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Natural sources of lipoic acid: Determination of lipoyllysine released from protease-digested tissues by high performance liquid chromatography incorporating electrochemical detection

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Abstract

The levels of lipoic acid in plant and animal tissues were determined in the form of lipoyllysine. After the hydrolysis of samples with proteases, the liberated lipoyllysine was extracted with ethanol and measured with high performance liquid chromatography (HPLC) equipped with an electrochemical detection system. The released lipoyllysine was confirmed both by spiking with synthesized lipoyllysine and by analyzing the molecular ion peak of lipoyllysine collected from HPLC samples by mass spectroscopy. Recovery tests of lipoyllysine bound to BSA showed 100% recovery within the calibration range used (0-2.5 μg/g) with this new method. Although our values are accurate, they may represent an underestimate since some lipoyllysine may remain inaccessible to protease digestion. The highest concentration of lipolylysine in the bovine tissues tested was found in the kidney, heart and liver, whilst in plant sources the highest was found in 'green' tissues such as spinach and broccoli. This may be a consequence of the increased number of chloroplasts which contain lipoyl domains. The lipoic acid content may then correlate with the metabolic activity of the tissues.

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... Current evidence indicates that several diet components have beneficial effects on obesity by affecting BAT and energy metabolism, including capsaicin and capsinoids, catechins, curcumin, quercetin, polyunsaturated fatty acid (PUFA), berberine, lipoic acid, royal jelly, and natural sweeteners. The food sources [25][26][27][28][29][30][31][32][33][34][35] and function of the potential BAT promoters above are shown in Table 1. ...
... Lipoic acid is the conjugate acid of lipoate, a cofactor of many mitochondrial enzymes usually binding to lysine in proteins. 33 It is found in green vegetables, organ meats and yeast. 33,34 RCTs demonstrate that lipoic acid has a lowering effect on body weight. ...
... 33 It is found in green vegetables, organ meats and yeast. 33,34 RCTs demonstrate that lipoic acid has a lowering effect on body weight. 75,76 Animal study by Tajima et al. indicates that supplementation of lipoic acid can restore BAT thermogenesis and improve ageassociated obesity in old mice without influencing BATspecific thermogenic genes expression (such as UCP1), and the mechanism is that lipoic acid increases mitochondrial lipoylation and then enzymatic activity of pyruvate dehydrogenase (PDH) by enhancing the Bola3-dependent mitochondrial iron-sulfur (Fe-S) cluster formation pathway. ...
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Background and objectives: Obesity is caused by excessive fat accumulation or abnormal fat distribution and has become one of the biggest health challenges worldwide. Considering the high thermogenic ability of brown fat tissue (BAT) and the plasticity of fat tissue, to induce the browning of white fat tissue (WAT), so increasing BAT activity provides an attractive option for the prevention and resolution of obesity. The aim of the present narrative review was to understand the relationship between diet, BAT, and obesity. Methods and study design: PubMed and Embase databases were searched to identify eligible studies. Results: Although cold exposure has long been known to be effective in the browning of WAT and activation of BAT, it is societally impractical for everyday body weight management aside from the tolerance of ambient temperature. An alternative is to identify specific dietary components with similar effects to cold exposure on BAT. Current evidence indicates that capsaicin and capsinoids, catechins, curcumin, quercetin, berberine, lipoic acid, polyunsaturated fatty acids, royal jelly, and some natural sweeteners are effective promoters of WAT browning, increase BAT activity and improve obesity related traits. However, only capsaicin, capsinoids, and catechins have demonstrated efficacy in clinical trials. Evidence for effects of curcumin, quercetin, berberine, lipoic acid, polyunsaturated fatty acids, royal jelly and natural sweeteners on BAT have only been observed in animal or in vitro studies, with clinical trials awaited for verification. Conclusions: Several dietary components can induce WAT browning and activate BAT, offering potential targets for obesity prevention and management.
... Therefore, this results in low recoveries because LA can experience considerable decomposition There are several methods for LA or LLys quantification in biological tissues (Table 1), which include the colorimetric assay, 16 an enzymatic method, 17,18 gas chromatography, 19−23 and high performance liquid chromatography (HPLC). 15,24,25 However, only three HPLC methods, based on ultraviolet, 24 electrochemical, 25 and fluorescence detections, 15 have been developed in recent years. Although these methodologies appear to be appropriate for the detection of LLys, the utility in biological samples is not sufficient enough in terms of selectivity and sensitivity. ...
... Therefore, this results in low recoveries because LA can experience considerable decomposition There are several methods for LA or LLys quantification in biological tissues (Table 1), which include the colorimetric assay, 16 an enzymatic method, 17,18 gas chromatography, 19−23 and high performance liquid chromatography (HPLC). 15,24,25 However, only three HPLC methods, based on ultraviolet, 24 electrochemical, 25 and fluorescence detections, 15 have been developed in recent years. Although these methodologies appear to be appropriate for the detection of LLys, the utility in biological samples is not sufficient enough in terms of selectivity and sensitivity. ...
... We observed some differences in the LLys concentrations found in tissue samples examined using the present method and other previously reported methods. 17,25 This discrepancy may be due to the physical state of the sample (e.g., fresh sample or acetone powder), the animal species (e.g., bovine, calves, pigs, chicken, and turkey), and differences in nutrition, age, sex, and, primarily, the methods used (e.g., enzymatic, GC, ECD). The LLys contents in bovine tissue acetone powders by the HPLC-ECD method 25 were determined for kidney, heart, and liver tissues and were from 0.86 to 2.64 μg/g. ...
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During this research a simple, accurate and environmental-friendly method to determine lipoyllysine and lipoic acid in meat was developed and validated. The presented approach was based on hydrolysis of the proteins containing lipoic acid, reduction of disulfide bonds with tris(hydroxymethyl)phosphine and pre-column derivatization of free thiol groups with 1-benzyl-2-chloropyridinium bromide,long-term followed by HPLC separation with a diode-array detector. The method has been validated in accordance with the US FDA guidelines and was linear in the range of concentrations 0.1-10 µmol/L with R2 values ≥ 0.9997 for both analytes. For lipoyllysine and lipoic acid intra- and inter-day precision values were lower than 10%. The intra-day accuracy values ranged from 91.0% to 99.4% for lipoyllysine and from 99.1% to 107.3% for lipoic acid, whereas the inter-day accuracy values for lipoyllysine and lipoic acid were 92.0-95.6% and 93.5-98.8%, respectively. Additionally, in this research an antioxidant activity of lipoyllysine and reduced lipoyllysine compound using spectrophotometric method with 1,1-diphenyl-2-picrylhydrazyl was examined for the first time. The data showed that dihydrolipoyllysine exhibits stronger antioxidant capacity than lipoyllysine based on lower value of concentration required to achieve a 50% antioxidant effect in 1,1-diphenyl-2-picrylhydrazyl radical scavenging test.
... It is worth mentioning that only the R isomer occurs naturally and the S isomer uprises in the chemical reactions [245][246][247]. Alpa-lipoic acid is produced by humans from fatty acids and cysteine, but its endogenous production is not sufficient to ensure the proper functioning of cells, which means that this compound is supplied to the body mainly through the diet [247,248]. Both animal and plant tissues contain alpha-lipoic acid in the form of the R isomer andit occurs in a form bound to lysine residues, as lipoyllysine. ...
... Both animal and plant tissues contain alpha-lipoic acid in the form of the R isomer andit occurs in a form bound to lysine residues, as lipoyllysine. The sources in which R-ALA occurs in the highest concentration in animal tissues are kidneys, heart and liver, while in plant sources R-ALA is found in the highest concentration in spinach, broccoli and tomatoes [246,248]. Alpha-lipoic acid available as a dietary supplement is a mixture of both racemic forms. Both ALA and its reduced form, dihydrolipoic acid (DHLA), have antioxidant properties and these forms arecalled together as "universal antioxidant" [246]. ...
