Effects of microcystin-LR in isolated perfused rat kidney

Abstract

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 µg/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. Correspondence

Influence of Microcystin-LR on the activity of membrane enzymes in rat intestinal mucosa

“…Studies on electrolyte levels in serum showed a decrease in the content of sodium, potassium, calcium and phosphorus, which could be due to a reduction of the renal absorption induced by the toxin, as previously observed by NOBRE et al in isolated perfused rat kidney (20).…”

“…This microcystin is a potent hepatotoxin that accumulates in the liver, disrupting sinusoidal endothelial cells and causing hemorrhagic shock and rapid death in mice (17), rats (19), and fish (15). In addition, previous studies have showed that exposure to MCLR may cause renal toxic effects, including histopathological changes and modifications in the kidney functional parameters in rats (20) and fish (15). However, renal damage rarely occurs in mice.…”

Mitochondria a key role in microcystin‐LR kidney intoxication

“…Some conspicuous effects of microcystin-LR were also been reported on carp kidney (Rabergh et al, 1991). Many other studies show the nephrotoxicity promoted by microcystin-LR (Kotak et al, 1996;Nobre et al, 1999;Milutinovic et al, 2002Milutinovic et al, , 2003. Human intoxications were described for populations exposed through drinking water or recreational activities (Falconer, 1999) and for many patients submitted to renal dialysis treatment (Pouria et al, 1998;Azevedo et al, 2002;Soares et al, 2006).…”

“…Several studies have reported that microcystins induce severe hepatic hemorrhage leading to shock (Runnegar and Falconer, 1982) but also can affect rat kidney, indicating microcystin to be a potential nephrotoxic (Eriksson et al, 1988(Eriksson et al, , 1989Hooser et al, 1989;Nobre et al, 1999;Milutinovic et al, 2003). Some conspicuous effects of microcystin-LR were also been reported on carp kidney (Rabergh et al, 1991).…”

“…Furthermore, they release mediators capable of promoting nephotoxicity in isolated perfused rat kidney (Nobre et al, 1999), involving phospholipase A 2 and a cyclooxygenase in this process (Nobre et al, 2003). Many authors have already shown that MC-LR promotes renal alterations and affects renal physiology (Wickstrom et al, 1995;Nobre et al, 1998;Beasley et al, 2000;Fischer and Dietrich, 2000;Milutinovic et al, 2002).…”