Article

The Role of Uric Acid as an Antioxidant in Selected Neurodegenerative Disease Pathogenesis: A Short Review

Authors:
To read the full-text of this research, you can request a copy directly from the author.

Abstract

Uric acid, a potent antioxidant for humans, birds, reptiles, and some primate species, is the end-product of purine degradation that is formed in the xanthine/hypoxanthine reactions catalyzed by xanthine oxidase. Associated with the evolutionary loss of urate oxidase (the enzyme that oxidizes uric acid resulting in the formation of allantoin) and resulting increase in concentrations of uric acid is a prolonged life span. Uric acid is known to scavenge peroxynitrite and other free radicals that can cause an imbalance of oxidants leading to oxidative stress. Uric acid also has a role in protecting DNA from single-strand breaks caused by free radicals in the body leading to a protective effect in neurodegenerative diseases. The brain is particularly vulnerable to oxidative stress as it is considered an ‘expensive tissue’ with a particularly high metabolic rate and comparatively increased utilization of oxygen. Brain tissue is also high in unsaturated lipids, which makes it more susceptible to free radical damage. Oxidative stress is thus linked to the pathogenesis of neurodegenerative diseases and also ischemic brain injury. In this review, we summarize the function of uric acid in alleviating oxidative damage and providing protection to neural cells during injury and disease.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the author.

... Differential alterations in serum metabolites were evident among the chicken ecotypes and between heat treatments in the current study. The reduction of serum uric acid in C could be an indication that the chickens had not yet recovered and were sliding into increased inflammation and oxidative stress (Settle & Klandorf, 2014). Conversely, the marked increase in K may be a demonstration of a stronger antioxidant response aimed at countering the effects of heat stress and low dietary energy. ...
... The differences in responses between the two treatment groups in the present study may also highlight the differences in metabolic rates and states, signifying protein catabolism for energy generation in energy restricted birds resulting from increased corticosterone levels (Virden et al., 2007). Uric acid is the metabolic product of purine metabolism and is an important plasma antioxidant in birds (Settle & Klandorf, 2014). ...
Article
Full-text available
Two experiments were conducted to compare effects of heat stress and its combination with low dietary energy on blood indices, liver hsp70 and iNOS gene expressions in three Tanzanian local chicken ecotypes. In experiment one, five weeks old Kuchi (K), Ching'wekwe (C) and Morogoro medium (M) were randomly allocated to separate pens in a 3 × 2 factorial design in two adjacent rooms with controlled temperature. The study had three replicates consisting of 39 chickens per room, 13 per ecotype per pen making a total of 234 chickens. In one room, temperature was maintained at 26.5±0.5°C while in another it was maintained at 32±1°C for 7 days and thereafter 37±1°C for 10 days. A similar design was used in experiment two except that chickens were fed 55% less energy. In experiment one, serum corticosterone levels increased (p<0.05) in C and K. Gene expressions for hsp70 and iNOS were unchanged though hsp70 levels for K were higher (p<0.05). In experiment two, corticosterone levels were significantly elevated (p<0.05) in all ecotypes. Heterophil/lymphocyte ratios were markedly increased and changes in Hb and Hct at higher temperatures showed ecotype differences. Serum triglycerides were significantly reduced in all ecotypes. Hsp70 and iNOS levels were up-regulated in all ecotypes with levels in K higher (p<0.05) than in M. In both experiments, there were marked reductions in serum total protein. These results suggest that ecotype-based differences exist in local chickens’ responses to heat stress and its combination with low energy diets. M and C demonstrated better tolerance than K when only heat stress was applied but a synergistic effect of heat stress and low dietary energy suggested M is more tolerant.
... This compound can be also found in the body of birds, reptiles and some primate species. The end product of purine degradation is found in all mentioned organisms (Settle and Klandorf 2014). Its antioxidant properties are associated mainly with its ability to scavenge peroxynitrite and other free radicals. ...