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In order for the body to function properly, it needs not only food, but also nutrients and non-nutritive bioactive compounds that have an immunomodulating effect. This applies not only to healthy people, but especially to people with accompanying chronic diseases, including type 2 diabetes. Unfortunately, the current food industry and the use of highly processed food promote nutritional deficiencies. Many studies confirm their occurrence in patients with type 2 diabetes. The article presents the influence of selected nutrients on the functioning of the immune system, which ensures homeostasis of the body, with particular emphasis on type 2 diabetes. The role of macroelements, microelements, vitamins and selected substances, such as omega-3 acids, coenzyme Q10 and alpha-lipoic acid. The minimum scope of tests that should be performed in patients to directly or indirectly determine the degree of malnutrition in this group of patients is presented.
... It is an essential cofactor for several key enzymes, making it an indispensable part of the metabolic process in mitochondria (16). Additionally, ALA is a powerful antioxidant found in a wide variety of plant foods (17). Numerous experimental and clinical studies have revealed that ALA has powerful antioxidant and anti-in ammatory properties, making it a popular choice for preventing and treating various diseases (16,(18)(19)(20). ...
... ALA, a dietary supplement found naturally in spinach, broccoli, potatoes, tomatoes, and red meat (17), has been found to have a bioavailability of approximately 30% (33). Research conducted on animals and humans has indicated that consumption of ALA supplements in the short term has no signi cant adverse effects (18,34). ...
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This study aimed to investigate whether a combination of two potent antioxidants, alpha-lipoic acid (ALA) and mitoquinone (Mito Q), could improve myocardial function and the underlying mechanisms in an experimental model of myocardial infarction in aged rats. To develop a myocardial infarction model in aged rats the left anterior descending artery (LADA) was transiently occluded for 30 minutes and then re-perfused for 24 hours. Mito Q (10 mg/kg, IP) and ALA (100 mg/kg, gavage) was given daily for 2 weeks before occlusion of LADA. Subsequently, 24 hours after ischemia, left ventricular function was measured, and inflammatory factors (IL-6, IL-1β, TNF-α), tissue apoptosis, expression of Bax, Bcl-2, cytochrome C (Cyt-c), and caspase-3 were evaluated using ELISA, TUNEL, real-time PCR methods, respectively. The findings of this study indicated that the administration of the combination of ALA and Mito Q significantly improved cardiac function. This improvement was linked to a reduction in the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β (P < 0.001) and apoptotic markers (Bax, caspase-3, and Cyt-c), as well as a decrease in the percentage of TUNEL-positive cells (P < 0.001). The combined administration of ALA and Mito Q was found to synergistically reduce cardiac dysfunction in aged rats with myocardial infarction by inhibiting both the inflammatory and apoptotic pathways. This compound may offer a promising solution for elderly individuals who are at risk of heart attack, however, further research is needed to validate its potential
... The highest contents of lipoyllysine in animal products were found in bovine kidney, heart and liver while spinach and broccoli were the best of the investigated plant sources. Tests with lipoyllysine bound to BSA gave about 100% recovery (Lodge et al., 1997) indicating quantitative cleavage of the linkage to the protein. Another method based on enzymatic hydrolysis (Satoh, Shindoh, & Min, 2008) included liberation of lipoyllysine with several proteases, reduction of disulphide bond, labelling with a fluorophore and analysis by HPLC with fluorescence detection. ...
... Applying strong acid or alkaline conditions to release a-LA from the sample results in low recoveries because a-LA is partly destroyed. Likewise, evidence exists that the content of lipoyllysine determined by mild enzymatic hydrolysis may be underestimated because some lipoyllysine may remain inaccessible to protease digestion (Lodge et al., 1997). Nevertheless, the papers mentioned above offer the possibility to approximately determine the sum of free plus protein-bound lipoic acid, and the content of protein-bound lipoic acid by means of lipoyllysine, respectively. ...
Article
A simple and rapid method for determination of free alpha-lipoic acid in different food matrices has been developed. It consists of extraction of alpha-lipoic acid with 0.5% glacial acetic acid in methanol by sonication, quantitative analysis of the extract by isocratic RP-HPLC (acetonitrile/methanol/ 50 mM potassium dihydrogen phosphate buffer adjusted to pH 3 with phosphoric acid 350/65/585, v:v:v) at a flow rate of 0.45 ml/min coupled with coulometric electrode array at potentials between +300 and +700 mV and qualitative analysis by LC-ESI-MS in the negative ion mode for confirmation. Egg, dried egg powder, mayonnaise, fine peas and potatoes were analyzed and free alpha-lipoic acid contents ranged from 0.1 to 4.2 µg/g with recoveries between 70 and 94%. Limits of quantitation were between 0.1 and 0.3 µg/g. This newly developed method can be used to establish a database for the content of free alpha-lipoic acid in different foodstuffs.
... The highest contents of lipoyllysine in animal products were found in bovine kidney, heart and liver while spinach and broccoli were the best of the investigated plant sources. Tests with lipoyllysine bound to BSA gave about 100% recovery (Lodge et al., 1997) indicating quantitative cleavage of the linkage to the protein. Another method based on enzymatic hydrolysis (Satoh, Shindoh, & Min, 2008) included liberation of lipoyllysine with several proteases, reduction of disulphide bond, labelling with a fluorophore and analysis by HPLC with fluorescence detection. ...
... Applying strong acid or alkaline conditions to release a-LA from the sample results in low recoveries because a-LA is partly destroyed. Likewise, evidence exists that the content of lipoyllysine determined by mild enzymatic hydrolysis may be underestimated because some lipoyllysine may remain inaccessible to protease digestion (Lodge et al., 1997). Nevertheless, the papers mentioned above offer the possibility to approximately determine the sum of free plus protein-bound lipoic acid, and the content of protein-bound lipoic acid by means of lipoyllysine, respectively. ...
Article
A simple and rapid method for determination of free α-lipoic acid in different food matrices has been developed. It consists of extraction of α-lipoic acid with 0.5% glacial acetic acid in methanol by sonication, quantitative analysis of the extract by isocratic RP-HPLC (acetonitrile/methanol/50 mM potassium dihydrogen phosphate buffer adjusted to pH 3 with phosphoric acid: 350/65/585, v:v:v) at a flow rate of 0.45 ml/min coupled with coulometric electrode array detection at potentials between +300 and +700 mV and qualitative analysis by LC–ESI-MS in the negative ion mode for confirmation. Egg, dried egg powder, mayonnaise, fine peas and potatoes were analysed and free α-lipoic acid contents ranged from 0.1 to 4.2 μg/g with recoveries between 70% and 94%. Limits of quantitation were between 0.1 and 0.3 μg/g. This newly developed method can be used to establish a database for the content of free α-lipoic acid in different foodstuffs.
... ALA is abundantly present in vegetables and animal tissues [17], is promptly bioavailable, and has no known toxic effects on animals and human subjects [18]. Common dietary sources of ALA are meat, kidney, and liver, as well as fruits and vegetables, but the dietary intake is probably negligible; ALA absorption is in competition with other nutrients and generally is higher when assumed as a food supplement in the form of sodic salt [19]. ...
Article
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Background: Memory disorders are common among elder people, and nonclinical cognitive decline is commonly experienced with age. Preclinical investigations have explored the possible role of alpha-lipoic acid (ALA), a known antioxidant compound abundant in vegetables and animal tissues, in reducing oxidative stress in the aging brain and preventing cognitive decline. However, clinical evidence is limited, and the few existing results are contrasting. In addition, while most of the existing trials have been focused on the effects of ALA administration in Alzheimer's disease (AD) or other types of dementia, studies evaluating its effects on nonclinical elder population are still missing. Methods: In the present open-label, pilot study, fifteen elder patients (mean age: 84.5 ± 5.77) received ALA at a daily dose of 600 mg/day for 12 weeks. General cognitive function, executive function, and mood symptom assessment were carried out at baseline and at the endpoint. Results: Overall, ALA administration was generally well-tolerated (only one dropout due to gastrointestinal side effects). However, no statistically significant effects either on cognitive function, executive function, or mood were found. Conclusions: Despite several limitations, our study found no evidence of positive effects on cognition and mood after ALA administration in elder people without the diagnosis of AD or cognitive impairment. Further clinical trials are needed to better investigate ALA effectiveness on cognition and mood in elder subjects.
