Sulphur-containing Antioxidants Research Articles

Lead acetate-induced hepatoxicity in Wistar rats: possible protective role of combination therapy.

Experimental studies have shown that sulphur-containing antioxidants have beneficial effects against the detrimental properties of Pb. In the present study, we investigated the therapeutic potential of combined administration of N-acetyl cysteine (NAC; 50 mg/kg p.o.) and selenium (Se; 0.5 mg/kg p.o.) against lead acetate intoxication (Pb; 0.2% in water ad libitum) in a male rat model for 12 wk. The exposure of rats to lead acetate produced significant (P < 0.05) alterations in cytochrome P450 (CYP) activity, microsomal lipid peroxidation, reduced glutathione, and proteins. In addition, significant elevation in liver markers transaminases, triglycerides, cholesterol, and bilirubin as well as a decline in albumin were also compared with the experimental control rats. Combined treatment of lead-exposed animals with NAC and Se showed marked improvement of the biochemical, molecular, and histopathological findings. These experimental results strongly indicate the protective effect of NAC alone with Se against toxic effects of lead on liver tissue.

Combined Effect of N-Acetyl Cysteine, Zinc, and Selenium Against Chronic Dimethylmercury-Induced Oxidative Stress: A Biochemical and Histopathological Approach

Mercury (Hg), widely used in industry, is a great environmental health problem for humans and animals. Despite several reports regarding Hg toxicity, there is scarcity of data on its toxic manifestations on Sprague Dawley rats under realistic exposure conditions. Experimental studies have shown that sulphur-containing antioxidants have beneficial effects against the detrimental properties of Hg. The present work was aimed to study the therapeutic potential of combined administration of N-acetyl cysteine (NAC; 2 mmol/kg ip), zinc (Zn; 2 mmol/kg po), and selenium (Se; 0.5 mg/kg po) against dimethylmercury (DMM; 1 mg/kg po)-intoxicated male rats for 12 weeks. Exposure to DMM caused significant alterations in cytochrome P450 (CYP) activity, microsomal lipid peroxidation, and proteins. Activities of transaminases (aspartate aminotransferase/alanine aminotransferase), alkaline phosphatase, and lactate dehydrogenase in serum, as well as activities of CYP enzymes aniline hydroxylase (AH), amidopyrine-N-demethylase (AND) in liver microsomes and activities of acid phosphatase, alkaline phosphatase, glucose-6-phophatase, and succinic dehydrogenase in the liver and kidney, were significantly altered after DMM administration. DMM exposure also induced severe hepato-renal alterations at the histopathological level. NAC, along with Zn and Se, dramatically reversed the alterations in all of the variables more toward control. The study results conclude that protective intervention of combined treatment of NAC, along with Zn and Se, is beneficial in attenuating DMM-induced systemic toxicity.

Dose-dependent protection on cisplatin-induced ototoxicity - an electrophysiological study on the effect of three antioxidants in the Sprague-Dawley rat animal model.

SummaryBackgroundSprague-Dawley rats were used as an acute cisplatin ototoxicity model to compare the chemo-protective efficacy of 2 sulphur-containing antioxidants (D-methionine, N-L-acetylcysteine) and 1 seleno-organic compound (ebselen). Each putative chemo-protective agent was tested at 3 different dosages in order to assess the influence of dose on auditory preservation.Material/MethodsA total of 40 Sprague-Dawley albino male rats were used in the study. Animals were divided into 10 groups, 3 groups of different doses for each protective agent and a cisplatin-treated control group. The animals were weight-matched before drug exposure to ensure similar weights in all groups. Auditory function was assessed with auditory brainstem responses and distortion product otoacoustic emissions at time zero and at 96 hours post-treatment.ResultsAt the post-treatment follow-up no significant threshold change at 8 kHz was found in the D-Met- and NAC-treated groups. All ebselen-treated animals presented significant threshold elevations. At 12 and 16 kHz, only the groups treated with 300, 450 mg/kg of D-Met and 475 mg/kg of NAC presented thresholds comparable to the pre-treatment ABR data. The ebselen-treated animals presented significant threshold shifts and showed the highest threshold elevations. The DPOAE data analysis showed that only the animals from the 350 mg/kg D-met group presented lack of statistical differences between the pre and post recordings.ConclusionsConsidering the outcome from the ABR and DPOAE analyses together, only the 350 mg/kg D-met group presented a complete auditory preservation against the 14 mg/kg cisplatin administered i.v. Data from ebselen pre-treated Sprague-Dawley albino male rats demonstrate that ebselen dosages up to 12 mg/kg given by i.p. administration lack auditory preservation in this species.

Murine models of premature ageing for the study of diet-induced immune changes: improvement of leucocyte functions in two strains of old prematurely ageing mice by dietary supplementation with sulphur-containing antioxidants

Several immune functions are markers of health, biological age and predictors of longevity. A chronic oxidative and inflammatory state is the main cause of ageing and the immune system is involved in the rate of ageing. Thus, several murine models of premature ageing have been proposed owing to their early immunosenescence and oxidative stress, such as ovariectomised rats and mice, obese rats and anxious mice. In the last model, the most extensively studied by us, mice showing anxiety have an aged immune function and redox status as well as a shorter longevity in comparison with animals without anxiety of the same chronological age, being denominated prematurely ageing mice. A confirmation of the above is that the administration of diets supplemented with antioxidants improves the redox status and immune functions and increases the longevity of prematurely ageing mice. Antioxidant precursors of glutathione such as thioproline or N-acetylcysteine, which have a relevant role in ageing, have been the most widely investigated in adult prematurely ageing mice in our laboratory. In the present work, we have studied the effects of the ingestion for 5 weeks of a diet supplemented with 0·1% (w/w) thioproline+N-acetylcysteine on several functions of leucocytes from chronological old (69-73 weeks of age) prematurely ageing mice of two strains (Swiss and BALB/c). The results show an improvement of the immune functions, with their values becoming closer to those in adult animals (24±2 weeks). Thus, an adequate nutrition with antioxidants, even in aged subjects, could be a good strategy to retard ageing.