... Additionally, it is responsible for protecting DNA against single-strand breaks caused by reactive oxygen species. This role is of significant importance in the neurodegenerative diseases (Settle and Klandorf 2014). ...
Article
Full-text available
Oxidative stress, associated with an imbalance between the oxidants (reactive oxygen species) and the antioxidants in the body, contributes to the development of many diseases. The body’s fight against reactive oxygen species is supported by antioxidants. Nowadays, there are too many analytical methods, but there is no one universal technique for assessing antioxidant properties. Moreover, the applied different ways of expressing the results lead to their incompatibility and unreasonable interpretation. The paper is a literature review concerning the most frequent ways of antioxidant activities expression and for an easy and universal method of the obtained results discussion. This paper is an attempt to point out their disadvantages and advantages. The manuscript can support the searching interpretation of the obtained results which will be a good tool for the development of a number of fields, especially medicine what can help in the future detection and treatment of many serious diseases. Graphic abstract
... In another study, inosine adminstration to birds being treated with hemin (a prooxidant), showed elevation in UA concentrations and reduction in hemin-induced oxidative stress [42][43][44][45]. Aforementioned results strengthened the hypothesis of an inverse relationship between UA concentrations and oxidative stress [46]. ...
... Settle T and Hillar Klandorf supported the role of UA as an antioxidant in selected neurodegenerative diseases. In neurodegenerative diseases, UA plays an important part in protecting DNA from single-strand breaks caused by free radicals in the body [46]. There are multiple studies in human showing that UA may have a beneficial role in cancer [51] and nervous system diseases such as multiple sclerosis [52,53], amyotrophic lateral sclerosis [54], Parkinson's disease [55,56], Alzheimer's disease [57], and dementia [58]. ...
Article
Background and objective: Osteoporosis is a common bone disorder that increases susceptibility to fragility bone fractures. The clinical and public health repercussions of osteoporosis are huge due to the morbidity, mortality, and cost of medical care linked with fragility fractures. Clinical assessment of osteoporotic risk factors can help to identify candidates at an early stage that will benefit from medical intervention and potentially lowering the morbidity and mortality seen with fractures and complications. Given this, research is ongoing to evaluate the association of osteoporosis with some novel or less well-studied risk factors/bio-markers such as uric acid (UA). Discussion: Uric acid's antioxidant activity has been proposed to be one of the factors responsible for increasing longevity and lowering rates of age-related cancers during primate evolution, the level of which increased markedly due to loss of uricase enzyme activity (mutational silencing). Accumulated evidence shows that oxidative stress is the fundamental mechanism of age-related bone loss and acts via enhancing osteoclastic activity and increasing bone resorption. Antioxidant substances such as ascorbic acid scavenge free radicals and are positively related to bone health. Thus, it is hypothesized that uric acid holds bone-protective potential owing to its potent antioxidative property. Several correlation studies have been conducted globally to investigate the relationship between serum uric acid with bone mineral density and osteoporosis. Few pre-clinical studies have tried to investigate the interaction between uric acid and bone mineral density and reported important role played via Runt-related transcription factor 2 (RUNX2)/core-binding factor subunit alpha-1 (CBF-alpha-1), Wingless-related integration site (Wnt)-3a/β-catenin signaling pathway and 11β Hydroxysteroid Dehydrogenase type 1. Conclusion: In this review, the authors provided a comprehensive summary of the literature related to association studies reported in humans as well work done until date to understand the potential cellular and molecular mechanisms that interplay between uric acid and bone metabolism.
... Also, oxidative stress catalyzes both hypoxanthine's conversion to xanthine and, in turn, to uric acid [48]. Uric acid is a potent plasma antioxidant that scavenges singlet oxygen, peroxy radicals, and hydroxyl radicals and has been studied extensively in many physiological and pathological systems, including neurodegenerative diseases [49]. Consistent with findings of the study, results of which are reported here, previous studies have found exposure to AFB 1 caused harmful effects that cause depletion of the antioxidant defense system leading to oxidative stress and a reduction of amounts of GSH and activities of SOD and GST [50,51]. ...
