title: S-allylcysteine attenuates renal injury by altering the expressions of iNOS and matrix metallo proteinase-2 during cyclosporine-induced nephrotoxicity in Wistar rats.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy campus, Chennai-600 025, India.
authors.forename: Vinayagam
authors.initials: V
authors.lastname: Magendiramani
authors.forename: Syed
authors.initials: S
authors.lastname: Umesalma
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Kalayarasan
authors.forename: Ponnuraj
authors.initials: P
authors.lastname: Nagendraprabhu
authors.forename: Jagadeesan
authors.initials: J
authors.lastname: Arunkumar
authors.forename: Ganapasam
authors.initials: G
authors.lastname: Sudhandiran
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007166:Immunosuppressive Agents; C065299:S-allylcysteine; D016572:Cyclosporine; D052247:Nitric Oxide Synthase Type II; D020778:Matrix Metalloproteinase 2; D003545:Cysteine