Protective effect of simvastatin against adriamycin-induced nepherotoxicity in rats; biochemical and histological study

ABSTRACT

The usefulness of adriamycin [ADR], a potent anti-tumor antibiotic, is limited by the development of life-threatening cardiomyopathy and nephropathy. The cellular changes leading to these toxicities are suggested to be mediated by increased free radicals and lipid peroxidation. The current study was aimed to investigate the protective role of simvastatin [SIM] on adriamycin-induced nephrotoxicity in rat using biochemical, and histological approaches. Twenty eight healthy male Swiss albino rats were used and divided into four groups CONT [control], ADR [adriamycin treated], SIM [simvastatin treated], and SIM+ADR [simvastatin plus adriamycin treated]. Blood samples were collected and used to determine the serum urea, creatinine, albumin, and total protein levels. Both kidneys were removed, one of them was prepared for histological examinations and the other was stored at -70 °C for subsequent measurement of malondialdehyde [MDA], glutathione [GSH] contents and phase II antioxidants enzymes activities. Glutathione [GSH] level, glutathione-s-transferase [GST] and DT-diphorase activities were decreased, while the lipid peroxidation was increased in kidney tissue. Administration of SIM [cumulative dose, 60mg/kg body wt] in 12 equal injections [PO], before and concurrent with ADR, more or less prevented these nephropathic changes, normalized kidney function, and eliminated ascitis. Treatment with SIM was also accompanied by an increase in kidney GSH level as well as DT-diphorase activities with a concomitant decrease in lipid peroxidation. Histological examination revealed extensive and marked tubular necrosis in the ADR-treated kidney. Administration of Simvastatin reversed kidney damage with a marked reduction in tubular damage induced by ADR. These data show that SIM can provide coma protection against ADR nephropathy. This protective effect of SIM may be related to the antioxidant status on the kidney