Article
Full-text available
Attenuation of adverse effects of aflatoxin (AFB1) in brains of B1 rats by extracts of leaves of artichoke was studied. The active ingredients in extracts of leaves of artichoke, Cynara scolymus L., were determined by HPLC analysis. In the 42-day experiment, rats were exposed to either sterile water, 4% DMSO, 100 mg artichoke leaf extract/kg body mass, 72 μg aflatoxin B1/kg body mass, or AFB1 plus artichoke leaf extract. Neurotoxicity of AFB1 was determined by an increase in profile of lipids, augmentation of plasmatic glucose and concentrations of insulin, oxidative stress, increased activities of cholinergic enzymes, and a decrease in activities of several antioxidant enzymes and pathological changes in brain tissue. Extracts of artichoke leaf significantly reduced adverse effects caused by AFB1, rescuing most of the parameters to values similar to unexposed controls, which demonstrated that adverse, neurotoxic effects caused by aflatoxin B1 could be significantly reduced by simultaneous dietary supplementation with artichoke leaf extract, which itself is not toxic.
... On the other hand, low uric acid levels have been shown to decrease the activity of myeloperoxidase and increase lipid peroxidation through the loss of the antioxidant properties of uric acid (Becker et al., 2019). The reduced antioxidant capacity is believed to be neurotoxic due to increased oxidative damage (Fang et al., 2013), but it remains unclear if this loss is sufficient to induce neurodegenerative diseases (Settle, 2014). ...
Article
Full-text available
Hypouricaemia has received relatively little attention in the literature. As a result, there is less awareness or understanding of the potential risks of low uric acid levels. Emerging research indicates that normal uric acid levels may have an antioxidative and neuroprotective effect. This study aims to investigate possible associations between hypouricaemia and neurodegenerative disease. Data was collected from seventy-seven outpatients and inpatients who underwent routine uric acid testing, who were then stratified into patients with and without neurodegenerative disease. Patients with renal pathologies and patients using uric acid altering medications were excluded from the study. There was a significant difference in the prevalence of Alzheimer’s disease between hypouricemic and normouricemic patients (p = 0.001), however there was no difference in the prevalence of vascular dementia (p = 0.45). This study provides evidence that hypouricaemia has potential effects on health, specifically on the rate of neurodegenerative diseases such as Alzheimer’s disease and gives weight to the potential neuroprotective role of uric acid.
... Diğer memelilerden farklı olarak insanlarda ürikaz aktivitesi olmadığı için ürik asit, pürin katabolizmasının son ürünüdür 8 . Normal düzeylerde toksik reaktanları temizlediği, dokuyu oksidatif strese karşı koruduğu bildirilmektedir [9][10][11] . Hatta total plazma antioksidan kapasitesinin 2/3'ünden sorumlu olduğunu savunan çalışmalar bulunmaktadır. ...
Article
Purpose: The aim of this study was to determine the frequency of metabolic syndrome in obese patients and to evaluate serum uric acid levels in obese patients with metabolic syndrome. Materials and Methods: The retrospective study included 270 obese patients with follow-up at the Obesity Center of Health Sciences University Antalya Training and Research Hospital between November 2018 and February 2020. Patients who were divided into two groups with and without metabolic syndrome were compared in terms of serum uric acid levels. Results: Of the patients 92,6% were female and 7,4% were male. The average age was 51,8±9,6 years. 141 patients (52,22%) had metabolic syndrome. Weight, body mass indexe, waist/hip ratio were significantly higher in patients with metabolic syndrome. In addition to metabolic syndrome parameters, glycosylated hemoglobin, fasting insulin, insulin resistance and uric acid levels were also significantly higher in the group with metabolic syndrome. A statistically significant positive correlation was found between uric acid and waist circumference, fasting insulin and insulin resistance in patients with metabolic syndrome. Multivariate logistic regression analysis showed that uric acid increased the risk of metabolic syndrome regardless of other parameters. Conclusion: The frequency of metabolic syndrome increases in obese patients, and serum uric acid levels increase in obese patients accompanied by metabolic syndrome. In addition, there is a positive correlation between serum uric acid levels and waist circumference and insulin resistance in these patients. Especially obese patients with metabolic syndrome accompanying with abdominal obesity and insülin resistance should be screened for hyperuricemia, which is considered as a cardiovascular disease risk marker.
