Mediators involved in the febrile response induced by Tityus serrulatus scorpion venom in rats

Toxicon. 2006 Oct;48(5):556-66. doi: 10.1016/j.toxicon.2006.07.006. Epub 2006 Jul 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Non-Narcotic / pharmacology
  • Animals
  • Ascitic Fluid / chemistry
  • Body Temperature / drug effects
  • Bradykinin / cerebrospinal fluid
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Fever / chemically induced*
  • Fever / physiopathology
  • Indazoles / pharmacology
  • Inflammation Mediators / pharmacology
  • Inflammation Mediators / physiology*
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Interleukin-1 / pharmacology
  • Male
  • Neurotoxins / toxicity*
  • Rats
  • Rats, Wistar
  • Scorpion Venoms / toxicity*
  • Scorpions*
  • Telemetry
  • Vagotomy

Substances

  • Analgesics, Non-Narcotic
  • Indazoles
  • Inflammation Mediators
  • Interleukin-1
  • Neurotoxins
  • Scorpion Venoms
  • tityustoxin
  • Bradykinin
  • 7-nitroindazole