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Antioxidant Effects of Sulfur-Containing Amino Acids
Abstract
Sulfur is an essential element for the entire biological kingdom because of its incorporation into amino acids, proteins and other biomolecules. Sulfur atoms are also important in the iron-containing flavoenzymes. Unlike humans, plants can use inorganic sulfur to synthesize sulfur-containing amino acids. Therefore, plants are an important source of sulfur for humans. Sulfur-containing compounds are found in all body cells and are indispensable for life. Some of sulfur-containing antioxidant compounds are, cysteine, methionine, taurine, glutathione, lipoic acid, mercaptopropionylglycine, N-acetylcysteine, and the three major organosulfur compounds of garlic oil, diallylsulfide, diallyldisulfide and diallyltrisulfide. In a comparison of the structure-function relationship among these sulfur-containing antioxidant compounds, dihydrolipoic acid (the reduced form of LA) is the most effective antioxidant. Dihydrolipoic acid contains two sulfhydryl groups and can undergo further oxidation reaction to form lipoic acid. The antioxidative activities of sulfur-containing compounds follow a general trend, the more highly reduced forms are stronger antioxidants and the number of sulfur atoms determine, at least in part, their modulatory activites on the glutathione related antioxidant enzymes. In this article, the antioxidant effects and the antioxidative activities, of sulfur-containing amino acids, are reviewed. In addition, the general antioxidant effects and the structure-function relationship of some sulfur-containing compounds are also reviewed.
... More so, ACE inhibits a potent vasodilator bradykinin (Tipnis et al., 2000). After discovered as a homologue of human ACE, the ACE2 acts as a carboxypeptidase, cleaves the basic amino acid in Cterminal residue, thereby hydrolyzing Ang-II to Ang (1)(2)(3)(4)(5)(6)(7) or produces Ang (1-9) (Simões e Silva et al., 2016; Shukla and Banerjee, 2021). Besides, ACE2, an important regulator of the RAS system, has been proven to have a very crucial role (by acting as a receptor mediating viral entry to the organism) in the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (Coto et al., 2021;Mascolo et al., 2021;Pagliaro et al., 2022). ...
... On the other hand, some organosulfur compounds such as diallyl sulfide, diallyl disulfide, N-acetyl cysteine, S-allyl cysteine, S-methyl cysteine (SMC), S-ethyl cysteine and Spropyl cysteine have reducing power, metal chelating ability, and superoxide ion scavenging activity (Hsu et al., 2004;Corzo-Martínez et al., 2007;Bayrak and Yanardag, 2021). Antioxidant effects of sulfur compounds have been studied by several researchers (Atmaca, 2004;Battin and Brumaghim, 2008). Sulfur-containing amino acids can be used to reduce cell damage induced by oxidative stress, because of their ROS removing ability (Moskovitz, 2005). ...
The angiotensin converting enzyme (ACE) catalyzes the conversion of angiotensin I to a key vasoconstrictor angiotensin II in renin-angiotensin system (RAS), thus playing an important role in both regulating blood pressure and maintaining fluid balance through RAS. Free radicals are continuously produced in the biological system. Therefore, organisms need both exogenous and endogenous antioxidants to guard against the damage caused by these free radicals. In this way, they prevent the occurrence of numerous diseases via protecting cellular components and biomolecules. The aim of the current study was to investigate the ACE inhibitory and antioxidant activities of sulfur compounds. The ACE inhibitory and antioxidant activities of all sulfur compounds increased in a concentration-dependent manner. Among these compounds, methionine had the highest ACE inhibitory and antioxidant activityes based on reducing power, DPPH radical scavenging and ORAC methods. Cystine had the highest ABTS radical scavenging, FRAP and nitrite scavenging activities. However, S-benzyl cysteine and S-phenyl cysteine exhibited the lowest ACE inhibitory and antioxidant activities, respectively. These outcomes indicate that sulfur compounds have both ACE inhibitory and antioxidant activities and may serve as gateways for research toward understanding the beneficial pharmacological effects of sulfur compounds against cell damage caused by oxidative stress.