... Diğer memelilerden farklı olarak insanlarda ürikaz aktivitesi olmadığı için ürik asit, pürin katabolizmasının son ürünüdür 8 . Normal düzeylerde toksik reaktanları temizlediği, dokuyu oksidatif strese karşı koruduğu bildirilmektedir [9][10][11] . Hatta total plazma antioksidan kapasitesinin 2/3'ünden sorumlu olduğunu savunan çalışmalar bulunmaktadır. ...
Article
Purpose: The aim of this study was to determine the frequency of metabolic syndrome in obese patients and to evaluate serum uric acid levels in obese patients with metabolic syndrome. Materials and Methods: The retrospective study included 270 obese patients with follow-up at the Obesity Center of Health Sciences University Antalya Training and Research Hospital between November 2018 and February 2020. Patients who were divided into two groups with and without metabolic syndrome were compared in terms of serum uric acid levels. Results: Of the patients 92,6% were female and 7,4% were male. The average age was 51,8±9,6 years. 141 patients (52,22%) had metabolic syndrome. Weight, body mass indexe, waist/hip ratio were significantly higher in patients with metabolic syndrome. In addition to metabolic syndrome parameters, glycosylated hemoglobin, fasting insulin, insulin resistance and uric acid levels were also significantly higher in the group with metabolic syndrome. A statistically significant positive correlation was found between uric acid and waist circumference, fasting insulin and insulin resistance in patients with metabolic syndrome. Multivariate logistic regression analysis showed that uric acid increased the risk of metabolic syndrome regardless of other parameters. Conclusion: The frequency of metabolic syndrome increases in obese patients, and serum uric acid levels increase in obese patients accompanied by metabolic syndrome. In addition, there is a positive correlation between serum uric acid levels and waist circumference and insulin resistance in these patients. Especially obese patients with metabolic syndrome accompanying with abdominal obesity and insülin resistance should be screened for hyperuricemia, which is considered as a cardiovascular disease risk marker.
... Diğer memelilerden farklı olarak insanlarda ürikaz aktivitesi olmadığı için ürik asit, pürin katabolizmasının son ürünüdür 8 . Normal düzeylerde toksik reaktanları temizlediği, dokuyu oksidatif strese karşı koruduğu bildirilmektedir [9][10][11] . Hatta total plazma antioksidan kapasitesinin 2/3'ünden sorumlu olduğunu savunan çalışmalar bulunmaktadır. ...
Article
Amaç: Bu çalışmada; obez hastalarda metabolik sendrom görülme sıklığının belirlenmesi ve metabolik sendromlu obez hastalarda serum ürik asit düzeylerinin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: Retrospektif çalışmaya Kasım 2018-Şubat 2020 tarihleri arasında Sağlık Bilimleri Üniversitesi Antalya Eğitim ve Araştırma Hastanesi Obezite Merkezinde takipli 270 obez hasta dahil edildi. Metabolik sendrom olan ve olmayan şeklinde iki gruba ayrılan hastalar serum ürik asit düzeyleri ve diğer çalışma parametreleri açısından karşılaştırıldı. Bulgular: Hastaların %92,6’sı kadın, %7,4'ü erkekti. Ortalama yaş 51,8±9,6 (21–73) yıl idi. 141 hastada (%52,22) metabolik sendrom vardı. Metabolik sendrom olan hastalarda kilo, vücut kitle indeksi, bel/kalça oranı ölçümleri anlamlı yüksek bulundu. Metabolik sendrom parametrelerinin yanı sıra glikozillenmiş hemoglobin, açlık insülini, insülin direnci ve ürik asit düzeyleri de metabolik sendrom olan grupta anlamlı yüksekti. Metabolik sendromolan hastalarda ürik asit ile bel çevresi, açlık insülini ve insülin direnci arasında istatistiksel olarak anlamlı pozitif bir korelasyon saptandı. Çok değişkenli lojistik regresyon analizi; ürik asitin diğer parametrelerden bağımsız olarak metabolik sendrom riskini arttırdığını gösterdi. Sonuç: Obez hastalarda metabolik sendrom görülme sıklığı artmaktadır ve metabolik sendromun eşlik ettiği obez hastalarda serum ürik asit düzeyleri yükselmektedir. Ayrıca bu hastalarda serum ürik asit düzeyleri ile bel çevresi ve insülin direnci arasında pozitif korelasyon görülmektedir. Bu bağlamda, özellikle abdominal obezite ve insülin direnci tespit edilen metabolik sendromlu obez hastalar kardiyovasküler hastalık risk belirteci olarak değerlendirilen hiperürisemi açısından taranmalıdır.