... α-LA jest przyswajany z pożywienia głównie w postaci lipolizyny. Największą zawartość tego związku wykazano w szpinaku, brokułach, pomidorach i podrobach [9]. α-LA jest związkiem rozpuszczalnym zarówno w wodzie, jak i w tłuszczach, dzięki czemu może dotrzeć do większości tkanek organizmu [10]. ...
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Kwas α-liponowy (α-LA) jest naturalnym antyoksydantem występującym w żywności w postaci lipolizyny. Zarówno α-LA, jak i jego zredukowana postać DHLA (kwas dihydroliponowy) hamują produkcję reaktywnych form tlenu (ROS) i redukują szkodliwe ich działanie, mają zdolność chelatowania jonów metali przejściowych oraz regeneracji innych przeciwutleniaczy. Oprócz efektu antyoksydacyjnego wykazują także działanie przeciwzapalne. Stres oksydacyjny i stan zapalny odgrywają kluczową rolę w patogenezie miażdżycy i chorób sercowo-naczyniowych. α-LA obniża poziom lipidów we krwi, zapobiega oksydacyjnym modyfikacjom cząsteczki LDL i hamuje tworzenie blaszki miażdżycowej. Jądrowy czynnik transkrypcyjny kappa B (NF-κB) przyczynia się do rozwoju miażdżycy poprzez aktywację genów prozapalnych, natomiast α-LA hamuje odpowiedź zapalną indukowaną przez NF-κB poprzez redukcję stresu oksydacyjnego, hamowanie ekspresji cząsteczek adhezyjnych oraz proliferacji i migracji komórek mięśni gładkich naczyń. Ponadto, suplementacja α-LA może obniżać ciśnienie krwi. W pracy dokonano przeglądu badań dotyczących roli α-LA w patogenezie miażdżycy i chorób sercowo-naczyniowych.
... during fatty acid synthesis, α-lipoic acid is synthesized in the mitochondria from octanoic acid, which binds to the acyl-carrier protein (19). in food sources, α-lipoic acid is present in the form of lipoyllysine, a lipoic acid covalently bound to lysine in proteins. lipoyllysine-rich animal tissues include the heart, kidneys, and liver, while broccoli and spinach are vegetables enriched in lipoyllysine (20). consumption of lipoyllysine-rich food does not increase plasma levels of free lipoic acid (21,22). ...
Article
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Cerulein‑induced pancreatitis resembles human acute pancreatitis in terms of pathological events, such as enzymatic activation and inflammatory cell infiltration in the pancreas. Cerulein is a cholecystokinin analog that increases levels of reactive oxygen species (ROS) and interleukin‑6 (IL‑6) expression level in pancreatic acinar cells. Serum levels of resistin, which is secreted from adipocytes, are reportedly higher in patients with acute pancreatitis than in healthy individuals. Previously, it was shown that the adipokine resistin can aggravate the cerulein‑induced increase in ROS levels and IL‑6 expression level in pancreatic acinar cells. Peroxisome proliferator‑activated receptor‑gamma (PPAR‑γ) is a key regulator of the transcription and expression of antioxidant enzymes, including heme oxygenase 1 (HO‑1) and catalase. α‑lipoic acid, a naturally occurring dithiol antioxidant, can prevent cerulein‑induced pancreatic damage in rats. In the present study, it was aimed to investigate whether α‑lipoic acid can attenuate the cerulein/resistin‑induced increase in IL‑6 expression and ROS levels via PPAR‑γ activation in pancreatic acinar AR42J cells. The anti‑inflammatory mechanism of α‑lipoic acid was determined using reverse transcription‑quantitative PCR, western blot analysis, enzyme‑linked immunosorbent assay, immunofluorescence staining and fluorometry. Treatment with cerulein and resistin increased ROS levels and IL‑6 expression level, which were inhibited by α‑lipoic acid in pancreatic acinar cells. α‑lipoic acid increased the nuclear translocation and expression level of PPAR‑γ and the expression levels of its target genes: HO‑1 and catalase. The PPAR‑γ antagonist GW9662 and HO‑1 inhibitor zinc protoporphyrin reversed the inhibitory effect of α‑lipoic acid on cerulein/resistin‑induced increase in ROS and IL‑6 levels. In conclusion, α‑lipoic acid inhibits the cerulein/resistin‑induced increase in ROS production and IL‑6 expression levels by activating PPAR‑γ and inducing the expression of HO‑1 and catalase in pancreatic acinar cells.
... Nevertheless, the amount of this antioxidant synthesized by the organism does not meet bodily needs [39] unless supplementarily administered through diet. In addition, ALA presents a low half-life and bioavailability due to hepatic degradation, reduced solubility, and instability in the stomach environment [40]. ...
Article
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The addition of the antioxidant α-lipoic acid (ALA) to a balanced diet might be crucial for the prevention of comorbidities such as cardiovascular diseases, diabetes, and obesity. Due to its low half-life and instability under stomach-like conditions, α-lipoic acid was encapsulated into chitosan nanoparticles (Ch-NPs). The resulting chitosan nanoparticles containing 20% w/w ALA (Ch-ALA-NPs) with an average diameter of 44 nm demonstrated antioxidant activity and stability under stomach-like conditions for up to 3 h. Furthermore, fluorescent Ch-ALA-NPs were effectively internalized into 3T3-L1 fibroblasts and were able to cross the intestinal barrier, as evidenced by everted intestine in vitro experiments. Thus, chitosan-based nanoparticles seem to be an attractive administration method for antioxidants, or other sensible additives, in food.
... Vegetable and animal tissues contain low amounts of R-(+)-LA detected in the form of lipoyllysine (attachment of LA to specific lysine residues) [20]. The most abundant vegetable sources of R-LA are spinach, broccoli, and tomatoes, which contain 3.2, 0.9, and 0.6 × 10 −3 g lipoyllysine/g dry weight, respectively. ...
... Afterwards, LA was confirmed as a vital cofactor of several enzymes (the pyruvate dehydrogenase complex, the α-ketoglutarate dehydrogenase complex, the branched-chain α-ketoacid dehydrogenase complex, the 2-oxoadipate dehydrogenase complex, and the glycine cleavage system) necessary for aerobic metabolism in mitochondria and the synthesis of nucleic acids [10]. Its natural molecule of (R)-(+)-enantiomer is mostly present in the form of combining with lysine residues of proteins in a wide variety of foods of plants (e.g., spinach and broccoli) and animals (e.g., kidney, heart, and liver) [11]. Free LA is mainly from chemical synthesis, which produced two enantiomers (R)-(+)-LA and (S)-(-)-LA. ...
Article
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Ischemia-reperfusion (I/R) injury often occurred in some pathologies and surgeries. I/R injury not only harmed to physiological functions of corresponding organ and tissue but also induced multiple tissue or organ dysfunctions (even these in distant locations). Although the reperfusion of blood attenuated I/R injury to a certain degree, the risk of secondary damages was difficult to be controlled and it even caused failures of these tissues and organs. Lipoic acid (LA), as an endogenous active substance and a functional agent in food, owns better safety and effects in our body (e.g., enhancing antioxidant activity, improving cognition and dementia, controlling weight, and preventing multiple sclerosis, diabetes complication, and cancer). The literature searching was conducted in PubMed, Embase, Cochrane Library, Web of Science, and SCOPUS from inception to 20 May 2021. It had showed that endogenous LA was exhausted in the process of I/R, which further aggravated I/R injury. Thus, supplements with LA timely (especially pretreatments) may be the prospective way to prevent I/R injury. Recently, studies had demonstrated that LA supplements significantly attenuated I/R injuries of many organs, though clinic investigations were short at present. Hence, it was urgent to summarize these progresses about the effects of LA on different I/R organs as well as the potential mechanisms, which would enlighten further investigations and prepare for clinic applications in the future.
... In addition, the increase in type IV and this collagen, IL-6, MCP-1, TGF and the macrophage marker CD68 was reduced. The researchers concluded that omega-3 polyunsaturated fatty acids significantly reduce kidney damage caused by diabetes [78]. ...
