibit higher expression in AO or isolated sanguinarine/TPA treated groups when compared to control. The higher expression of p53 and p21/WAF1 in skin after single topical application of AO or isolated sanguinarine further confirms the tumorigenic response. Single topical application of AO or isolated sanguinarine alkaloid to mice showed significant DNA damage in terms of Olive tail moment (89-129%), tail length (54%) and tail DNA (153-205%) using Comet assay in skin cells. Further, the extent of DNA damage in blood cells of epidemic dropsy patients in alkaline Comet assay was found to be significantly higher as compared to normal population, indicating the genotoxic response of AO exposure. Although the genotoxic lesions may be repaired to some extent on withdrawal of consumption of AO contaminated mustard oil and the residual genotoxic effects caused by AO may not be expressed as signs of carcinogenesis. Environmental factors or hormonal changes during aging process may lead to stimulate/promote the genetically altered latent cells to form neoplastic lesions and can act as one of the etiological factors responsible for higher incidence of gall bladder carcinoma in the population of Indo-Gangetic basin.
Several incidences of adverse effects on human health have been reported in many countries, due to consumption of edible oil adulterated with argemone oil (AO). The clinical manifestation of the disease is commonly referred to as epidemic dropsy. In the present study, we determined the relationship between redox potentials (E(h)) of glutathione/glutathione disulfide (GSH/GSSG), cysteine/cysteine disulfide (Cys/CySS) couples and non-enzymatic antioxidants such as alpha-tocopherol and ascorbic acid status in plasma of dropsy patients (n=14) from an outbreak of argemone oil poisoning in Lucknow (March, 2005), India. Depleted GSH (55%) and concomitant enhancement (163%) of plasma GSSG content was observed in patients (P<0.05). Furthermore, lower content of Cys (42%) and CySS (25%) was noticed in patients (P<0.05) when compared to control subjects. Eh GSH and Eh Cys values were shifted by +46 mV and +12 mV towards more oxidizing environment in patients (P<0.05). In addition, alpha-tocopherol and ascorbic acid contents were found to be depleted significantly (P<0.05) in plasma of patients (59-58%). The alterations in redox potentials and antioxidants in plasma, which are synthesized in liver, may be responsible for histopathological changes in hepatic tissue of patients showing swelling of hepatocytes, fluid accumulation in spaces of Desci along with mild kupfur cell hyperplasia. Over all the present study shows that redox state of GSH/GSSG and Cys/CySS pools become oxidized which inturn causes depletion of alpha-tocopherol and ascorbic acid, thus providing a strategy to distinguish pro-oxidant and antioxidant events in patients.
The quaternary benzo[c]phenanthridine alkaloid sanguinarine (SG) is the main component of Sangrovit, a natural livestock feed additive. Dihydrosanguinarine (DHSG) has recently been identified as a SG metabolite in rat. The conversion of SG to DHSG is a likely elimination pathway of SG in mammals. This study was conducted to evaluate the toxicity of DHSG in male Wistar rats at concentrations of 100 and 500 ppm DHSG in feed for 90 days (average doses of 14 and 58 mg DHSG/kg body weight/day). No significant alterations in body or organ weights, macroscopic details of organs, histopathology of liver, ileum, kidneys, tongue, heart or gingiva, clinical chemistry or hematology markers in blood in the DHSG-treated animals were found compared to controls. No lymphocyte DNA damage by Comet assay, formation of DNA adducts in liver by 32P-postlabeling, modulation of cytochrome P450 1A1/2 or changes in oxidative stress parameters were found. Thus, repeated dosing of DHSG for 90 days at up to 500 ppm in the diet (i.e. approximately 58 mg/kg/day) showed no evidence of toxicity in contrast to results published in the literature. In parallel, DHSG pharmacokinetics was studied in rat after oral doses 9.1 or 91 mg/kg body weight. The results showed that DHSG undergoes enterohepatic cycling with maximum concentration in plasma at the first or second hour following application. DHSG is cleared from the body relatively quickly (its plasma levels drop to zero after 12 or 18 h, respectively).
Report on the investigation of an outbreak in Rangoon in the year 1924
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The formation and reduction of methemoglobin in human erythrocytes. In: Cellular and Molecular Biology of Eryth-rocytes
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An epidemic of dropsy among Indians in Fiji
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Management of epidemic dropsy caused by argemone oil In: Health and Dietary Aspects of Mustard Oil
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