Differential Pre‐ and Post‐Treatment Effects of Low‐Dose Antidyslipidemic Drugs on Gentamicin‐Induced Acute Nephrotoxicity in the Rat: A Histopathological and Biochemical Study

Aminoglycoside-induced acute nephrotoxicity is a worldwide concern, while no effective preventive therapy exists. This study examined pre- and post-treatment effects of low doses of antidyslipidemic drugs such as fenofibrate (30 mg/kg/day, p.o.) and rosuvastatin (2 mg/kg/day, p.o.) in gentamicin (100 mg/kg/day, i.p.)-induced experimental acute nephrotoxicity in rats. Gentamicin-evoked nephrotoxicity was assessed via biochemical, molecular, and renal histopathological studies. Compared with normal rats, gentamicin-treated rats presented marked renal functional abnormalities with significant increases in the serum creatinine and urea levels, while there were no significant changes in the lipid profile. Pre-treatment with low-dose fenofibrate, but not post-treatment, in gentamicin-administered rats resulted in significant renal functional improvements. On the other hand, pre-treatment with low-dose rosuvastatin partially reduced gentamicin-induced increase in serum creatinine levels, but its post-treatment did not afford renal functional improvements. Renal histopathological analyses using hematoxylin-eosin, periodic acid Schiff, and Masson's trichrome staining revealed discernible incidences of acute tubular necrosis in the gentamicin-administered rats, which was prominently prevented by pre-treatments with both drugs but not markedly by their post-treatments. The renal structural and functional abnormalities in the gentamicin-administered rats were associated with significant increases in serum uric acid concentration, and renal inflammation as assessed by elevation of TNF-α levels, which were significantly attenuated by both pre- and post-treatments. In conclusion, low-dose fenofibrate pre-treatment but not post-treatment considerably prevented gentamicin-induced acute tubular necrosis and renal functional abnormalities. Despite effective prevention of gentamicin-induced acute tubular necrosis, pre-treatment with low-dose rosuvastatin provided partial protection against renal functional abnormalities, while its post-treatment was markedly ineffective.