CARDIAC AND RENAL TOXICITY OF MENADIONE IN RAT

Menadione induced oxidative stress in cells. The acute and cumulative toxic effects of menadione were evaluated by intravenous injection of the drug in Wistar rats. For evaluation of acute toxicity, single bolu s doses of 25, 50, 100 and 150 mg/kg menadione were used. For evaluati on of cumulative toxicity, five doses of 100 and 150 mg/kg menadione w ere injected every other day. Histologic and ultrastructural examinati ons were made from tissues of kidney, heart, liver, lung, skeletal mus cle of foreleg and smooth muscle of stomach. A dose-response relations hip was observed in rats whether treated with single or five doses of menadione. Menadione at a dose of 25 mg/kg produced minimal granular d egeneration in the tubular cells of the kidney. Menadione at a dose of 50 mg/kg produced minimal granular degeneration in the tubular cells of the kidney and mild pulmonary hemorrhage in the lung. Menadione at doses of 100 and 150 mg/kg produced lesions in the kidney, heart, live r and lung. The characteristic lesions in the kidney included tubular dilatation, formation of protein casts in the lumen of renal tubules, Ca2+ mineralization, vacuolization in proximal and distal tubules, gra nular degeneration in the cortex and necrosis. Apoptosis was very obvi ous in kidney from rats treated at 100 and 150 mg/kg menadione. Lesion s found in the heart included inflammation, hemorrhage, vacuolization, edema and necrosis. Mitochondria were swollen. Hepatic changes includ ed inflammation, degeneration, vacuolization and necrosis. The only le sion observed in lung was hemorrhage. At the same dose of menadione, s tructural damage was more severe in kidney than in other organs. The l esions produced by one dose of single injection of the drug were more severe than five doses of multiple injection of menadione in all obser ved tissues. We conclude that the acute toxicity of menadione is more severe than the cumulative toxicity of menadione. (C) 1997 Elsevier Sc ience Ireland Ltd.