Renal effects of supernatant from rat peritoneal macrophages activated by microcystin-LR: role protein mediators.
We have demonstrated previously that microcystin-LR promoted some renal alterations using the isolated perfused rat kidney preparation. However, these effects were not proved to be direct or indirect. The aim of the current work is to examine the renal effects promoted by supernatants from rat macrophages stimulated with microcystin-LR and the role of inflammatory mediators. Peritoneal macrophages were collected previously and were incubated for 1h in fresh medium (control) and in medium containing microcystin-LR. Dexamethasone, quinacrine, thalidomide and cycloheximide were administered 30 min before microcystin-LR. Supernatants of macrophages stimulated with or without pharmacological inhibitors were added on the perfused rat kidney model. The infusion of macrophages supernatants stimulated by microcystin-LR caused significant increases in renal vascular resistance (C: 4.93+/-0.33 vs T: 5.15+/-0.21), glomerular filtration rate (C: 0.559+/-0.008 vs T: 0.978+/-0.15) and urinary flow (C: 0.16+/-0.01 vs T: 0.23+/-0.03). Cycloheximide, quinacrine and dexamethasone blocked these effects and thalidomide blocked renal vascular resistance. Macrophages stimulated by microcystin-LR release mediators capable of promoting nephotoxicity in isolated perfused rat kidney. Phospholipase A(2), TNF-alpha and other protein mediators appear to be involved on its renal toxic mechanism.
Nobre
A C L
AC
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Rua Cel Nunes de Melo, 1127, Fortaleza, CE 60430-270, Brazil.
Martins
A M C
AM
Havt
A
A
Benevides
C
C
Lima
A A M
AA
Fonteles
M C
MC
Monteiro
H S A
HS
D000818:Animals; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004338:Drug Combinations; D005260:Female; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010477:Perfusion; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D017077:Culture Media, Conditioned; D004338:Drug Combinations; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D013792:Thalidomide; D003907:Dexamethasone; D003513:Cycloheximide; C057862:cyanoginosin LR; D011796:Quinacrine