Effects of microcystin-LR in isolated perfused rat kidney

Microcystin is a hepatotoxic peptide which inhibits protein phosphatase typ es 1 and 2A. The objective of the present study was to evaluate the physiop athologic effects of microcystin-LR in isolated perfused rat kidney, Adult Wistar rats (N = 5) of both sexes (240-280 g) were utilized. Microcystin-LR (1 mu g/ml) was perfused over a period of 120 min, during which samples of urine and perfusate were collected at IO-min intervals to determine the le vels of inulin, sodium, potassium and osmolality, We observed a significant increase in urinary flow with a peak effect at 90 min (control (C)= 0.20 /- 0.01 and treated (T) = 0.32 +/- 0.01 mi g(-1) min(-1), P<0.05). At 90 mi n there was a significant increase in perfusate pressure (C = 129.7 +/- 4.8 1 and T = 175.0 +/- 1.15 mmHg) and glomerular filtration rate (C = 0.66 +/- 0.07 and T = 1.10 +/- 0.04 mi g(-1) min(-1)) and there was a significant r eduction in fractional sodium tubular transport at 120 min (C = 78.6 +/- 0. 98 and T = 73.9 +/- 0.95%), Histopathologic analysis of the perfused kidney s showed protein material in the urinary space, suggestive of renal toxicit y. These data demonstrate renal vascular, glomerular and urinary effects of microcystin-LR, indicating that microcystin acts directly on the kidney by probable inhibition of protein phosphatases.