Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats.

Cadmium (Cd) is a neurotoxic metal, which induces oxidative stress and membrane disturbances in nerve system. The garlic compound diallyl tetrasulfide (DTS) has the cytoprotective and antioxidant activity against Cd induced toxicity. The present study was carried out to investigate the efficacy of DTS in protecting the Cd induced changes in the activity of acetylcholinesterase (AChE), membrane bound enzymes, lipid peroxidation (LPO) and antioxidant status in the brain of rats. In rats exposed to Cd (3mg/kg/day subcutaneously) for 3 weeks, a significant (P<0.05) increase in the levels of LPO and protein carbonyls along with significant (P<0.05) decrease in the levels of reduced glutathione (GSH) and total sulphydryl groups (TSH) and the activities of AChE, superoxide dismutase, catalase, glutathione peroxidase, gluthione-S-transeferase, membrane bound enzymes (ATPases: Na(+)K(+)-ATPase, Mg(2+)-ATPase and Ca(2+)-ATPase) were observed in brain tissue. Oral administration of DTS (40mg/kg/day) with Cd significantly (P<0.05) diminished the levels of LPO and protein carbonyls and significantly (P<0.05) increased the activities of ATPases, antioxidant enzymes, GSH and TSH in brain. These results indicate that DTS attenuate the LPO and alteration of antioxidant and membrane bound enzymes in Cd exposed rats, which suggest that DTS protects the brain function from toxic effects of Cd.

Cadmium induced mitochondrial injury and apoptosis in vero cells: protective effect of diallyl tetrasufide from garlic.

Oxidative stress and mitochondrial injury has been implicated in cadmium-induced apoptosis. In this study, we examined the protective effect of diallyl tetrasulfide from garlic on cadmium induced oxidative stress and apoptosis in vero cells. Exposure of vero cells to cadmium (10 microM) for 18 h showed the apoptotic events such as loss of cell viability, alterations in nuclear morphology and decreased mitochondrial membrane potential with significantly increased levels of reactive oxygen species (super oxide anion and hydrogen peroxide). Treatment of vero cells with cadmium (10 microM) and diallyl tetrasulfide (5-50 microg/ml) showed that diallyl tetrasulfide attenuated the cadmium-induced suppression of cell viability in a dose dependent manner and highly significant effect was observed at 40 microg/ml. The nuclei morphological analysis with 4',6-diamidino-2-phenylindole staining confirmed that diallyl tetrasulfide at 40 microg/ml prevented the Cd (10 microM) induced apoptosis. Flow cytometric analysis with 2',7'-dichlorofluorencein diacetate showed that the inhibitory effect of diallyl tetrasulfide (10-40 microg/ml) on reactive oxygen species generation parallel with its effect on cell viability. In addition, diallyl tetrasulfide (40 microg/ml) remarkably reduced the cadmium-induced accumulation of superoxide radical and hydrogen peroxide with in cells. Further, diallyl tetrasulfide significantly protected the cadmium-induced decrease in mitochondrial membrane potential, an indicator of mitochondrial function. Our study suggest that diallyl tetrasulfide affect the reactive oxygen species generation induced by cadmium, and possesses a novel protective effect on the cytolethality associated with mitochondrial injury, which contributes to the antiapoptotic effect of diallyl tetrasulfide against cadmium.

Diallyl tetrasulfide protects cadmium-induced alterations in lipids and plasma lipoproteins in rats.

Lipoprotein abnormalities disrupt the levels of serum and cellular lipid, which accounts for the genesis of cardiovascular diseases. Cadmium (Cd) exposure is associated with a number of distinct pathological changes including dyslipidemia. Garlic and its organosulfur compounds seem to hold promise in reducing the risk factors associated with cardiovascular disease. The present study was undertaken to assess the effect of diallyl tetrasulfide (DTS) from garlic on Cd-induced alterations in the levels of lipids and lipoproteins in Wistar rats. Subcutaneous administration of Cd (3 mg/[kg body weight d]) for 3 weeks showed a significant (P < .05) increase in total cholesterol, very low density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, free fatty acids, and phospholipids, with a significant (P < .05) reduction in high-density lipoprotein cholesterol in plasma. In addition, the activity of hydroxy-3-methylglutaryl-coenzyme A reductase and the levels of cholesterol, free fatty acids, and triglycerides were significantly (P < .05) increased and the level of phospholipids was significantly decreased (P < .05) in liver of Cd-treated rats. Oral administration ofDTS (40 mg/[kg body weight d]) significantly (P < .05) reduced the levels of cholesterol, free fatty acids, triglycerides, very low density lipoprotein cholesterol, and low-density lipoprotein cholesterol; but the activity of hepatic hydroxy-3-methylglutaryl-coenzyme A reductase and the levels of high-density lipoprotein cholesterol increased (P < .05) in Cd-treated rats. Our results indicate that the administration of DTS afforded remarkable protection against Cd-induced alterations in lipid metabolism and thereby reduced the Cd-mediated cardiovascular diseases.

Role of diallyl tetrasulfide in ameliorating the cadmium induced biochemical changes in rats.

Cadmium (Cd) is an ubiquitous environmental and occupational toxic metal concerned with a variety of adverse effects. The present study was undertaken to evaluate the role of diallyl tetrasulfide (DTS), an organosulfur compound in alleviating the Cd induced biochemical changes in male Wistar rats. During the experiment, rats were injected with Cd (3mg/(kgday)) subcutaneously alone or with oral administration of DTS at different doses (10, 20 and 40mg/(kgday)) for 3 weeks. In Cd treated rats, the activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT) were significantly increased in serum with elevated levels of bilirubin, urea and creatinine. The hemoglobin level and creatinine clearance were also significantly decreased in Cd treated rats. In addition, the levels of plasma lipid peroxidation markers: thiobarbituric acid reactive substances and lipid hydroperoxides were significantly increased while the levels of plasma reduced glutathione (GSH), Vitamins C and E were significantly decreased in Cd administered rats. Administration of DTS along with Cd significantly decreased the serum, liver and kidney markers towards near normal level in a dose dependent manner. DTS at a dose of 40mg/(kgday) was highly effective when compared to other doses (10 and 20mg/(kgday)). DTS also significantly reduced the accumulation of Cd in blood and tissues as well as decreased the level of lipid peroxidation markers with elevation of antioxidants in plasma. All these changes were accompanied by histological observations in liver. The obtained results demonstrated the beneficial effect of DTS in reducing the harmful effects of Cd.