Article
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Diabetic nephropathy (DN), a fatal diabetic complication, is a prime reason of end-stage renal disease (ESRD), which is pathologically identified by thickened tubular basal and glomerular membranes, amassed extracellular matrix (ECM), and developing meningeal hypertrophy. Various deformities in the signaling pathway can interact to give rise to these pathologic activities in DN. In spite of the accessibility of numerous approaches to prevent these metabolic changes which include proper diet, exercising regularly, control of weight and control of drugs, epidemiological data are observing the growing tendency of the complication, indicating both the multifactorial nature of these disorders as well as the scarce conformance of patients to begin strategies. A number of Nutraceuticals utilized in clinical practice were shown to aim the pathophysiology of diabetes mellitus, metabolic disorder and their complications and to favorably modify numerous biochemical and clinical endpoints. These compounds comprise of antioxidants, vitamins like vitamin C, E, D; Omega 3 fatty acids, alpha lipoic acid (ALA), dietary fibers, flavonoids, phytoestrogens and minerals like chromium, magnesium. Various areas of concern prevail with regard of the use of nutraceuticals and dietary supplements in this setting, inclusive of standardization of products, potential side effects, definition of dosing regimen, interaction of drugs and need for evidence based interactions.
... Alpha lipoic acid (LA) is a disulfide free-radical scavenger found normally in mitochondria as the coenzyme for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. Studies have reported that the most abundant vegetable sources of lipoic acid are spinach, broccoli and tomatoes, which contain 3.2, 0.9 and 0.6 × 10 −1 g lipolyzing/g dry weight, respectively [15,16]. After dietary assimilation, LA is transported into cells and reduced to dihydrolipoic acid (DHLA), which has preeminent antioxidant activity [16]. ...
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Evidence suggests that oxidative stress plays a major role in the development of metabolic syndrome. This study aims to investigate whether α-lipoic acid (LA), a potent antioxidant, could exert beneficial outcomes in Zucker diabetic fatty (ZDF) rats. Male 6-week-old ZDF rats and their lean counterparts (ZL) were fed for six weeks with a standard diet or a chow diet supplemented with LA (1 g/kg feed). At 12 weeks of age, ZDF rats exhibited an increase in systolic blood pressure, epididymal fat weight per body weight, hyperglycemia, hyperinsulinemia, insulin resistance (HOMA index), adipocyte hypertrophy and a rise in basal superoxide anion (O2•⁻) production in gastrocnemius muscle and a downregulation of epididymal uncoupled protein-1 (UCP-1) protein staining. Treatment with LA prevented the development of hypertension, the rise in whole body weight and O2•⁻ production in gastrocnemius muscle, but failed to affect insulin resistance, hyperglycemia and hyperinsulinemia in ZDF rats. LA treatment resulted in a noticeable increase of pancreatic weight and a further adipocyte hypertrophy, along with a decrease in epididymal fat weight per body weight ratio associated with an upregulation of epididymal UCP-1 protein staining in ZDF rats. These findings suggest that LA was efficacious in preventing the development of hypertension, which could be related to its antioxidant properties. The anti-visceral obesity effect of LA appears to be mediated by its antioxidant properties and the induction of UCP-1 protein at the adipose tissue level in ZDF rats. Disorders of glucose metabolism appear, however, to be mediated by other unrelated mechanisms in this model of metabolic syndrome.
... In humans, it is synthesized from octanoic acid in the mitochondria (Jordan & Cronan, 1997). LA functions as an important cofactor for several important enzymes like pyruvate and a-ketoglutarate dehydrogenase complexes; it acts as a cofactor that bridges glycolysis and Kreb's cycle and it is able to cross the blood-brain barrier and acts as a redox couple with very low reduction potentials (Lodge et al., 1997). Due to these properties, LA is capable of regenerating other important antioxidants such as glutathione, vitamin C, and vitamin E (May et al., 1998). ...
... α-LA jest przyswajany z pożywienia głównie w postaci lipolizyny. Największą zawartość tego związku wykazano w szpinaku, brokułach, pomidorach i podrobach [9]. α-LA jest związkiem rozpuszczalnym zarówno w wodzie, jak i w tłuszczach, dzięki czemu może dotrzeć do większości tkanek organizmu [10]. ...
Article
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α-lipoic acid (α-LA) is a natural antioxidant found in food as a lipolysin. Both α-LA and its reduced form DHLA (dihydrolipoic acid) inhibit the production of reactive oxygen species (ROS) and reduce their harmful effects, as well as have the ability to chelate transition metal ions and regenerate other antioxidants. In addition to the antioxidant effect, they also have anti-inflammatory impact. Oxidative stress and inflammation play a key role in the pathogenesis of atherosclerosis and cardiovascular diseases. α-LA reduces the level of lipids in the blood, prevents oxidative modifications of the LDL molecule and inhibits the formation of atherosclerotic plaque. The nuclear factor κB (NF-κB) contributes to the development of atherosclerosis by activating proin-flammatory genes, and α-LA inhibits the inflammatory response induced by NF-κB by reducing oxidative stress, inhibiting the expression of adhesion molecules and the proliferation and migration of vascular smooth muscle cells. Also, α-LA supplementation can lower blood pressure. The paper reviews the researches on the role of α-LA in the pathogenesis of atherosclerosis and cardiovascular diseases.
... It has also been approved for use not only in pharmaceuticals but also as a food ingredient in Japan since 2004 and has been drawing attention as a dietary supplement in Japan [5]. ALA is a substance also called thioctic acid and is contained in the liver, heart, and kidneys of bovine or pigs [6]. It is also contained in vegetables such as spinach, tomatoes, and broccoli, but in very small amounts of approximately 1 mg/kg in animalderived food. ...
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In order to survey the research trends involving α-lipoic acid, which is a common dietary supplement, quantitative analysis of research titles related to α-lipoic acid listed in Google Scholar and PubMed was carried out by text mining. We gathered document titles containing α-lipoic acid from 26,370 and 5,496 articles from Google Scholar and PubMed, respectively, and constructed an analytical database for text mining. KH Coder (Windows version) was used to carry out the text mining analysis. We analyzed keyword transitions by time series for frequently occurring words obtained by morphological analysis. In addition, co-occurrence network analysis and cluster analysis were carried out, and analysis was conducted on the relationship between the research area and frequently occurring words. Between 1940 and 1959, there were many words related to basic research. Since the 2000s, words in the therapy area appeared most frequently. As a result of the co-occurrence network analysis, the word groups of "oxidative stress", "antioxidant activity", "diabetic neuropathy", and "diabetes patient" were formed around the base words of "rat" and "effect". On the other hand, a group consisting of "mitochondrial function", "pyruvate dehydrogenase", and "gene expression" was formed mainly around the base word "human". It was suggested that research on clinical applications was also carried out. In addition, as a result of hierarchical cluster analysis, the data were classified into six clusters, such as a cluster on basic research and clusters on clinical research; this clustering analysis showed the same tendency as the co-occurrence network. We classified each research area into six groups and determined the changes in research trends by year. As a result, we found that the basic research field has been decreasing year by year. In contrast, the clinical applied research field has been increasing. These results supported the results of co-occurrence network analysis, correspondence analysis, and hierarchical cluster analysis. Furthermore, as a result of keyword analysis related to enantiomers, the occurrences of the phrases "Optical" and "Enantiomeric" have been rapidly increasing since the 1980s. Co-occurrence network analysis was conducted on two categories, "Optical" and "Enantiomeric" which had many occurrences. Because of the analysis, groups related to "enantiomeric analysis", "enantiomeric synthesis", "pharmacology", and "pharmacokinetics" were formed and the studies on enantiomer of α-lipoic acid were considered to be centered in these areas. Especially, it was speculated that studies have mainly been conducted on the enantiomeric analysis of α-lipoic acid as a pharmaceutical. Furthermore, the phrase in another group of enantiomeric analysis suggested that studies of the bioavailability and pharmacokinetics of enantiomers have been conducted. Meanwhile, the word "drug" appeared in co-occurrence networks related to enantiomeric analysis, but phrases or words related to "dietary supplement" or "health foods" did not appear. Thus, it was considered that research on health foods related to enantiomers has not been conducted. These results suggest that the research relating to α-lipoic acid converges on the subjects related to basic research and clinical applications, and the clinical application domain has become the major research field for now. In addition, it is speculated that studies on enantiomeric analysis have increased, and studies on bioavailability and pharmacokinetics of enantiomers have also increased in particular.