... Considering that the content of cysteine and methionine sulfur-containing amino acids known to have antioxidant activity (Atmaca, 2004) increased significantly compared to that before digestion, the peptide extracts can be expected to have higher antioxidant activities after the digestion process. According to Hougland et al. (2013), histidine, tryptophan, and tyrosine are also representative reactive amino acids that can exhibit effective antioxidant activity by reacting with active oxygen species. ...
... Methionine can act as an endogenous antioxidant, and is an efficient remover of almost all oxidizing molecules under physiological conditions such as H 2 O 2 and hydroxyl radicals (Atmaca, 2004;Levine et al., 1996). The results of the present study also confirm that the consumption of beef-derived peptide extracts can have antioxidant effects on the body. ...
This study was conducted to compare and analyze the changes in the biochemical characteristics and biological activity of peptide extracts derived from Chickso, Hanwoo, and Wagyu beef during digestion. The results of the in vitro digestion analysis revealed that the digestion rate, total free amino acid content, and antioxidant and antihypertensive activities of Chickso loin and shank myofibrillar proteins were significantly higher (p<0.05) than those of Hanwoo and Wagyu loin and shank myofibrillar proteins. Particularly, the peptide extracts of Chickso loin and shank had a high angiotensin-converting enzyme inhibitory activity. In mice in vivo digestion experiment, the blood serum of mice fed with Chickso loin peptide extract (<10 kDa) showed the highest antioxidant enzyme activity. Thus, Chickso peptide extracts were deemed to be similar or more bioactive than Hanwoo and Wagyu peptide extracts, and can be used as bioactive materials.
... Cysteine (Cys) is considered a semi-essential amino acid since it can be converted from Met . Both Met and Cys are classified as sulfur amino acids (SAA) that possess potent antioxidant capacity due to their participation in glutathione synthesis (Bianchi et al., 2000;Atmaca, 2004;Bin et al., 2017). Several studies have also demonstrated that both SAA can directly scavenge reactive oxygen species (Elias et al., 2005;Moskovitz, 2005;Miura et al., 2014) further contributing to their antioxidant capabilities. ...
... However, in birds challenged with Eimeria, the induced oxidative stress and inflammation could potentially amplify the adverse consequences of Hcy accumulation, thereby further compromising bone health. Known that Cys also possesses potent antioxidant capacity without contributing to Hcy accumulation (Atmaca, 2004;Otasevic and Korac, 2016). Partially substituting Met supplementation with Cys in diets of broilers challenged by Eimeria might potentially improve the bone health of the birds. ...
Despite the acknowledged significance of nutrition in bone development, effects of methionine (Met) and cysteine (Cys) on bone quality remain under-researched, particularly during Eimeria challenge. We investigated the effects of different supplemental Met to Cys ratios (MCR) on bone quality of broilers under Eimeria challenge. A total of 720 fourteen-day old Cobb500 broilers were allocated into a 5 × 2 factorial arrangement. Five diets with Met and Cys supplemented at MCR of 100:0, 75:25, 50:50, 25:75, and 0:100 were fed to the birds with or without Eimeria challenge. Body composition was measured by dual energy x-ray absorptiometry, and the femur bone characteristics were assessed by microtomography. Data were analyzed by two-way ANOVA and orthogonal polynomial contrast. The results reaffirmed the detrimental effects of Eimeria challenge on bone quality. On 9 d post inoculation (DPI), significant interaction effects were found for whole body bone mineral content (BMC), lean tissue weight, and body weight (P < 0.05); in the nonchallenged group (NCG), these parameters linearly decreased as MCR decreased (P < 0.05). In the challenged group (CG), body weight and lean tissue weight were unaffected by MCR, and BMC linearly increased as MCR decreased (P < 0.05). For the cortical bone of femoral metaphysis on 6 DPI, bone mineral density (BMD) linearly increased as MCR decreased (P < 0.05). Bone volume to tissue volume ratio (BV/TV) in the CG linearly increased as MCR decreased (P < 0.05). On 9 DPI, BMC and TV linearly increased as MCR decreased (P < 0.05) in the NCG. BMD and BV/TV changed quadratically as MCR decreased (P < 0.05). For the trabecular bone of femoral metaphysis on 9 DPI, BV/TV, and trabecular number linearly increased as MCR decreased (P < 0.05) in the NCG. For the femoral diaphysis, BV, TV, BMC on 6 DPI, and BMD on 9 DPI linearly increased as MCR decreased (P < 0.05). In conclusion, this study showed that both Eimeria challenge and varying supplemental MCR could influence bone quality of broilers.
