Vitamin C attenuates cisplatin-induced alterations in renal brush border membrane enzymes and phosphate transport.
Cisplatin is a widely used antineoplastic agent that exhibits dose limiting nephrotoxicity. We have previously shown that the administration of cisplatin results in decrease in the activities of renal brush border membrane (BBM) enzymes and transport of inorganic phosphate (Pi) across BBM vesicles. In the present study we have investigated the effect of pre-treatment with vitamin C (ascorbic acid) on cisplatin-induced nephrotoxicity and changes in BBM enzymes and Pi transport. Administration of a single dose of cisplatin (6 mg/kg body weight) caused nephrotoxicity in rats that manifested biochemically as an elevation of serum urea nitrogen and creatinine levels. Treatment of rats with a single dose of vitamin C, six hours prior to administration of cisplatin, protected the kidney from the damaging effect of cisplatin. Vitamin C pre-treatment significantly decreased the urea nitrogen and creatinine levels. It attenuated the cisplatin-induced reduction in the activities of BBM and anti-oxidant enzymes and also Pi transport. These results suggest that vitamin C is an effective chemoprotectant against cisplatin-induced acute renal failure and dysfunction of the renal BBM in rats.
Fatima
Sabiha
S
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202002 UP, India.
Arivarasu
N A
NA
Mahmood
Riaz
R
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D001806:Blood Urea Nitrogen; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000970:Antineoplastic Agents; D000975:Antioxidants; D004798:Enzymes; D010710:Phosphates; D013438:Sulfhydryl Compounds; D003404:Creatinine; D002374:Catalase; D013482:Superoxide Dismutase; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D000520:alpha-Glucosidases; D007931:Leucyl Aminopeptidase; D001205:Ascorbic Acid; D002945:Cisplatin