Ferric nitrilotriacetate (Fe-NTA) induces tissue necrosis as a result of lipid peroxidation (LPO) and oxidative damage that leads to high incidence of renal carcinomas. The present study was undertaken to evaluate the effect of diallyl sulphide (DAS) against Fe-NTA-induced nephrotoxicity. A total of 30 healthy male rats were randomly divided into 5 groups of 6 rats each: (1) control, (2) DAS (200 mg kg(-1)), (3) Fe-NTA (9 g Fe kg(-1)), (4) DAS (100 mg kg(-1)) + Fe-NTA (9 mg Fe kg(-1)) and (5) DAS (200 mg kg(-1)) + Fe-NTA (9 mg Fe kg(-1)). Fe-NTA + DAS-treated groups were given DAS for a period of 1 week before Fe-NTA administration. The intraperitoneal administration of Fe-NTA enhanced blood urea nitrogen and creatinine levels with reduction in levels of antioxidant enzymes. However, significant restoration of depleted renal glutathione and its dependent enzymes (glutathione reductase and glutathione-S-transferase) was observed in DAS pretreated groups. DAS also attenuated Fe-NTA-induced increase in LPO, hydrogen peroxide generation and protein carbonyl formation (p < 0.05). The results indicate that DAS may be beneficial in ameliorating the Fe-NTA-induced renal oxidative damage in rats.
Garlic contains diallylsulfide (DAS) and other structurally related compounds that are widely believed to be active agents in preventing cancer. This study shows the effect of DAS (a phenolic antioxidant used in foods, cosmetics, and pharmaceutical products) on ferric nitrilotriacetate (Fe-NTA)-induced hepatotoxicity in rats. Male albino rats of Wistar strain weighing 125-150 g were given a single dose of Fe-NTA (9 mg kg(-1) body weight, intraperitoneally) after 1 week of treatment with 100 and 200 mg kg(-1) DAS in corn oil respectively administered through the gavage. Fe-NTA administration led to 2.5-fold increase in the values of both alanine transaminase and aspartate aminotransferase, respectively, and 3.2-fold increase in the activity of lactate dehydrogenase, microsomal lipid peroxidation to approximately 2.0-fold compared to saline-treated control. The activities of glutathione (GSH) and other antioxidant enzymes decreased to a range of 2.2-2.5-fold. These changes were reversed significantly (p < 0.001) in animals receiving a pretreatment of DAS. DAS protected against hepatic lipid peroxidation, hydrogen peroxide generation, preserved GSH levels, and GSH metabolizing enzymes to 60-80% as compared to Fe-NTA alone-treated group. Present data suggest that DAS can ameliorate the toxic effects of Fe-NTA and suppress oxidant-induced tissue injury and hepatotoxicity in rats.
Strategies based on mesenchymal stem cell (MSC) therapy for restoring injured articular cartilage are not effective enough in osteoarthritis (OA). Due to the enhanced inflammation and oxidative stress in OA microenvironment, differentiation of MSCs into chondrocytes would be impaired. This study aims to explore the effects of diallyl disulfide (DADS) on IL-1β-mediated inflammation and oxidative stress in human adipose derived mesenchymal stem cells (hADSCs) during chondrogenesis. MTT assay was employed to examine the effects of various concentrations of DADS on the viability of hADSCs at different time scales to obtain non-cytotoxic concentration range of DADS. The effects of DADS on IL-1β-induced intracellular ROS generation and lipid peroxidation were evaluated in hADSCs. Western blotting was used to analyze the protein expression levels of IκBα (np), IκBα (p), NF-κB (np) and NF-κB (p). Furthermore, the gene expression levels of antioxidant enzymes in hADSCs and chondrogenic markers at days 7, 14 and 21 of differentiation were measured using qRT-PCR. The results showed that addition of DADS significantly enhanced the mRNA expression levels of antioxidant enzymes as well as reduced ROS elevation, lipid peroxidation, IκBα activation and NF-κB nuclear translocation in hADSCs treated with IL-1β. In addition, DADS could significantly increase the expression levels of IL-1β-induced impaired chondrogenic marker genes in differentiated hADSCs. Treatment with DADS may provide an effective approach to prevent the pro-inflammatory cytokines and oxidative stress as catabolic causes of chondrocyte cell death and enhance the protective anabolic effects by promoting chondrogenesis associated gene expressions in hADSCs exposed to OA condition.