... Plasma thiols, which are of great importance in physiological and biological events, can exhibit pro-oxidant or predominantly antioxidant effects. [16,17] Antioxidants containing thiol (-SH) groups in their structures include pyridoxine, methionine, S-adenosylmethionine, N-acetylcysteine (NAC), alpha-lipoic acid, captopril, taurine, and homocysteine. Cysteine, homocysteine, and glutathione (GSH) are found in abundance among plasma thiols. ...
Objective: To investigate the potential relation between dynamic thiol homeostasis and blood transfusion in the pediatric intensive care unit. Methods: Blood samples were collected from pediatric intensive care patients before and after erythrocyte suspension transfusion and from donor blood additionally to measure thiol levels. The study involved 30 patients, including nine females, and a total of 90 blood samples from patients and donors were analyzed. Results: Prior to transfusion, Total Thiol (TT) and Native Thiol (NT) were 414.77 ± 156.14 (μmol/L) and 272.63 ± 115.75 (μmol/L), respectively, and post-transfusion, they were found to decrease to 398.07 ± 187.38 (μmol/L) and 258.97 ± 136.2 (μmol/L), respectively. However, no statistically significant difference was observed between pre- and post-transfusion values. In post-transfusion blood samples, there was a significant increase in Disulfide/TT and Disulfide/NT ratios, indicating an increase in oxidation (34.79 ± 92.34 and 51.89 ± 68.51, respectively), yet no statistical difference was noted. Conclusion: Transfusions administered in the Pediatric Intensive Care Unit were associated with a decrease in total and native thiol levels, indicative of increased oxidative stress, despite the lack of statistically significant differences. To mitigate the potential negative impact on patients with high oxidative properties after transfusions, strengthening the antioxidant defense system is recommended. Research should be planned to develop suitable strategies for enhancing the antioxidant defense system and ensuring patients' resilience to this condition.
... As previous studies showed, the detrimental effects caused by coccidiosis on bone development were attributed to the elevated oxidative stress and imbalance between osteoclast and osteoblast activities [19,20]. Extra dietary levels of Met could potentially alleviate the impacts of coccidia challenge on bone health due to its potent antioxidant capacity and immune modulatory effects [21][22][23][24]. The reduction in dietary crude protein (CP) content has been advocated for its numerous advantages, including cost reduction, decreased nitrogen excretion, and improved litter quality [2,[25][26][27][28][29]. ...
Simple Summary
Coccidiosis has been documented to adversely affect the bone quality of broilers. While the influence of minerals and vitamins on bone development has been studied, the impact of methionine supplementation on the bone health of broilers facing coccidia challenge remains inadequately explored. This study aimed to provide insights into the effects of varying dietary methionine levels in normal or reduced protein diets on the bone quality of broilers challenged with coccidia, utilizing X-ray scanning techniques. Interestingly, our results showed that increased methionine levels were associated with decreased whole body bone mineral content and density. In the femur bone, higher methionine levels were associated with decreased cortical bone quality, while they improved trabecular bone quality in birds fed reduced protein diets. Overall, this study sheds light on the complex interplay between dietary methionine levels, protein content, and coccidiosis challenge on broiler bone health, providing information to improve the bone health and welfare of birds under coccidia challenge through nutritional interventions.
