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 bolus doses of 25, 50, 100 and 150 mg/kg menadione were used. For evaluation of cumulative toxicity, five doses of 100 and 150 mg/kg menadione were injected every other day. Histologic and ultrastructural examinations were made from tissues of kidney, heart, liver, lung, skeletal muscle of foreleg and smooth muscle of stomach. A dose-response relationship was observed in rats whether treated with single or five doses of menadione. Menadione at a dose of 25 mg/kg produced minimal granular degeneration 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, liver 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, granular degeneration in the cortex and necrosis. Apoptosis was very obvious in kidney from rats treated at 100 and 150 mg/kg menadione. Lesions found in the heart included inflammation, hemorrhage, vacuolization, edema and necrosis. Mitochondria were swollen. Hepatic changes included inflammation, degeneration, vacuolization and necrosis. The only lesion observed in lung was hemorrhage. At the same dose of menadione, structural damage was more severe in kidney than in other organs. The lesions produced by one dose of single injection of the drug were more severe than five doses of multiple injection of menadione in all observed tissues. We conclude that the acute toxicity of menadione is more severe than the cumulative toxicity of menadione.
Chiou
T J
TJ
Department of Medicine, Veterans General Hospital-Taipei, National Yang-Ming University, Taiwan, ROC.
Zhang
J
J
Ferrans
V J
VJ
Tzeng
W F
WF
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014812:Vitamin K / Q000633:toxicity*
D014812:Vitamin K; D005978:Glutathione; D002118:Calcium