... Diğer memelilerden farklı olarak insanlarda ürikaz aktivitesi olmadığı için ürik asit, pürin katabolizmasının son ürünüdür 8 . Normal düzeylerde toksik reaktanları temizlediği, dokuyu oksidatif strese karşı koruduğu bildirilmektedir [9][10][11] . Hatta total plazma antioksidan kapasitesinin 2/3'ünden sorumlu olduğunu savunan çalışmalar bulunmaktadır. ...
... Uric acid also plays an important role in the antioxidant defense of the body, because it has the ability to bind iron ions and react with oxidizing agents. Uric acid is considered to be the most important substance responsible for total antioxidant capacity of blood plasma [16], being a powerful scavenger of free radicals, and provides ∼60% of free-radical scavenging capacity in plasma [17]. ...
Article
Full-text available
The present work aims at accessing the stability of biological material stored for diagnostic and scientific purposes. The influence of the temperature, storage time, and cyclic thawing on concentration stability of selected oxidative stress parameters in human serum was investigated. The study group consisted of 20 serum samples collected from healthy volunteers aged 18–52. The parameters whose reference ranges were not determined and to which validated determination methods did not correspond were examined by manual methods (FRAP and AOPP). Automatic methods were used to determine routine laboratory tests (albumin, total protein, bilirubin, uric acid) using the Konelab 20i® analyzer. The samples were stored at various temperatures (room temperature, 4 °C, −20 °C, −80 °C) for max 6 months and were subjected to cyclic thawing at 1 month intervals. In order to check whether any differences between the concentrations of the studied parameters existed when the samples were stored in various conditions, the paired Student t-test or Wilcoxon test and comparison to desirable bias were applied. Based on the obtained results, it was found that the temperature and time of serum sample storage significantly affected the stability of the analyzed parameters and determined different shelf lives of serum samples for oxidative stress examination. Therefore, continuing the investigation concerning the impact of storage conditions on various serum parameters seems justified due to the discrepancy between the individual results obtained by different researchers and the inconsistencies between the results of scientific research and the applicable recommendations.
... As by-products ROS have a significant role in the increased vascular oxidative stress (Higgins et al., 2011). Uric acid may play a predictive role as an antioxidant by scavenger a free radical and a chelator of transitional metal ions which are converted to poorly reactive forms (Settle and Klandorf, 2014). This may explain why this insecticide decrease or prevent the effect of oxidative stress in the serum or plasma. ...
