Prevention of cisplatin-induced nephrotoxicity by glucosides of ascorbic acid and alpha-tocopherol.
BACKGROUND
Cisplatin is one of the most widely used cytotoxic therapeutic agents for the treatment of cancer. This drug, at effective higher doses, causes many physiological adverse effects such as nephrotoxicity and genotoxicity. The toxicity of the drug has been attributed to the induction of oxidative free radicals.


METHODS
Following intraperitoneal administration of cisplatin and ascorbic acid monoglucoside (AsAG) or alpha-tocopherol monoglucoside (TMG), investigations were conducted on levels of serum urea and creatinine, peroxidation of lipids in renal tissues, renal antioxidants and histopathology of renal tissue.


RESULTS
Administration of cisplatin to mice induced a marked renal failure, characterized by significant increase in serum urea and creatinine levels in addition to severe alterations in renal tissue architecture. Cisplatin also induced oxidative stress as indicated by increased lipid peroxidation and decreased levels of reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase in renal tissues. Administration of AsAG or TMG markedly reduced the cisplatin-induced higher plasma creatinine and urea levels and counteracted the deleterious effects of cisplatin on oxidative stress markers and protected the tissues from the cisplatin-induced lipid peroxidation.


CONCLUSIONS
These results indicated that AsAG or TMG has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of AsAG or TMG in human application for protecting against drug-induced nephrotoxicity.
Maliakel
Dani Mathew
DM
Amala Cancer Research Centre, Trichur 680555, Kerala, India.
Kagiya
Tsutomu V
TV
Nair
Cherupally Krishnan Krishnan
CK
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002945:Cisplatin / Q000633:toxicity*; D003401:Creatine / Q000097:blood; D004347:Drug Interactions; D005960:Glucosides / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D024505:Tocopherols / Q000494:pharmacology; D014508:Urea / Q000097:blood
D000970:Antineoplastic Agents; D000975:Antioxidants; D005960:Glucosides; C460320:tocopherol monoglucoside; D014508:Urea; D003401:Creatine; D001205:Ascorbic Acid; D002945:Cisplatin; D024505:Tocopherols