The Nephrotoxic Impact of Oseltamivir in Male Albino Rats after Repeated Exposure

Abstract

The effects of oseltamivir administration, effectively against influenza viruses A and B, on some selected parameters of rat kidney function were investigated to evaluate its possible nephrotoxic effects. Eighteen (18) albino male Wistar rats with body weights ranging from 150 - 190 g were divided into three groups, the first group (T1) was treated orally with 1 mg/kg BW as a therapeutic dose of oseltamivir for 7 consecutive days. The second group (T2) was treated with the same dose for six weeks, while the control group was dosed with distilled water. The results revealed a significant increase (P < 0.05) in blood urea nitrogen (BUN), serum uric acid and serum creatinine in group T2, while the T1 group showed a significant increase (P < 0.05) in serum uric acid only. Kidney histopathological lesions in the T1 rats showed atrophy of the glomerular tufts, dilation of the Bowman’s space, deposition of hyaline droplets within the lumen of the proximal and distal convoluted renal tubules, a cloudy swelling of the epithelial cells lining the renal tubules with perivascular lymphocytic cuffing and severe congestion of the interstitial renal blood vessels. The kidneys of the T2 rats showed necrosis of the epithelial cells lining the renal tubules and cystic dilation with complete dissolution of their epithelial linings. There was vacuolation of the glomerular tuft with proliferation of the parietal layer of the Bowman’s capsule, and a serum protein presence in the glomerular space. Mild interstitial fibrosis and thickening of the Bowman’s capsule were also observed. Similarly, there was fibrous thickening of the kidney capsule with mild medullary interstitial fibrosis. In conclusion, oseltamivir administered in repeated doses to rats induced some deleterious nephrotoxic effects in a time-dependent manner.