... In animal tissues, LA is found in the kidney, the heart, and the liver. The most abundant plant sources of LA are spinach, followed by broccoli and tomatoes [69,76]. Moreover, several studies carried out in vivo, have shown that dietary supplementation with LA induced a decrease in oxidative stress, while restoring the diminished levels of the other antioxidants [71,77]. ...
Article
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Oxidative stress has been documented to be a key factor in the cause and progression of different retinal diseases. Oxidative cellular unbalance triggers a sequence of reactions which prompt cell degeneration and retinal dysfunction, both hallmarks of several retinal pathologies. There is no effective treatment, yet, for many retinal diseases. Antioxidant treatment have been pointed out to be an encouraging palliative treatment; the beneficial effects documented involve slowing the progression of the disease, a reduction of cell degeneration, and improvement of retinal functions. There is a vast information corpus on antioxidant candidates. In this review, we expose three of the main antioxidant treatments, selected for their promising results that has been reported to date. Recently, the sulforaphane, an isothiocyanate molecule, has been unveiled as a neuroprotective candidate, by its antioxidant properties. Progesterone, a neurosteroid has been proposed to be a solid and effective neuroprotective agent. Finally, the lipoic acid, an organosulfur compound, is a well-recognized antioxidant. All of them, have been tested and studied on different retinal disease models. In this review, we summarized the published results of these works, to offer a general view of the current antioxidant treatment advances, including the main effects and mechanisms described.
... Then, α-LA was converted to its S,S-diethoxycarbonyl methyl ester and quantified by GC with a flame photometric detector. Mild enzymatic hydrolysis of bovine, rat and rabbit tissues using protease released lipoyllysine, which could be determined photometrically by enzymatic NADH oxidation ( Akiba et al., 1998), which could also be determined by HPLC and electrochemical detection (Packer, 1997). ...
Article
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Lipoic acid plays vital role in energy metabolism. It is an excellent antioxidant acting inside the cell and at plasma membrane levels. It also acts as therapeutic agents in different diseases including diabetes, neurodegeneration, hypertension, HIV, breast cancer, heavy metal poisoning, radiation injury etc. Considering the nutritional and therapeutic perspectives, this is very important to identify α-lipoic acid-rich food. It is also required to determine whether concentration of α-lipoic acid gets changed with heat treatment. In this investigation, plant and animal foodstuffs were first blended with methanol, and then acidified, after that sonicated and finally centrifuged to extract α-lipoic acid. The concentrations of α-lipoic acid were estimated by the reverse phase high performance liquid chromatography (HPLC). Concentration of α-lipoic acid in the raw form of plant and animal foodstuffs ranged from 1.270671 ng/mg to 22.35785 ng/mg and 2.214241 ng/mg to 13.55982 ng/mg respectively. The level of α-lipoic acid in the boiled form of plant and animal foodstuffs ranged from 0.203982 ng/mg to 3.59858 ng/mg and 1.24481 ng/mg to 7.198254 ng/mg respectively. It was found that raw sample had higher concentration of α-lipoic acid than boiled sample. In our study, loss of α-lipoic acid due to boiling ranged from 10.85% to not detectable level for plant sample and 17.23% to 75.40% for animal sample indicating that α-lipoic acid in animal sample was more stable to boiling than that of plant sample. Further research should be continued to improve the stability of α-lipoic acid in different processed forms of foodstuffs.
... ALA (1,2-dithiolane-3-pentanoic acid) is a naturally occurring disulfide compound acting as a cofactor for several mitochondrial enzyme complexes that are involved in energy production. Animal-derived foods (red meat and liver, heart, and kidney) and plant sources (dark green leafy vegetables) [10,11] contain small amounts of ALA, detected in the form of lipoyllysine ranging from 0.55 to 2.36 µg/g dry mass in meats and from 0.16 to 3.15 µg/g dry mass in vegetables [12,13], from which ALA can be released by the combined action of gastric hydrolysis and lipoamidase. However, ALA cannot be detected in the blood of healthy subjects consuming these foods as part of a balanced diet [14]. ...
Article
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Endothelial dysfunction is recognized as an early sign of systemic atherosclerosis, and it represents a therapeutic target to prevent long-term cardiovascular (CV) consequences. Alpha-lipoic acid (ALA) is a commonly used dietary supplement exerting anti-oxidant and anti-inflammatory effects. We investigated whether a three-month treatment with ALA improves endothelial function, as assessed by flow-mediated dilation (FMD) of the brachial artery, and clinical and metabolic risk factors in overweight/obese youths. We enrolled 67 overweight/obese children, and 22 normal-weight metabolically healthy controls. Overweight/obese youths were randomly allocated in a double-blinded manner to receive ALA (n = 34) or placebo (n = 33). Of these, 64 (32 ALA, 32 placebo) completed the follow-up. At baseline, in ALA and placebo groups, FMD was similar, but lower as compared with that in controls (p = 0.045). At three months, within the ALA and placebo groups, FMD did not change significantly. However, the basal and peak diameter of brachial artery significantly increased after ALA treatment as compared to placebo (p = 0.036 and p = 0.01, respectively). There were no significant within- and between-group changes for anthropometric and metabolic variables. The results show that ALA supplementation improves vascular tone and may have a beneficial effect on CV health in overweight/obese youths.
... Alpha-lipoic acid (5-(1,2-dithiolan-3-yl)-pentanoic acid; ALA) can be found in low concentrations as natural antioxidant in plant sources such as spinach, broccoli and tomatoes (Lodge et al., 1997). Furthermore, ALA can be synthesized in the mitochondria in mammalian tissues such as testis, heart and liver which have high activity and great numbers of mitochondria (Carreau, 1979;Dupre et al., 1980;Morikawa et al., 2001). ...
Article
Randomized controlled trials (RCTs) have demonstrated that alpha lipoic acid (ALA) may change lipid profile, but their results are contradictory. The aim of this study is to conduct a meta-analysis to assess the effects of ALA on lipid profile. Electronic databases including ISI web of science, Ovid, PubMed/Medline, SCOPUS, and Google Scholar were searched up to February 2018. RCTs which assessed ALA effects on lipid profile were selected. Weighted mean difference (WMD) and 95% confidence intervals (CIs) in serum lipids concentrations were defined as intervention effects. Random effects model was used to estimate the pooled effect. Heterogeneity was measured by using I² test. The protocol was registered with PROSPERO (No. CRD42017072365). Database search retrieved 12 articles. Serum total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-) levels were significantly lower in subjects supplemented with alpha-lipoic acid compared with controls (WMD=−10.18 mg/dL; 95% CI: −16.16, −4.20 mg/dL; P = 0.001 and WMD=−9.22 mg/dL; 95% CI: −18.28, −0.16 mg/dL; P = 0.001, respectively), but no significant changes were found for high density lipoprotein-cholesterol (HDL-c) (WMD: 3.02 mg/dL; 95% CI: −0.39, 6.43; P = 0.082). The overall effect of ALA on serum triglyceride did not reveal any significant change, but in subgroup analysis based on health status (diabetic vs. non-diabetic), ALA decreased serum triglyceride levels in both diabetic and non-diabetic groups compared with controls. This meta-analysis revealed that ALA might favorably affect lipid profile especially LDL and TC. However, for confirming these results, more studies particularly among hyperlipidemic patients are needed.
... 4 LA is available in plant sources, such as spinach, broccoli and tomatoes, and in animal tissue including kidney, heart, and liver with the highest concentrations. 5 Nowadays, commercial LA is composed of Rand S-enantiomers with a 1:1 ratio, and has been used as therapeutic supplement in the treatment of several neurologic and metabolic diseases. 6 Recently, there has been considerable attention to the effectiveness of lipoic acid (LA) therapy in central nervous system (CNS) diseases. ...
