Oxidative and nitrosative stress mediated renal cellular damage induced by cyclosporine A: role of sulphated polysaccharides.
Oxidative and nitrosative stress are known to exert various adverse effects on biological systems and this seems to be one of the major contributor of nephrotoxicity induced by cyclosporine A (CsA), which is a major clinical challenge, despite its potent immunosuppressive effect. Sulphated polysaccharides of marine origin are well known for its antioxidant properties, among its other biological applications. CsA administration (25 mg/kg body weight, orally, for 21 d) showed increased level of oxidants and xanthine oxidase activity. CsA induced nitrosative stress was evident from a marked elevation in the expression of inducible nitric oxide synthase mRNA in renal tissue and a concomitant increase in plasma nitric oxide level. Augmented levels of malondialdehyde, 8-hydroxy-2-deoxyguanosine and protein carbonyl coupled with diminished protein thiols; hallmarks of lipid peroxidation, DNA damage and protein oxidation were noted in CsA administered rats. Membrane damage was further confirmed by altered ATPase activities in the renal tissue. Simultaneous treatment with sulphated polysaccharides (5 mg/kg body weight, subcutaneously) remarkably prevented the above alterations mediated by oxidative and/or nitrosative stress during CsA induction. Hence, these findings conclude that the use of an antioxidant agent like sulphated polysaccharides could be a useful tool in reducing CsA-induced nephrotoxicity.
Josephine
Anthony
A
Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India.
Amudha
Ganapathy
G
Veena
Coothan Kandaswamy
CK
Preetha
Sreenivasan P
SP
Varalakshmi
Palaninathan
P
D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D018384:Oxidative Stress; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism*
D007166:Immunosuppressive Agents; D011134:Polysaccharides; D026361:Reactive Nitrogen Species; D016572:Cyclosporine; D052247:Nitric Oxide Synthase Type II