title: Antinociceptive and anti-hyperalgesic effects of bis(4-methylbenzoyl) diselenide in mice: evidence for the mechanism of action.
abstract: BACKGROUND
  The organoselenium compounds have been described to demonstrate several biological activities, including pain management.
  
  
  OBJECTIVE
  This study investigated the antinociceptive, hyperalgesic, and toxic effects of oral administration of bis(4-methylbenzoyl) diselenide (BMD) in mice.
  
  
  METHODS
  The antinociceptive and anti-hyperalgesic effects of BMD (1, 5, 10, 25, and 50 mg/kg, p.o.) were evaluated using models of nociception: formalin, capsaicin, bradykinin (BK), cinnamaldehyde, phorbol myristate acetate (PMA), 8-bromo-cAM, and glutamate-induced nociception; and mechanical hyperalgesia induced by carrageenan (Cg) or complete Freund's adjuvant (CFA). The acute toxicity was evaluated by biochemical markers for hepatic and renal damages.
  
  
  RESULTS
  BMD significantly inhibited the licking time of the injected paw in the early and late phases of a formalin test with ED50 values of 14.2 and 10.8 mg/kg, respectively. This compound reduced nociception produced by capsaicin (ED50 of 32.5 mg/kg), BK (ED50 of 24.6 mg/kg), glutamate (ED50 of 28.7 mg/kg), cinnamaldehyde (ED50 of 18.9 mg/kg), PMA (ED50 of 9.6 mg/kg), and 8-bromo-cAMP (ED50 of 24.8 mg/kg). In the glutamate test, the pretreatment with nitric oxide (NO) precursor, L-arginine, reversed antinociception caused by BMD or N(ω)-nitro-L-arginine (L-NOARG), but the effect of BMD was not abolished by naloxone. Mechanical hyperalgesia induced by Cg and CFA was attenuated by BMD, 70 ± 4% and 65 ± 4%, respectively. Furthermore, a single oral dose of BMD did not change plasma aspartate (AST) and alanine aminotransferase (ALT) activities or urea and creatinine levels.
  
  
  CONCLUSIONS
  BMD demonstrated as a promising compound because of the antinociceptive and anti-hyperalgesic properties in mice.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Pampa (UNIPAMPA), Campus Uruguaiana , Uruguaiana, RS , Brazil .
authors.forename: Franciele
authors.initials: F
authors.lastname: Donato
authors.forename: Natasha Frasson
authors.initials: NF
authors.lastname: Pavin
authors.forename: André Tiago Rossito
authors.initials: AT
authors.lastname: Goes
authors.forename: Leandro Cattelan
authors.initials: LC
authors.lastname: Souza
authors.forename: Letiére Cabreira
authors.initials: LC
authors.lastname: Soares
authors.forename: Oscar Endrigo Dorneles
authors.initials: OE
authors.lastname: Rodrigues
authors.forename: Cristiano Ricardo
authors.initials: CR
authors.lastname: Jesse
authors.forename: Lucielli
authors.initials: L
authors.lastname: Savegnago
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; D016566:Organoselenium Compounds; D020011:Protective Agents; C583859:bis(4-methylbenzoyl)diselenide
keywords: Organoselenium; pain; selenium; toxicity