Article
Objectives: α-lipoic acid (ALA) is a natural antioxidant which acts as a cofactor of bioenergetic mitochondrial enzymes. Along with its mitochondrial action, ALA and its reduced form have many biological functions resulting in a wide variety of actions such as anti-inflammation and antioxidant protection, scavenging reactive oxygen species, regenerating other antioxidant agents, such as vitamins C and E, and cytosolic glutathione, chelating the transitional metal ions (e.g. iron and copper), and modulating the signal transduction of nuclear factor. Methods: By selecting papers from PubMed, Science Direct, EBSCO, and databases, this review discusses the biochemical properties of LA, its mechanism of action, pharmacokinetics, and its possible therapeutic role in central nervous system diseases, such as Alzheimer’s disease, Parkinson’s disease, Multiple sclerosis, stroke, and spinal cord injury. Results: ALA as an antioxidant and anti-inflammation agent has therapeutical effects on central nervous system diseases, especially multiple sclerosis and PD. Discussion: ALA can be considered as a potentially useful treatment in central nervous disorders.
... Furthermore, DL-α-tocopherol (α-toco), a wellknown antioxidant and biologically active form of vitamin E, 33) (±)-α-lipoic acid (ALA), an antioxidant found in many foods, 34) and DL-sulforaphane (SFN), an indirect antioxidant derived from broccoli sprouts 35) were used for detection of their redox modulating effect. SFN has been reported to be an inducer of phase II antioxidant genes via the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. ...
Article
Mitochondrial impairment and the resulting generation of reactive oxygen species (ROS) have been associated with aging and its related pathological conditions. Recently, dietary antioxidants have gained significant attention as potential preventive and therapeutic agents against ROS-generated aging and pathological conditions. We previously demonstrated that food-derived antioxidants prevented intracellular oxidative stress under proteasome inhibition conditions, which was attributed to mitochondrial dysfunction and ROS generation, followed by cell death. Here, we further screened dietary antioxidants for their activity as redox modulators by visualization of the redox state using Redoxfluor, a fluorescent protein redox probe. Direct alleviation of ROS by antioxidants, but not induction of antioxidative enzymes, prevented mitochondria-mediated intracellular oxidation. The effective antioxidants scavenged mitochondrial ROS and suppressed cell death. Our study indicates that redox visualization under mitochondria-mediated oxidative stress is useful for screening potential antioxidants to counteract mitochondrial dysfunction, which has been implicated in aging and the pathogenesis of aging-related diseases.Direct alleviation of mitochondrial impairment-producing ROS by dietary antioxidants maintained intracellular redox state and improved cell viability.
... Kwas al fa -li po no wy znaj du je się w wy so kich stę że niach w czer wo nym mię sie, wą tro bie, sercu i ner ce. Źró dła ro ślin ne LA to m.in.: szpi nak, bro ku ły, po mi do ry, bruk sel ka, ziem nia ki, zie lo ny gro szek i otrę by ry żo we [43]. Po daż LA z po karmem przy sto so wa niu zwy kłej zbi lan so wa nej die ty nie wy star cza dla po kry cia za po trze bo wania or ga ni zmu z za bu rze nia mi me ta bo licz ny mi. ...
Article
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Alpha-lipoic acid as a part of standard treatment of diabetic neuropathy is influenced by patients’ compliance regarding avoiding food meantime drug ingestion. Patient education focused on drug and food bioavailability conflict is crucial for treatment effectiveness.
... In humans, it is synthesized from octanoic acid in the mitochondria (Jordan & Cronan, 1997). LA functions as an important cofactor for several important enzymes like pyruvate and a-ketoglutarate dehydrogenase complexes; it acts as a cofactor that bridges glycolysis and Kreb's cycle and it is able to cross the blood-brain barrier and acts as a redox couple with very low reduction potentials (Lodge et al., 1997). Due to these properties, LA is capable of regenerating other important antioxidants such as glutathione, vitamin C, and vitamin E (May et al., 1998). ...
Article
Acrylamide (ACR) is a well-known neurotoxicant and carcinogenic agent which poses a greater risk for human and animal health. The present study evaluates the beneficial effects of α-lipoic acid (LA) on ACR-induced neuropathy. A total of 40 male rats were divided into four groups: a placebo group; LA-treated group, administered orally 1% (w/w) LA mixed with diet; ACR-treated group, given 0.05% (w/v) ACR dissolved in drinking water; and LA + ACR-treated group, given LA 1% 7 d before and along with ACR 0.05% for 21 d. After 28 d, blood samples were collected, the rats were decapitated, and the tissues were excised for the measurement of brain biomarkers, antioxidant status, and hematological analysis. Also, the gait score of rats was evaluated. ACR-exposed rats exhibited abnormal gait deficits with significant (p < 0.05) decline in acetylcholine esterase (AChE) and creatine kinase in serum and brain tissues, respectively. However, the lactate dehydrogenase activity was increased in serum by 123%, although it decreased in brain tissues by -74%. ACR significantly (p < 0.05) increased the malondialdehyde level by 273% with subsequent depletion of glutathione S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and reduced the glutathione (GSH) level in brain tissue. Interestingly, LA significantly (p < 0.05) improved brain enzymatic biomarkers, attenuated lipid peroxidation (LPO), and increased antioxidant activities compared with the ACR-treated group. These results suggested that LA may have a role in the management of ACR-induced oxidative stress in brain tissues through its antioxidant activity, attenuation of LPO, and improvement of brain biomarkers.
... Životinjska tkiva koja su bogata lipolizinom su bubrezi, srce i jetra, dok su jestive biljke koje sadrže lipolizin spanać i brokoli. Male količine lipolizina su izmerene u paradajzu, grašku i kelju [17]. ...
... The most abundant plant sources of R-LA are spinach, followed by broccoli and tomatoes, which contain 3.15 Ϯ 1.11, 0.94 Ϯ 0.25, and 0.56 Ϯ 0.23 g lipoyllysine/g dry wt, respectively. The highest concentration of lipoyllysine in animal tissues was found in kidney, heart, and liver containing 2.64 Ϯ 1.23, 1.51 Ϯ 0.75, and 0.86 Ϯ 0.33 g lipoyllysine/g dry wt, respectively (Lodge et al., 1997). ...
... Životinjska tkiva koja su bogata lipolizinom su bubrezi, srce i jetra, dok su jestive biljke koje sadrže lipolizin spanać i brokoli. Male količine lipolizina su izmerene u paradajzu, grašku i kelju [17]. ...
Article
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Heavy metals as pollutants in the working and living environment are a serious health and environmental problem because they are toxic, non-biodegradable, accumulate in living systems and have a long half-life in soil. Sources of lead contamination are combustion products in the chemical industry and metallurgy, industrial waste water, landfills, traffic etc. Lead enters the body via the food chain and drinking water. In the body lead is deposited in the liver, kidneys, brain and mineral tissues. Excretion of lead causes damage to the epithelial cells of certain organs. High level exposure to cadmium is usually the result of environmental pollution by human activities. Exposure to cadmium can lead to acute and chronic tissue damage of various organs, including liver and kidneys in humans and in animals. In this paper we analyzed the effects of lead and cadmium exposure, in working and living environment, on the model system of experimental animals, particularly the activity of certain liver enzymes, acid and alkaline DNase, and standard biochemical blood parameters. The study showed that lead and cadmium significantly affect the protein content, red blood cells, hemoglobin and hematocrit, and the activity of liver enzymes. This harmful effect of this toxic metal can be reduced by the supplements.
... Vegetable and animal tissues contain low amounts of R-(+)-LA detected in the form of lipoyllysine (attachment of LA to specific lysine residues) [20]. The most abundant vegetable sources of R-LA are spinach, broccoli, and tomatoes, which contain 3.2, 0.9, and 0.6 × 10 −3 g lipoyllysine/g dry weight, respectively. ...
Article
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Diabetes has emerged as a major threat to worldwide health. The exact mechanisms underlying the disease are unknown; however, there is growing evidence that the excess generation of reactive oxygen species (ROS) associated with hyperglycemia, causes oxidative stress in a variety of tissues. In this context, various natural compounds with pleiotropic actions like α-lipoic acid (LA) are of interest, especially in metabolic diseases such as diabetes. LA, either as a dietary supplement or a therapeutic agent, modulates redox potential because of its ability to match the redox status between different subcellular compartments as well as extracellularly. Both the oxidized (disulfide) and reduced (di-thiol: dihydro-lipoic acid, DHLA) forms of LA show antioxidant properties. LA exerts antioxidant effects in biological systems through ROS quenching but also via an action on transition metal chelation. Dietary supplementation with LA has been successfully employed in a variety of in vivo models of disease associated with an imbalance of redox status: diabetes and cardiovascular diseases. The complex and intimate association between increased oxidative stress and increased inflammation in related disorders such as diabetes, makes it difficult to establish the temporal sequence of the relationship.