Antioxidant effects of methionine, α-lipoic acid, N-acetylcysteine and homocysteine on lead-induced oxidative stress to erythrocytes in rats

Lead, widely used in industry, is a great environmental health problem. Many studies have examined its effects on the health of both humans and animals. Experimental studies have shown that sulphur-containing antioxidants have beneficial effects against the detrimental properties of lead. The present study was designed to investigate markers of oxidative stress (hemoglobin (Hb) in whole blood, malondialdehyde (MDA) in sera; superoxidase dismutase (SOD) and glutathione peroxidise (GSH-Px) in erythrocyte hemolysate and vitamins A and E in plasma) in rats given lead (2000 ppm) with or without sulphur-containing antioxidants ( l-methionine (Met) (100 mg/kg/day), N-acetylcysteine (NAC) (800 mg/kg/day), l-homocysteine (Hcy) (25 mg/kg/day), lipoic acid (LA) (50 mg/kg/day)) in their water for 5 weeks. In the lead group, Hb and plasma vitamin E levels were significantly lower whereas MDA levels were significantly higher compared to controls ( p<0.05). Hb levels in lead–methionine and lead–LA groups were significantly higher than the lead group ( p<0.01). MDA levels were reduced in all groups compared to the lead group ( p<0.01). There was a decrease below control values in erythrocyte SOD ( p<0.01) and GSH-Px ( p<0.05) levels in the lead–LA group. Plasma vitamin A levels were significantly high in lead-methionine group compared to lead group ( p<0.01). In conclusion, the data suggests that oxidative stress induced by lead is reduced by sulphur-containing compounds.

Mitochondrial oxidative stress plays a key role in aging and apoptosis.

Harman first suggested in 1972 that mitochondria might be the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions. Later in 1980 Miquel and coworkers proposed the mitochondrial theory of cell aging. Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen radicals that exceed the cellular antioxidant defences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported between the rate of mitochondrial production of hydroperoxide and the maximum life span of species. An important change in mitochondrial lipid composition is the age-related decrease found in cardiolipin content. The concurrent enhancement of lipid peroxidation and oxidative modification of proteins in mitochondria further increases mutations and oxidative damage to mitochondrial DNA (mtDNA) in the aging process. The respiratory enzymes containing the defective mtDNA-encoded protein subunits may increase the production of reactive oxygen species, which in turn would aggravate the oxidative damage to mitochondria. Moreover, superoxide radicals produced during mitochondrial respiration react with nitric oxide inside mitochondria to yield damaging peroxynitrite. Treatment with certain antioxidants, such as sulphur-containing antioxidants, vitamins C and E, or the Ginkgo biloba extract EGb 761, protects against the age-associated oxidative damage to mtDNA and the oxidation of mitochondrial glutathione. Moreover, the EGb 761 extract also prevents changes in mitochondrial morphology and function associated with aging of the brain and liver.

Late onset administration of oral antioxidants prevents age-related loss of motor co-ordination and brain mitochondrial DNA damage

We have studied the effect of aging on brain glutathione redox ratio, on brain mitochondrial DNA damage and on motor co-ordination in mice and the possible protective role of late onset administration of sulphur-containing antioxidants. Glutathione redox ratios change to a more oxidized state in whole brain with aging but the changes are much more pronounced when this ratio is measured in brain mitochondria. The levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine in mitochondrial DNA are much higher in the brain of old animals than in those of young ones. Late onset oral administration of sulphur-containing antioxidants partially prevents oxidation of mitochondrial glutathione and DNA. There is an inverse relationship between age-associated oxidative damage to mitochondrial DNA and motor co-ordination in old mice.

Luminecent properties of several sulphur-containing antioxidants

Luminecent properties of several sulphur-containing antioxidants

A novel application of sulphur-containing antioxidants for the stablisation of polyolefins

The in-service performance of polymers is greatly affected by processing. Mechanooxidation reactions are responsible for the early failure of processed polymers. During processing, the initial formation of macroalkyl and peroxyl radicals is followed by the formation of hydroperoxides which are chiefly responsible for further radical-generating and polymer degradative reactions. Therefore adequate stabilisation is essential for plastics products. Under normal processing conditions, most sulphur-containing antioxidants are partially converted to oxidation products at elevated temperatures. In most cases these reaction products are more effective antioxidants than the compound added initially. It is shown here that controlled oxidation processing of polymers in the presence of sulphur-containing compounds can provide a highly effective antioxidant system. This approach to processing can be used further to promote desirable polymer-antioxidant reactions.

Mechanisms of antioxidant action: The mechanochemical attachment of sulphur-containing antioxidants to an ethylene-propylene-diene terpolymer

Sulphur-containing antioxidants are shown to react with an ethylene-propylene-diene terpolymer in a mechanochemical process. At 10% concentration, high yields of adduct are formed in the case of thiols. A sulphide reacts to a lower level.