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 renal toxic effects in isolated perfused rat kidney. That study was extended further to approach the perspective of pharmacological blockade of renal toxic effects by MCLR through the use of experimental therapeutic agents. An isolated kidney perfusion system was utilized and samples of urine and perfusate were collected at 10min intervals to determine the levels of inulin, sodium, potassium and osmolality. Dexamethasone (20microg ml(-1)) and indomethacin (10microg ml(-1)) were administered in the beginning of the perfusion and MCLR was employed in a dose of 1microg ml(-1) after an internal control of 30min to evaluate the perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR) and urinary flow (UF). Dexamethasone and indomethacin antagonized the toxic effects of MCLR on PP, RVR, GFR and UF. Histologic analysis of dexamethasone and indomethacin treated groups did not show any vascular or interstitial alterations. MCLR potentially impairs the renal function, probably causing vascular and glomerular lesions and, promoting renal alterations through direct or indirect actions. These data seem to indicate that the renal alterations promoted by MCLR involves also phospholipase A(2) and arachidonic acid-derived mediators.
Nobre
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AC
Department of Physiology and Pharmacology, Federal University of Ceara, Rua Cel. Nunes de Melo, 1127, 60430-270, CE, Fortaleza, Brazil.
Coêlho
G R
GR
Coutinho
M C
MC
Silva
M M
MM
Angelim
E V
EV
Menezes
D B
DB
Fonteles
M C
MC
Monteiro
H S
HS
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007213:Indomethacin / Q000627:therapeutic use*; D007444:Inulin / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010741:Phospholipases A / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D003907:Dexamethasone; D007444:Inulin; D012964:Sodium; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; C057862:cyanoginosin LR; D011188:Potassium; D007213:Indomethacin