... Body tissues with lots of mitochondria (like heart, liver, kidney, and skeletal muscle) are good spots for finding lipoic acid. Yeast has also been shown to contain this vital nutrient (Lodge et al. 1997; Akiba et al. 1998; Lee and Na 2010; Tian et al. 2012). Though available from these normal nutritional sources, it is not likely that appreciable amounts of LA have been consumed in the typical western diet. ...
Article
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Antitumor agents are used in therapy against many forms of human cancer. One of these is mitomycin-C (MMC). As with many agents, it can interact with biological molecules and can induce genetic hazards in non-tumor cells. One of the possible approaches to protect DNA from this damage is to supply antioxidants that can remove free radicals produced by antitumor agents. Lipoic acid (LA) is known as one of the most powerful antioxidants. The aim of this study was to investigate antigenotoxic effects of LA against MMC induced chromosomal aberrations (CA), sister chromatid exchanges (SCE) and micronucleus (MN) formation in human lymphocytes. Lymphocytes were treated with 0.2 μg MMC/heparinized mL for 48 h. Three different concentrations (0.5, 1, 2 μg/mL) of LA were used together with MMC in three different applications; 1 h pre-treatment, simultaneous treatment and 1 h post-treatment. A negative, a positive and a solvent control were also included. In all the cultures treated with MMC + LA, the frequency of abnormal cells and CA/cell significantly decreased compared to MMC. Statistically significant reduction was also observed in SCE/cell and MN frequencies in all treatments. These results demonstrated anticlastogenic and antimutagenic effects of LA against MMC induced genotoxicity. LA showed the most efficient effect during 1 h pretreatment. On the other hand, MMC + LA treatments induced significant reduction in mitotic index than that of MMC treatment alone. These results are encouraging that LA can be a possible chemopreventive agent in tumorigenesis in both cancer patients and in health care persons handling anti-cancer drugs.
Article
Alpha lipoic acid is the most efficient of all known antioxidants for its lipo and hydrosolubility which enable easy penetrability in cytoplasm making its protection of free reactive radicals, energetic metabolism, regulation of genetic expresion etc. It has wide application in prevention and in therapy of diabetic angiopathy, neuropathy, cardiovascular, cerebrovascular, neurodegenerative disease, lesion, (insufficiency) of liver, HIV, intoxication with hard metals, mycotoxins etc. An important proprety of lipoic acid is its possibility to prevent or remove lesions which are caused by application aminogycosides and haloperidol (ototoxicity, nephrotoxicity) according to its wide application. R isomer of lipoic acid is physiological substance presented in organism which synthesize in in liver enabling its its application in relatively high dose for a longer period of time.
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An organism’s ability to function properly depends not solely on its diet but also on the intake of nutrients and non-nutritive bioactive compounds that exert immunomodulatory effects. This principle applies both to healthy individuals and, in particular, to those with concomitant chronic conditions, such as type 2 diabetes. However, the current food industry and the widespread use of highly processed foods often lead to nutritional deficiencies. Numerous studies have confirmed the occurrence of immune system dysfunction in patients with type 2 diabetes. This article elucidates the impact of specific nutrients on the immune system function, which maintains homeostasis of the organism, with a particular emphasis on type 2 diabetes. The role of macronutrients, micronutrients, vitamins, and selected substances, such as omega-3 fatty acids, coenzyme Q10, and alpha-lipoic acid, was taken into consideration, which outlined the minimum range of tests that ought to be performed on patients in order to either directly or indirectly determine the severity of malnutrition in this group of patients.
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Alpha‐lipoic acid (ALA) is a disulphide compound with multifunctional antioxidant properties and is soluble in both water and lipid. Several recent studies evaluated efficacy of ALA in various diseases related to oxidative damage such as diabetes, multiple sclerosis and Alzheimer and concluded that ALA can reduce oxidative stress by quenching reactive oxygen and nitrogen species, restoring antioxidants such as glutathione, vitamins C and E, and/or improving activity of antioxidant enzymes. Varicocele, an enlargement of the veins in scrotum, is considered as the most common repairable cause of male infertility and is associated with high levels of oxidative stress. In this study, surgical varicocele was induced in 30 adult male Wistar rats with other 20 rats serving as sham‐operated and nonoperated control. Varicocele caused significant worsening of sperm parameters, DNA damage and lipid peroxidation 2 and 4 months after surgery. A 2‐month ALA administration after surgery was able to revert these effects. These results clearly showed that ALA can reduce the negative side effects of elevated testicular temperature and increased oxidative stress in varicocelised rats. This study warrants future clinical research to assess whether ALA is of help in the treatment of infertile men with varicocele.
Chapter
Vitamins are low-molecular-weight organic compounds, indispensable for life activity in trace amounts for essential metabolic reactions, where deficiency causes specific disease symptom and do not include other essential nutrients such as dietary minerals, essential fatty acids, or essential amino acids, nor does it encompass the large number of other nutrients that promote health and do not provide cellular structural material and energy. Animals derived vitamins from plants and microorganisms. Vitaminoids are compounds with “vitamin-like” activity. Vitamins fall into two main groups: fat-soluble (e.g., A, D, E) and water-soluble (e.g., B, C, P) vitamins. Nutraceuticals include a number of substances ranging from natural diets, herbal products, biofortified crops, genetically modified, and processed food products. Nutraceuticals beyond basic nutrition provide health benefit, modulate immunity, and/or prevent and cure specific diseases. Functional foods are whole, fortified, enriched, or enhanced foods that provide health benefits beyond the provision of essential nutrients and classified into several groups on the basis of food group, the diseases it prevents or alleviates, physiological effects, etc. Food additives are antioxidants, food preservatives, food coloring agents, flavoring agents, anti-infective agents, excipients, and other similar substances used in the processing or storage of foods or animal feed. Excipients have little or no therapeutic value, but contribute largely to the performance of the active pharmaceutical ingredient (API) and maintain the quality, efficacy, safety, etc., of the formulation and include solvents, diluting, suspending, and emulsifying agents as well as antioxidants, preservatives, pharmaceutical, coloring agents, flavoring agents, vehicles, excipients, ointment bases, etc. Proteins and peptides allow the development of antibodies and different fermentations, purification processes, and recombination technology produced potential protein drugs at acceptable cost which can be useful in various diseases through various routes like oral, transdermal, nasal, pulmonary, ocular, buccal, and rectal. Many protein pharmaceuticals are available for treating rheumatoid arthritis, coronary artery thrombosis, multiple sclerosis, and chronic lymphocytic leukemia. Papain, a plant enzyme, is very helpful for the prevention of atherosclerosis and diabetic heart disease. Natural anesthetics, e.g., cocaine, methyl salicylate, capsaicin, piperine, opium, etc., have been in use since antiquity. Cosmeceuticals are cosmetic-pharmaceutical hybrid products intended to improve the health and beauty of the skin by providing a specific result, ranging from acne-control and anti-wrinkle effects to sun protection.
