The present study brings out the preventive role of (-)-epigallocatechin-gallate (EGCG) on cardiac mitochondrial metabolism and apoptosis in cigarette smoke (CS)-exposed rats. The CS-exposed rats showed significantly decreased activities of TCA cycle enzymes and mitochondrial enzymatic antioxidants, on the other hand, mitochondrial lipid peroxidation was increased and GSH level was decreased. Further, CS exposure was found to induce cardiac apoptosis through release of cytochrome c into the cytosol, cleavage of pro-caspase-3 to active caspase-3, up-regulation of pro-apoptotic (Bax) and down-regulation of antiapoptotic (Bcl-2) molecules. The CS-induced apoptosis was further confirmed by mitochondrial and nuclear ultra structural apoptotic features as evaluated by electron microscopic studies. EGCG supplementation shelters the activities of TCA cycle enzymes and antioxidant enzymes, with concomitant decrease in lipid peroxidation and increase in GSH level. EGCG administration inhibited apoptosis through the inhibition of cytochrome c release into cytosol, activation of pro-caspase-3, down regulation of Bax and significant up regulation of Bcl-2. EGCG reversed the ultra structural apoptotic alterations of mitochondria and nucleus. The present study has provided experimental evidences that the EGCG treatment enduring to cardio protection at mitochondrial level.
Cyclosporine A (CsA) is the first choice immunosuppressant used for the prevention of allograft rejection in solid organ transplantation and immune-mediated diseases. Reactive oxygen species-induced oxidative stress and lipid peroxidation are implicated in the pathophysiology of CsA-induced renal injury. In this work, we have studied the effect of a garlic-derived compound, S-allylcysteine (SAC) on CsA-induced nephrotoxicity. CsA-induced nephrotoxicity was assessed in terms of increased activities of serum marker enzymes and levels of kidney markers. CsA administration induced significant elevation in lipid peroxidation along with abnormal levels of enzymic and non-enzymic antioxidants in the kidneys of the rats. SAC administration improved renal function by bringing about a significant decrease in peroxidative levels and increase in antioxidant status. Elevated expressions of inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-kappaB) due to CsA administration were reduced by SAC treatment. An increase in the expression of matrix metalloproteinase-2 (MMP-2) was evident in CsA-induced groups of rats, which was moderately reduced in SAC treated rats. An increase in the levels of serum constituent's urea, uric acid and creatinine was observed in the CsA-induced rats, which was reduced upon treatment with SAC. These results indicate that SAC has a protective action against CsA-induced nephrotoxicity which is also supported by histopathological studies. A comparative study of the antioxidant vitamin C and SAC is more valuable to assess the efficacy of the drug that can be used for the treatment of nephrotoxicity.
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