Effects of microcystin-LR in isolated perfused rat kidney.
Microcystin is a hepatotoxic peptide which inhibits protein phosphatase types 1 and 2A. The objective of the present study was to evaluate the physiopathologic 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 microg/ml) was perfused over a period of 120 min, during which samples of urine and perfusate were collected at 10-min intervals to determine the levels 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 ml g-1 min-1, P<0.05). At 90 min there was a significant increase in perfusate pressure (C = 129.7 +/- 4.81 and T = 175.0 +/- 1.15 mmHg) and glomerular filtration rate (C = 0.66 +/- 0.07 and T = 1.10 +/- 0. 04 ml g-1 min-1) and there was a significant reduction in fractional sodium tubular transport at 120 min (C = 78.6 +/- 0.98 and T = 73.9 +/- 0.95%). Histopathologic analysis of the perfused kidneys showed protein material in the urinary space, suggestive of renal toxicity. 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.
Nobre
A C
AC
Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
Jorge
M C
MC
Menezes
D B
DB
Fonteles
M C
MC
Monteiro
H S
HS
D000818:Animals; D001427:Bacterial Toxins / Q000302:isolation & purification / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007674:Kidney Diseases / Q000378:metabolism; D008297:Male; D010456:Peptides, Cyclic / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic