THE EFFECTS OF FUMONISIN B-1 ON SEVERAL MARKERS OF NEPHROTOXICITY IN RATS

Rats were injected intraperitoneally with saline or fumonisin B-1 (FB1 ) at doses of 7.5 and 10.0 mg FB1/kg for 4 days, For each day of dosin g, 24-hr urine samples were collected and analyzed for creatinine and protein content and the enzymes gamma-glutamyltranspeptidase, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase, Twenty-four hours after the last dose, animals were killed and kidneys removed for ion t ransport measurement and histopathology. Significant increases in urin e volume and decreases in urine osmolality were observed in both FB1 d ose groups. Creatinine excretion was decreased only in the 10 mg FB1/k g group on the final day of the study. Urine protein excretion was ele vated in both treated groups and found to be due primarily to high-mol ecular-weight proteins indicative of increased glomerular permeability . Enzymuria, a marker of tubular cell damage, was also observed with i ncreases in the urinary excretion of all three enzymes measured, In re nal cortical slices tubular transport of the anion p-aminohippuric aci d was reduced by 75-80% and cationic transport of tetraethylammonium w as reduced by 40% in the FB1-treated animals, While these results sugg est significant alterations in renal function, only minor histopatholo gic changes were observed in the kidneys of both dose groups. Results of the present study indicate that urine volume, proteinuria, enzymuri a, and ion transport are sensitive indicators of early FB1-induced nep hrotoxicity. (C) 1995 Academic Press,Inc.