Article
Full-text available
Acetamiprid (ACP) is neonicotinoid insecticide and it is the most highly effective insecticides worldwide for crop protection and control fleas infesting in livestock and pet animals. It has potential toxicity to mammals and there is no clear data regards to hepatotoxicity, nephrotoxicity and oxidative stress at low doses. The present study aimed to investigate the acute toxicity of ACP as formulation toward male adult albino rats and evaluate the impact effect of repeated sub-lethal dose of ACP. The high dose equal 1/10 of estimated LD50 and the low dose approximately equivalent 1.5X of No Observed Adversed Effect Level (NOAEL) dose. The study concluded the examination of hepatotoxicity, nephrotoxicity and some parameters that covered oxidative stress. The results revealed that, ACP may not have such extensive effects as inducer to oxidative stress but may be induce synergism of the defense system to increase the antioxidant self-system. Moreover, the histopathological investigation revealed that the exposure to high dose of ACP led to destructive and severe effects on the kidney tissue but may be has moderate effects on the liver tissue. The low dose which equal approximately 1.5X of NOAEL led to slight effects on the liver tissue while the kidney tissue was still more affected by this insecticide. Finally, It seems that the ACP induces the adverse effect at the high dose level but the low dose level and short term exposure may not make adverse effect. So, it can be recommend to use this insecticide as long as using the recommended dose.
... The significantly elevated uric acid level in the chemical cohort compared to controls seems to corroborate the elevation in GGT as a response to toxic challenge. Uric acid is an endogenous antioxidant and its elevation may indicate an ongoing repair to DNA damage (Olinsk et al., 2007;Settle and Klandorf, 2014). Indeed, uric acid has been inversely correlated to 8-hydroxyl deoxyguanosine (8-OHdG), a marker of DNA damage (Yoshida, 2002;Dziamin, 2007). ...
Article
Full-text available
Mixed chemical toxicity including genotoxicity is currently a major concern in rapidly industrializing developing countries. Simple biomarkers remain a constraint. Gamma-glutamyl-transpeptidase (GGT), a precursor of glutathione, protects against chemical toxicity including genotoxic effects and may serve as a marker for pre-neoplastic lesion. The objective of the study was to determine a possible relationship between GGT, uric acid and the angiogenic agent copper (Cu) in mixed chemical exposure. Sixty-six individuals occupationally exposed to mixed chemicals, mean age 34.4 ± 1.27 years, classified into 3 groups based on duration of exposure as follows: 1-10, 11-20 and > 20 years respectively, were enrolled into the study. Twentyseven, age- and sex-matched apparently healthy, occupationally unexposed individuals served as controls. The results showed that serum GGT was higher but not significantly different in exposed participants compared with controls; while its levels varied significantly with duration of exposure across the exposure groups. Like GGT, uric acid was significantly higher in the exposed than in controls and both significantly positively correlated with duration of exposure. Copper was higher in the exposed than the unexposed controls and correlated positively with GGT but not significantly. This observed up-regulation of GGT and its positive correlation with uric acid levels may be a protective response against oxidative stress arising from or related to the depletion of thiol group; thus enhancing maintenance of GSH levels; and may serve as an inexpensive early biomarker of mutagenicity in mixed chemical exposure. © 2016 International Formulae Group. All rights reserved. Keywords: Gamma-glutamyl-transpeptidase, uric acid, mixed chemical exposure, genotoxicity, mutagenicity
... In turn, activation of these transcription factors can lead to the expression of genes coding for inflammatory cytokines and chemokines amongst other regulatory molecules. ROS are involved in a broad spectrum of diseases associated with chronic inflammation, neurodegenerative diseases, and some cancer mechanisms (Reuter et al., 2010;Settle and Klandorf, 2014). Induction of these chemokines and cytokines as well as nitric oxide synthase, the enzyme family responsible for the conversion of L-arginine and NADPH to nitric oxide (i.e., NO) and L-citrulline, have been reported to have a role in oxidative stress induced inflammation (Hussain and Harris, 2007). ...
