NEPHROTOXICITY STUDY OF 7432-S IN RABBITS

Abstract

The nephrotoxic potential of 7432-S or its sodium salt (7432-S·Na) was studied in rabbits by giving the compounds orally by gavage or intravenously at a dose of 1000 mg/kg, respectively. A significant decrease in food consumption and a tendency to inhibit body weight gain were observed in all rabbits. The rabbits given 7432-S orally manifested a slight decrease in urinary pH and a slight increase in plasma creatinine and total cholesterol levels but no pathological changes in the kidney reflecting the nephrotoxicity of the compound. Slight or moderate proximal tubular necroses were observed in 3/4 rabbits given intravenous administration of 7432-S·Na. They also showed slight or moderate increase in protein, glucose and glanular cast in urinalysis and a tendency to increase in creatinine and urea nitrogen levels in plasma biochemical analysis. However, no significant difference was manifested in these parameters compared with the control. These results suggest that 7432-S has no nephrotoxic potential when orally administered, but 7432-S·Na manifests weak nephrotoxicity when administered intravenously at a dose of 1000 mg/kg.