The role of phospholipase A(2) and cyclooxygenase in renal toxicity induced by microcystin-LR

We have shown previously that exposure to microcystin-LR (MCLR) causes rena l toxic effects in isolated perfused rat kidney. That study was extended fu rther to approach the perspective of pharmacological blockade of renal toxi c effects by MCLR through the use of experimental therapeutic agents. An is olated kidney perfusion system was utilized and samples of urine and perfus ate were collected at 10 min intervals to determine the levels of inulin, s odium, potassium and osmolality. Dexamethasone (20 mug ml(-1)) and indometh acin (10 mug ml(-1)) were administered in the beginning of the perfusion an d MCLR was employed in a dose of 1 mug ml(-1) after an internal control of 30 min to evaluate the perfusion pressure (PP), renal vascular resistance ( RVR), glomerular filtration rate (GFR) and urinary how (UF). Dexamethasone and indomethacin antagonized the toxic effects of MCLR on PP, RVR, CFR and UF. Histologic analysis of dexamethasone and indomethacin treated groups di d not show any vascular or interstitial alterations. MCLR potentially impai rs the renal function, probably causing vascular and glomerular lesions and , promoting renal alterations through direct or indirect actions. These dat a seem to indicate that the: renal alterations promoted by MCLR involves al so phospholipase A(2) and arachidonic acid-derived mediators. (C) 2000 Else vier Science Ltd. All rights reserved.