Article
Full-text available
Birds have a remarkable longevity for their body size despite an increased body temperature, higher metabolic rate, and increased blood glucose concentrations compared to most mammals. As the end-product of purine degradation, uric acid (UA) is generated in the xanthine/hypoxanthine reactions catalyzed by xanthine oxidoreductase (XOR). In the first study, Cobb × Cobb broilers (n = 12; 4 weeks old) were separated into 2 treatments (n = 6); control (CON) and allopurinol (AL) 35 mg/kg BW (ALLO). The purpose of this study was to assess mitochondrial function in broiler chickens in response to potential oxidative stress generated from the administration of AL for 1 wk. There was a significant reduction in state 3 respiration (P = 0.01) and state 4 respiration (P = 0.007) in AL-treated birds compared to the controls. The purpose of the second study was to assess the effect of AL on gene expression of inflammatory cytokines interferon-γ (IFN)-γ, IL-1β, IL-6, and IL-12p35, as well as inducible nitric oxide synthase and XOR in liver tissue. Cobb × Cobb broilers were separated into two groups at 4 wk age (n = 10); CON and ALLO. After 1 wk AL treatment, half of the birds in each group (CON 1 and ALLO 1) were euthanized while the remaining birds continued on AL treatment for an additional week (CON 2 and ALLO 2). A significant increase in gene expression of XOR, IFN-γ, IL-1β, and IL-12p35 in ALLO 2 birds as compared to birds in CON 2 was detected. Liver UA content was significantly decreased in both ALLO 1(P = 0.003) and ALLO 2 (P = 0.012) birds when compared to CON 1 and CON 2, respectively. The AL reduced liver UA concentrations and increased expression of inflammatory cytokines. Additional studies are needed to determine if AL causes a direct effect on mitochondria or if mitochondrial dysfunction observed in liver mitochondria was due indirectly through increased oxidative stress or increased inflammation. © 2015 Poultry Science Association Inc.
Thesis
Full-text available
Article
Full-text available
Seeking for new effectual anticancer drugs is of great importance. In this study, a newly synthesized and well-characterized chromene derivative (ethyl 2-amino-4-phenyl-4Hbenzo( h)chromene-3-carboxylate) “C” was prepared. Molecular docking studies were done. The new compound “C” in compare to the natural parent Quercetin “Q,” as a wellknown natural chromene derivative with antioxidant and antitumor activities, were tested for their antitumor activity against Ehrlich ascites carcinoma (EAC)-bearing mice. Both reduced ascites volume, decreased viable EAC cells, and prolonged EAC-bearing mice life span. They normalized troponin, creatine kinase-MB, lactate dehydrogenase, and urea levels, reversed liver enzyme activities towards normal, and increased antioxidant levels while reduced tumor necrosis factor-alpha (TNF-α) levels. Compared to each other, the new synthetic derivative “C” showed stronger antineoplastic effects than the natural parent “Q” may via the anti-inflammatory activities. Therefore, the newly synthesized chromene derivative is more promising as a future antitumor candidate than the natural parent molecule “Quercetin.” Finally, our results encourage researchers to pay more attention to developing more novel natural-based derivatives that would be more beneficial as future therapeutics than their natural parents.
Chapter
The changing lifestyle of human beings has impacted health in number of ways. It is the main gateway for the pathogenesis of various diseases and increase in the serum uric acid (UA) level in human body is one them. Though, UA is one of the major antioxidants found in human body which plays a significant role in providing almost half antioxidant activity to the blood, some researchers also suggested that the increased levels of UA in plasma act like key players in combating numerous serious disorders such as cancer, ageing, depression, anxiety, among others, by managing excessive oxidative stress, the main culprit and one of the underlying causes for most of these life threatening disorders. However, experimental studies and evidences which clearly demonstrated the association between increased levels of UA and diseases such as gout, cardiovascular disorders, renal disorders and metabolic syndrome cannot be neglected. This fact explains the importance of concentration of UA, its optimum level and its significance as one of the most critical parameters to be associated with the pathogenesis of severe diseases. This chapter includes the detailed discussion of UA, its optimum levels in blood, mechanism of action, risk factors associated with increased concentration of uric acid and studies conducted to elucidate the risks of UA.
