Effects of type II pyrethroid cyhalothrin on peritoneal macrophage activity in rats.
Synthetic type II pyrethroids induce anxiety, immunosuppressive or, alternatively, immunostimulatory effects in laboratory animals. Macrophages are known to be key elements in cellular immune responses. The present study was designed to investigate the in vivo effects of cyhalothrin (0.6, 1.0 and 3.0 mg/kg/once daily for 7 days) on macrophage activity. The in vitro effects of cyhalothrin (100 nM, 1 and 10 microM) were also analyzed to verify a possible direct action of this pyrethroid on macrophage. Results showed that in vivo cyhalothrin treatment: (1) decreased macrophage spreading and phagocytosis indexes; (2) decreased macrophage nitric oxide (NO) production; (3) did not change spontaneous or PMA-induced macrophage H2O2 release. The no effect level dose (NOEL) obtained for cyhalothrin on macrophage activity was 0.6 mg/kg/day. In-vitro data showed that cyhalothrin decreased (1) macrophage NO production and (2) macrophage spontaneus and PMA-induced H2O2 releases. The present results were explained through an indirect action for cyhalothrin on macrophage activity via hypothalamic pituitary adrenals (HPA) axis activation. A direct effect for cyhalothrin on macrophage, most probably through an action on Na+ membrane channels, was also suggested. Finally, it is possible that both direct and indirect mechanisms would be involved with cyhalothrin effects on macrophage activity.
Righi
D A
DA
Applied Pharmacology and Toxicology Laboratory, School of Veterinary Medicine, University of São Paulo, São Paulo, SP 05508-900, Brazil.
Palermo-Neto
J
J
D000818:Animals; D006861:Hydrogen Peroxide / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D008297:Male; D009163:Mycobacterium bovis; D009569:Nitric Oxide / Q000378:metabolism; D009570:Nitriles / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D010587:Phagocytosis / Q000187:drug effects; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; C037304:cyhalothrin