Abstract
This study investigated the effects of dietary methionine (Met) levels on the bone quality of broilers challenged with coccidia. A total of 600 fourteen-day-old male Cobb500 broilers were gavaged with mixed Eimeria spp. and randomly allocated into 10 treatment groups by a 2 × 5 factorial arrangement. Birds received normal protein diets (NCP) or reduced-protein diets (LCP), containing 2.8, 4.4, 6.0, 7.6, and 9.2 g/kg of Met. Data were analyzed via two-way ANOVA and orthogonal polynomial contrast. At 9 days post-inoculation (DPI), whole body bone mineral density (BMD) and bone mineral content (BMC) linearly decreased as Met levels increased (p < 0.05). For the femoral metaphysis bone quality at 9 DPI, BMD linearly decreased, and porosity linearly increased as Met levels increased (p < 0.05) in the cortical bone. The increased Met levels linearly improved trabecular bone quality in LCP groups (p < 0.05) while not in NCP groups. For the femoral diaphysis cortical bone at 6 DPI, LCP groups had higher BMD and BMC than NCP groups (p < 0.05). Bone volume linearly increased as Met levels increased in LCP groups (p < 0.05) while not in NCP groups. In summary, the results suggested that increased Met levels decreased the cortical bone quality. However, in the context of reduced-protein diets, the increased Met levels improved trabecular bone quality.
... Both the number of sulfur atoms and the oxidation state of the sulfur atoms can influence overall antioxidant potential. 130 While allicin is effective in retarding the oxidation of methyl linoleate, it is less than that caused by α-tocopherol. 131 Organosulfur compounds such as SAC are recognized as powerful antioxidants and radical scavengers with a strong ability to minimize oxidation. ...
immunocompetenceImmunocompetence7 and possibly even mental function8 testify to its health, and the consequences can be extremely widespread. Garlic, a member of the Alliaceae family, is one of the more economically important cultivated crops. A large amount of garlic is produced annually in China and India. 5.65 million cwt. of garlic was harvested from 32,800 acres in the U.S. in 2002. About 80% of this amount is produced in California. Although significant consumption occurs as fresh garlic, it is also found as dehydration, flakes, and salts in various food preparations. There are also dozens of garlic supplements commercially available as essential oils, garlic-oil macerate, garlic powder, or garlic extract. Garlic continues to be one of the best-selling herbs in the US.
Cooking fumes and biomass smoke pose significant threats to air degradation and human health, especially to people who work in this field on a daily basis, due to the large amounts of hazardous pollutants released from grilling activities. Chronic exposure to these fumes is associated with a risk of inflammation and oxidative stress, which can increase the risk of atherosclerosis. In this study, the lipid profile Glutathion (GSH) and Malondialdehyde (MDA) of workers in fast food restaurants and patients with atherosclerosis were evaluated. The study included 40 Atherosclerosis patients, 40 fast food workers, and 40 healthy individuals as a control group, the ages ranges of (20-40) years. The obtained results indicated a significant increase in cholesterol, triglycerides, LDL, and VLDL and a decrease in HDL (p < 0.01) in patients and fast-food workers compared to control group. The results also indicated a significant increase in the level of MDA, and a significant decrease in the level of GSH for patients and fast-food workers compared to the control. In conclusion, it appears that fast food workers experience oxidative stress and disruption in lipid metabolism that may increase the risk of atherosclerosis. Therefore, safety and quality control measures must be strengthened to reduce the occupational risks of fast-food restaurant workers.
Nitryl chloride, formed by reaction of hypochlorous acid with nitrite, might contribute to nitrative damage of biomolecules in addition to peroxynitrite. Damage of DNA by these reactive nitrogen oxide species is implicated in carcinogenesis associated with chronic infections and inflammation. Nitrated DNA adducts, such as 8-nitroguanine and 8-nitroxanthine, are not stable in DNA since they undergo spontaneous depurination, leading to apurinic site formation. In this report, we investigate the protective effect of biological and dietary antioxidants in inhibiting DNA nitration induced by nitryl chloride. The effect of inhibition was evaluated by decrease of 8-nitroxanthine and 8-nitroguanine formation. Among the 21 compounds examined, dihydrolipoic acid, is the most effective in preventing DNA nitration, followed by N-acetyl-L-cysteine and folic acid. For sulfur-containing compounds, the more highly reduced compounds are stronger inhibitors of DNA nitration. The major product of N-acetyl-L-cysteine reaction with nitryl chloride is characterized as the (R)-2-acetylamino-3-sulfopropionic acid, a physiologically irreversible product, suggesting that nitryl chloride is a strong oxidizing agent.