Article
Full-text available
Cancer remains a global threat resulting in significant morbidity and mortality despite advances in therapeutic interventions, suggesting urgency for identification of anticancer agents. Crocodiles thrive in polluted habitat, feed on germ-infested meat, are exposed to carcinogenic heavy metals, are the very few species to survive the catastrophic Cretaceous–Paleogene extinction event, yet have a prolonged lifespan and rarely been reported to develop cancer. Therefore, we hypothesized that animals living in polluted environments such as crocodiles possess anticancer molecules/mechanisms. Crocodylus porosus was procured, blood collected, dissected and lysates prepared from internal organs. Organ lysates and sera were tested for growth inhibition, cytotoxic effects and cell survival against HeLa, PC3 and MCF7 cells and subjected to liquid chromatography mass spectrometry. RNA transcriptome analysis and differential gene analysis were performed using Galaxy Bioinformatics. Sera exhibited potent growth inhibition and cytotoxic effects against cancer cells. 80 molecules were detected from C. porosus and 19 molecules were putatively identified. Additionally, more than 100 potential anticancer peptides were identified from sera using bioinformatics based on peptide amino acid composition, binary profile, dipeptide composition and pseudo-amino acid composition. Following transcriptome analysis, 14 genes in treated HeLa cells, 51 genes in treated MCF7 cells and 2 genes in treated PC3 cells, were found to be expressed, compared with untreated controls. Animals residing in polluted milieus are an unexploited source for prospective pharmaceutical drugs, and could lead to identification of novel antitumour compound(s) and/or further understanding of the mechanisms of cancer resistance.
Article
This study examined the influence of a diet enriched with free methionine (dl-Met) or methionine dipeptide (dl-MMet) on the intestinal health of Eimeria-challenged (EC) and unchallenged (UC) broilers. A non-supplemented, methionine-deficient diet (NS) was used as control. Treatments were arranged in a 2 × 3 factorial completely randomized design with eight replications. Broilers in the EC group were infected with sporulated oocysts of Eimeria spp. (E. acervulina, E. maxima, E. praecox, and E. mitis) at 14 days of age. Performance analysis, light and electron microscopy of the jejunum, analysis of genes related to apoptosis and cell proliferation in the jejunum, and blood tests were performed at 6 days post-inoculation (dpi). EC broilers had poorer performance than UC broilers, regardless of diet (P < 0.001). Broilers fed the dl-Met diet had greater weight gain (P = 0.004) and lower feed conversion ratio (P = 0.019) than broilers fed other diets. Jejunal sections from EC broilers fed the NS diet showed short (P = 0.001) and wide villi (P < 0.001) with increased crypt depth (P < 0.001) and reduced villus / crypt ratio (P = 0.001), jejunal absorptive surface area (P < 0.001), number of neutral goblet cells (Eimeria challenge: P = 0.048; diet P = 0.016), and mucin 2 (MUC2) gene expression (P = 0.018). EC birds fed the dl-MMet diet had higher enterocyte height (P < 0.001). Birds fed the dl-MMet diet had low lamina propria width (P = 0.009). UC broilers fed the dl-Met diet had the highest number of acidic goblet cells (P = 0.005), whereas EC broilers assigned the dl-MMet diet showed the highest number of intraepithelial lymphocytes (P = 0.033). Reduced expression of caspase-3 (CASP3) (P = 0.005), B-cell lymphoma 2 (BCL2) (P < 0.001), mechanistic target of rapamycin (MTOR) (P < 0.001), and ribosomal protein S6 kinase B1 (RPS6KB1) (P < 0.001) genes was observed in EC animals. MTOR expression levels were highest in birds fed the dl-MMet diet (P = 0.004). Plasma activities of aspartate aminotransferase (AST) was influenced by both diet (P = 0.002) and Eimeria challenge (P = 0.005), with EC broilers assigned the NS diet showing the highest levels. EC broilers fed the NS diet had higher creatine kinase (CK) activity (P = 0.049). EC broilers had lower plasma uric acid (P = 0.004) and higher serum mucoproteins level (P < 0.001). These results indicate that methionine dipeptide supplementation is able to mitigate the harmful intestinal effects of Eimeria spp. in broilers.
ResearchGate has not been able to resolve any references for this publication.