Mediators involved in the febrile response induced by Tityus serrulatus scorpion venom in rats.
Tityus serrulatus venom (Tsv) was intraperitoneally (ip) injected at doses of 75, 150 and 300mug/kg and IL-1beta (2.0 microg/kg) was given intravenously (iv) to male Wistar rats. Rectal temperature was measured by radiotelemetry. Vagotomy was performed according to Bluthe et al. [1994. Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. C R Acad. Sci. 317(6), 499-503]. Cerebrospinal fluid (CSF) and peritoneal fluid (PF) levels of bradykinin (BK) were measured by ELISA. B(1) (des-Arg(9)-[Leu(8)]-BK; DALBK) and B(2) kinin receptor (icatibant) antagonists (1.0 mg/kg each), the induced nitric oxide synthase inhibitor aminoguanidine (50.0 mg/kg), the neuronal nitric oxide synthase inhibitor 7-nitroindazole (30.0 mg/kg), the dual cyclooxygenase inhibitor ibuprofen (10.0 mg/kg), the selective interleukin-1 receptor antagonist IL-ra (2.0 mg/kg) and dipyrone (120 mg/kg) were given ip. Celecoxib (5 mg/kg) was given per os (po). Tsv at doses of 75 microg/kg evoked no change in rectal temperature while at doses of 150 and 300 microg/kg it promoted long-lasting fever (2 degrees C+/-0.1). Tsv (150 microg/kg) increased by nearly 3 and 5 times, respectively BK concentration in the CSF and in the PF. Subdiaphragmatic vagotomy or 7-nitroindazole reduced, icatibant, DALBK, IL-1ra, aminoguanidine and dipyrone abolished, while ibuprofen and celecoxib failed to affect Tsv-induced fever. These results suggest that PGs do not play a relevant role, whereas, kinins via their B(1) and B(2) receptors, IL-1, nitric oxide and vagal neurotransmission are involved in Tsv-induced fever.
Pessini
Andréa C
AC
Laboratório de Farmacologia, Faculdade de Cincias Farmacêuticas de Ribeirão Preto, USP, Av. do Café, s/n Campus USP, 14040-903 Ribeirão Preto, SP, Brasil.
Santos
Danielle R
DR
Arantes
Eliane C
EC
Souza
Glória E P
GE
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry; D001831:Body Temperature / Q000187:drug effects; D001920:Bradykinin / Q000134:cerebrospinal fluid; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology; D007191:Indazoles / Q000494:pharmacology; D018836:Inflammation Mediators / Q000494:pharmacology / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000633:toxicity*; D012605:Scorpions; D013686:Telemetry; D014628:Vagotomy
D018712:Analgesics, Non-Narcotic; D007191:Indazoles; D018836:Inflammation Mediators; D007375:Interleukin-1; D009498:Neurotoxins; D012604:Scorpion Venoms; C003609:tityustoxin; D001920:Bradykinin; C080122:7-nitroindazole