Reaction rate constants between superoxide (O2−) and natural anti-oxidants, amino acids and some related sulfur-containing compounds were determined by quenching the chemiluminescence of a Cypridina luciferin analogue, 2-methyl-6-phenyl-3,7-dihydroimidazo[1,2-a]pyrazin-3-one (CLA) in pH 7.0 buffer solutions at 25°C as described in our previous report. The results are discussed in comparison with the literature data. We found that the present method can be applied to measured antioxidative activity of even a fairly unstable sample.
Lipid peroxidation is thought to be an important event contributing to the toxicity of a variety of compounds like perchloroethylene (PER). PER is known to produce membrane damage through increased lipid peroxidation. An investigation of the relative importance of vitamin E and taurine in rendering protection to liver and kidney against PER induced cellular damage was performed. PER administered (3000 mg/kg body weight/day) mice were subjected to vitamin E (400 mg/kg body weight/day) and taurine (100 mg/kg body weight/day) treatment respectively for 15 days to study their individual effect on lipid peroxidative changes. A defective antioxidant defense system in PER administered mice was evidenced by the low level of enzymic antioxidants (SOD, CAT, GPx) and non-enzymic antioxidants (glutathione, ascorbic acid, total thiols, non-protein thiols, and vitamin E), with a simultaneous increase in lipid peroxidation (LPO) level. Vitamin E and taurine supplemented mice showed a marked reversal of these metabolic changes related to cellular damage caused by PER. These results suggest that PER induced cellular damage may be associated with lipid peroxidation and that can be effectively prevented by both vitamin E and taurine.
Oxidative stress has a key role in the pathogenesis of diabetic complications. We have previously reported that taurine (T), which is known to counteract oxidative stress in tissues (lens, kidney, retina) of diabetic rats, attenuates nerve blood flow and conduction deficits in early experimental diabetic neuropathy (EDN). The purpose of this study was to evaluate whether dietary T supplementation counteracts oxidative stress and the nerve growth factor (NGF) deficit in the diabetic peripheral nerve. The experiments were performed in control rats and streptozotocin-diabetic rats fed standard or 1% T-supplemented diets for 6 weeks. All measurements were performed in the sciatic nerve. Malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HA) were quantified with N-methyl-2-phenylindole. GSH, GSSG, dehydroascorbate (DHAA), and ascorbate (AA) were assayed spectrofluorometrically, T by reverse-phase HPLC, and NGF by ELISA. MDA plus 4-HA concentration (mean ± SEM) was increased in diabetic rats (0.127 ± 0.006 vs 0.053 ± 0.003 μmol/g in controls, P < 0.01), and this increase was partially prevented by T (0.096 ± 0.004, P < 0.01 vs untreated diabetic group). GSH levels were similarly decreased in diabetic rats treated with or without taurine vs controls. GSSG levels were similar in control and diabetic rats but were lower in diabetic rats treated with T (P < 0.05 vs controls). AA levels were decreased in diabetic rats (0.133 ± 0.015 vs 0.219 ± 0.023 μmol/g in controls, P < 0.05), and this deficit was prevented by T. DHAA/AA ratio was increased in diabetic rats vs controls (P < 0.05), and this increase was prevented by T. T levels were decreased in diabetic rats (2.7 ± 0.16 vs 3.8 ± 0.1 μmol/g in controls, P < 0.05) and were repleted by T supplementation (4.2 ± 0.3). NGF levels were decreased in diabetic rats (2.35 ± 0.20 vs 3.57 ± 0.20 ng/g in controls, P < 0.01), and this decrease was attenuated by T treatment (3.16 ± 0.28, P < 0.05 vs diabetic group). In conclusion, T counteracts oxidative stress and the NGF deficit in early EDN. Antioxidant effects of T in peripheral nerve are, at least in part, mediated through the ascorbate system of antioxidative defense. The findings are consistent with the important role for oxidative stress in impaired neurotrophic support in EDN.