Article
Background: Madhuca indica J. F. Gmel. (Sapotaceae) is widely used ethnobotanically as anti-diabetic, antipyretic, hepatoprotective, anti-inflammatory and analgesic. It was shown to possess potent anti-apoptotic property. The aim of the study: To evaluate the possible mechanism of action of isolated phytoconstituent from Madhuca indica Leaves methanolic extract (MI-ALC) on arsenic-induced cardiotoxicity in rats. Materials and methods: The 3,5,7,3',4'-Pentahydroxy flavone (QTN) was isolated and characterized by using HPTLC, (1)H NMR, and LC-MS from MI-ALC. QTN (5, 10 and 20mg/kg, p.o.) was administered in arsenic intoxicated rats (5mL/kg, p.o.) for 28days and evaluated for various behavioral, biochemical, molecular and ultra-histological changes. Results: Treatment with QTN (10 and 20mg/kg, p.o.) significantly inhibited (p<0.05) arsenic-induced electrocardiographic, hemodynamic and left ventricular function alterations. Elevated levels of cardiac markers (LDH, CK-MB, AST, ALT, and ALP), altered lipid metabolism (total cholesterol, triglyceride, LDL, HDL, and VLDL) was significantly restored (p<0.05) by QTN. It also significantly inhibited (p<0.05) altered cardiac oxido-nitrosative stress, Na-K-ATPase level and mitochondrial enzymes (I-IV) activity after arsenite administration. QTN significantly increased (p<0.05) myocardial Nrf-2, PPAR-γ and significantly decreased (p<0.05) myocardial c-fos and c-jun mRNA expressions. Flow cytometric analysis showed that treatment with QTN (10 and 20mg/kg) significantly inhibited (p<0.05) arsenite-induce ROS and apoptosis. It also reduced ultra-histological aberrations induced by sodium arsenite. Conclusion: Administration of 3,5,7,3',4'- Pentahydroxy flavone (i.e. Quercetin (QTN)) isolated from MI-ALC showed significant protection against arsenic-induced oxido-nitrosative stress and myocardial injury via modulation of Nrf2, PPAR-γ, and apoptosis.
Chapter
There is increasing evidence that thiols play a role in various biological processes. This arises from their ability to undergo redox reactions; thus, they can act as efficient electron donators or acceptors. α-Lipoic acid is a dithiol-containing compound that plays an essential role in mitochondrial dehydrogenase reactions, but it has recently gained considerable interest as an antioxidant. Further investigations have shown lipoate to be an effective redox modulator of cell signaling and gene transcription. The various effects of α-lipoic acid at a cellular level are discussed here, highlighting the remarkable therapeutic potential for lipoate in a variety of disorders where oxidative stress is a factor.
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Powders of α-lipoic acid (ALA)/cyclodextrin (CD) complexes containing 9-24% (w/w) ALA were prepared to improve the gastrointestinal absorption of ALA. ALA and the ALA/CD complexes, corresponding to 30 mg/kg of body weight of ALA in rats and 600 mg of ALA in humans, were orally administered under fasting conditions. In rats, the area under the ALA plasma concentration/time-course curve from 0 to 3 h (AUC 0-3 h) for the ALA/G2-β-CD® complex was larger than that for ALA alone. In humans, after administration of 3 ALA/CD complexes with γ-CD, G2-β-CD® and Isoeleat®P, the ALA plasma concentration value 0.5 h after administration of the ALA/G2-β-CD® complex was significantly higher (p < 0.05) than that for ALA alone, and the AUC 0-3 h value for the ALA/G2-β-CD® complex was 1.4 times larger than that for ALA alone, although the difference was not significant. We suggest that the water-soluble ALA/G2-β-CD® complex powder can enhance ALA absorption in rats and humans.
Chapter
Alpha-lipoic acid (ALA), either as a dietary supplement or a therapeutic agent, modulates redox potential because of its ability to equilibrate between different subcellular compartments as well as extracellularly. Both the oxidized (disulfide) and reduced (dithiol: dihydrolipoic acid, DHLA) forms of ALA show antioxidant properties. ALA administered in the diet accumulates in tissues, and a substantial part is converted to DHLA via a lipoamide dehydrogenase. Commercial ALA is usually a racemic mixture of the R- and S-form. Chemical studies have indicated that ALA scavenges hydroxyl radicals, hypochlorous acid, and singlet oxygen. ALA exerts antioxidant effects in biological systems through the possibility of ROS quenching but also via an action on transition metal chelation. ALA is an essential cofactor for four enzyme complexes located in mitochondria. It is essential for energy production. ALA has been shown to possess a number of beneficial effects both in prevention and treatment of diabetes in experimental conditions. ALA presents beneficial effects in the management of symptomatic diabetic neuropathy and has been used in this context in Germany for more than 30 years. In cardiovascular diseases, dietary supplementation with ALA has been successfully employed in a variety of in vivo models associated with an imbalance of redox status: ischemia-reperfusion, heart failure, and hypertension. More mechanistic and human in vivo studies are needed to determine whether optimizing the dietary intake of ALA can help to decrease vascular diseases. A more complete understanding of the biochemical events occurring at a cellular level to influence oxidative damage is required to guide future therapeutic advances. Futures studies are warranted to elucidate the therapeutic effects of ALA in aging and cardiovascular diseases. © Springer-Verlag Berlin Heidelberg 2014. All rights are reserved.
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α-Lipoic acid, also known as thioctic acid, 1,2-dithiolane-3-pentanoic acid, 1,2-dithiolane-3-valeric, or 6,8-thioctic acid, is a naturally occurring potent antioxidant. It is present as lipoyllysine in various natural sources. In the plant material studied, the lipoyllysine content was the highest in spinach (3.15 μg/g dry weight; 92.51 μg/mg protein). When expressed as weight per dry weight of lyophilized vegetables, the abundance of naturally existing lipoate in spinach is over three- and five-fold higher than that in broccoli and tomato, respectively. A lower concentration of lipoyllysine is also detected in garden pea, brussel sprouts, and rice bran. However, lipoyllysine concentration has been found to be below detection limits in acetone powders of banana, orange peel, soybean, and horseradish. Lipoic acid is also an integral component of the mammalian cell. It is present in trace amounts as lipoamide in at least five proteins, where it is covalently linked to a lysyl residue. Four of these proteins are found in α-keto acid dehydrogenase complexes: pyruvate dehydrogenase complex, branched chain keto acid dehydrogenase complex, and α-ketoglutarate dehydrogenase complex. Three lipoamide-containing proteins are present in the E2 enzyme, dihydrolipoyl acyltransferase, which is different in each of the complexes and specific for the substrate of the complex. One lipoyl residue is found in protein X, which is the same in each complex. The fifth lipoamide residue is present in the glycine cleavage system.
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Publisher Summary Naturally occurring lipoic acid is known to play a fundamental role in metabolism, serving as a cofactor in enzyme complexes, which function at strategic points in carbohydrate metabolism, citric-acid cycle, and amino-acid catabolism. In the last decade, experimental evidence has increased suggesting free lipoic acid to be a powerful antioxidant and redox regulator, and, as such, a potentially useful therapeutic tool. It is important that the distribution and content of lipoic acid in plants and animals be ascertained. Therefore, a method for measuring the naturally occurring protein-bound form of lipoic acid (lipoyllysine) has been developed, and this method has been used to measure the lipoyllysine content of various plant and animal tissues. In lipoate-containing enzymes (α-keto acid dehydrogenases), lipoic acid is bound covalently to a lysine residue. This is an important consideration for determination as the release of lipoic acid is crucial. Previous methods have tried to overcome this problem via hydrolysis with strong acid/base; however, a larger amount of lipoic acid is lost by such methods, and recoveries of only 50% have been reported, and no more than 70% have been found. To overcome this problem, proteolytic hydrolysis was introduced to liberate lipoic acid. This also has the advantage of liberating the actual protein-bound form (lipoyllysine). Lipoic acid from animal tissues has been determined previously, but with methods of detection such as refractive index, ultraviolet, and GC mass spectroscopy. The former methods are inadequate as tissue hydrolysates contain a large amount of contaminants, which absorb around 330 nm, and GC methods require prior derivatization. To overcome these problems, an electrochemical detection system was introduced.
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Lipoic acid was first isolated by Reed in 1951. As lipoamide, this acid is a cofactor in multienzyme complexes that catalyze the oxidative decarboxylation of a-keto acids such as a-ketoglutarate and pyruvate. The strong antioxidant activity of lipoic acid and its reduced form, dihydrolipoic acid have been noted. Lipoic acid readily undergoes conversion to the reduced form, dihydrolipoic acid in vivo on receiving two electrons with the assistance of NADH. Dihydrolipoic acid is characterized by two thiol groups that are significantly involved in its antioxidnat activity. The lipoic acid is characterized by a strained 1, 2-dithiolane ring chromophore. The antioxidant activity of lipoic and dihydrolipoic acids is assessed in this study based on the molecular considerations.
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