The effect of two naturally occurring thiols, such as cysteine and homocysteine, has been examined for their ability to induce deoxyribose degradation and DNA damage. Copper(II) ions have been added to incubation mixtures and oxygen consumption measurements have been performed in order to correlate the observed damaging effects with the rate of metal catalyzed thiol oxidation. Ascorbic acid plus copper has been used as a positive control of deoxyribose and DNA oxidation due to reactive oxygen species. Cysteine or homocysteine in the presence of copper ions induce the degradation of deoxyribose and the yield of 8-hydroxy-2′-deoxyguanosine (8-OHdG), although important differences are observed between the two thiols tested, homocysteine being less reactive than cysteine. DNA cleavage is induced by cysteine in the presence of copper(II) ions but not by homocysteine. Catalase and thiourea, but not superoxide dismutase (SOD), were shown to inhibit the damaging effects of cysteine on deoxyribose or DNA suggesting that H2O2 and OH radicals are responsible for the observed induced damage. The results indicate that there are differences between the damaging effects of the two thiols tested towards deoxyribose and DNA damage. The pathophysiological importance will be discussed.
Oxidative modification of human low-density lipoprotein (LDL) renders it atherogenic. Previous studies demonstrated that plasma thiols promote oxidation of LDL by free ferric iron (Fe3+). The current study investigated effects of plasma thiols on oxidation of LDL by hemin, a physiological Fe3+–protoporphyrin IX complex thought to be capable of initiating LDL oxidation in vivo. In contrast to free Fe3+ which is incapable of oxidizing LDL in the absence of an exogenous reductant, hemin readily promoted LDL oxidation. During incubation of LDL (0.2 mg of protein/ml) with hemin (10 μM) at 37°C for 6 h, thiobarbituric acid-reactive substances (TBARS), a marker of lipid oxidation, increased from 0.3 (±0.1) nmol/mg of LDL protein to a maximal concentration of 45.8 (±5.2) nmol/mg of LDL protein. Under the same experimental conditions, lipid-conjugated dienes, another marker of lipid oxidation, increased from non-detectable to near-maximal levels of 78–187 nmol/mg of LDL protein, and lipoprotein polyunsaturated fatty acyl-containing cholesteryl ester content decreased to 15–36% of that present in native (i.e. unoxidized) LDL. Continued incubation of LDL with hemin for up to 24 h resulted in no further significant alterations in lipoprotein levels of TBARS, lipid-conjugated dienes, and cholesteryl esters. In addition to these chemical modifications indicative of lipoprotein oxidation, agarose gel electrophoretic analysis indicated that exposure of LDL to hemin resulted in conversion of the lipoprotein to an atherogenic form as evidenced by its increased anodic electrophoretic mobility. Addition of physiological concentrations of plasma thiols (either cysteine, homocysteine or reduced glutathione; 1–100 μM, each) inhibited hemin-mediated oxidation of LDL. Thus, whereas the maximal TBARS concentration was achieved following 6 h of incubation of LDL with hemin alone, addition of thiol extended the time required to attain maximal TBARS concentration to ≥12 h. Similar antioxidant effects of thiols on formation of lipid-conjugated dienes, loss of cholesteryl esters, and lipoprotein anodic electrophoretic mobility were also observed. However, all thiols were not equally effective at inhibiting hemin-dependent LDL oxidation. Thus, whereas reduced glutathione was most effective at inhibiting hemin-dependent LDL oxidation, an intermediate effect was observed for homocysteine, and cysteine was least effective. The inhibition of hemin-mediated LDL oxidation by plasma thiols reported here confirms a previous observation that, under certain conditions, thiols can function as antioxidants, but contrasts with the previously documented pro-oxidant effect of the same thiols on oxidation of LDL by free Fe3+. These contrasting effects of plasma thiols on hemin- and free Fe3+-mediated LDL oxidation indicate that, in vivo, the ability of thiols to function as either anti- or pro-oxidants during LDL oxidation may, at least in part, be determined by the type of oxidant stress to which the lipoprotein is exposed.
Lipoic acid and its reduced derivative, dihydrolipoic acid (DHLA) are highly promising antioxidant agents, which are potent attenuators of reactive species-mediated damage in vitro and in animal studies. Lipoic acid is a universal antioxidant, effective in lipophilic and aqueous environments. In contrast to an equivalent endogenous agent, such as oxidised glutathione (GSSG), lipoic acid acts as an antioxidant in its oxidised form. Lipoic acid has been evaluated in diabetic polyneuropathy, a condition which is thought to result in part from oxidant damage caused by long-term hyperglycaemia. Diabetic patients are prone to incur enhanced cellular free radical formation and reduced antioxidant defence. Treatment with lipoic acid has improved nerve conduction velocity during studies in diabetic animals. Trials in diabetic patients have often observed some relief of neuropathic symptoms during treatment with lipoic acid, but consistent objective benefits have been difficult to establish. Lipoic acid is now used in Germany for the treatment of diabetic neuropathy and definitive evidence of efficacy should arise from postmarketing surveillance studies. It is possible that lipoic acid may be more effective as a long-term dietary supplement aimed at the prophylactic protection of diabetics from complications.
Lead (Pb) is known to negatively affect glutathione (GSH) metabolism in the lens. The present study examined the effects of Captopril, Taurine, and α-Lipoic acid on the Pb-induced GSH depletion and lipid peroxide increase in the lenticular system. Captopril administration returned the GSH, cysteine (CYS), and malondialdehyde (MDA) levels to near normal. Following Taurine administration the GSH, CYS and MDA levels were intermediate between the control group and the Pb group levels. α-Lipoic acid administration, however, only increased the CYS levels. No significant changes in oxidized glutathione (GSSG) levels were observed in any treatment group.
In vitro studies have shown that α-lipoic acid (LA) is an antioxidant. There is a paucity of studies on LA supplementation in humans. Therefore, the aim of this study was to assess the effect of oral supplementation with LA alone and in combination with α-tocopherol (AT) on measures of oxidative stress. A total of 31 healthy adults were supplemented for 2 months either with LA (600 mg/d, n = 16), or with AT (400 IU/d, n = 15) alone, and then with the combination of both for 2 additional months. At baseline, after 2 and 4 months of supplementation, urine for F2-isoprostanes, plasma for protein carbonyl measurement and low-density lipoprotein (LDL) oxidative susceptibility was collected. Plasma oxidizability was assessed after incubation with 100 mM 2,2′-azobis (2-amidinopropane) hydrochloride (AAPH) for 4 h at 37°C. LDL was subjected to copper- and AAPH-catalyzed oxidation at 37°C over 5 h and the lag time was computed. LA significantly increased the lag time of LDL lipid peroxide formation for both copper-catalyzed and AAPH-induced LDL oxidation (p < .05), decreased urinary F2-isoprostanes levels (p < .05), and plasma carbonyl levels after AAPH oxidation (p < .001). AT prolonged LDL lag time of lipid peroxide formation (p < .01) and conjugated dienes (p < .01) after copper-catalyzed LDL oxidation, decreased urinary F2-isoprostanes (p < .001), but had no effect on plasma carbonyls. The addition of LA to AT did not produce an additional significant improvement in the measures of oxidative stress. In conclusion, LA supplementation functions as an antioxidant, because it decreases plasma- and LDL-oxidation and urinary isoprostanes.
The effects of N-acetylcysteine (NAC), 2-mercaptopropionylglycine (MPG) and dithiothreitol (DTT) on the metabolism and toxicity of acetaminophen (APAP) were examined in isolated mouse hepatocytes maintained in primary culture on collagen-coated dishes. Both NAC and MPG increased the formation of the glutathione and sulfate conjugates of APAP and decreased the covalent binding of the APAP reactive metabolite to cellular protein. DTT did not increase APAP metabolism but did decrease covalent binding. NAC, MPG and DTT decreased plasma membrane damage, as measured by leakage of lactate dehydrogenase from hepatocytes, during a 4-h incubation in 5.0 mM APAP. NAC, MPG and DTT also reduced the APAP-induced fall in glutathione levels in these cells. In other experiments, hepatocytes were exposed to 5.0 mM APAP for 1 h and then incubated during a post-exposure period in APAP-free medium. Damage increased during this post-exposure incubation. Addition of DTT, but not NAC or MPG, after APAP exposure protected the hepatocytes from plasma membrane damage during the post-exposure period. These results indicate that NAC and MPG exert their protective effects by their action on the reactive metabolite of APAP. As well as its effect in reducing the formation of the reactive metabolite, DTT has a potent protective effect against the toxic processes initiated by the APAP reactive metabolite.