title: Pyritinol reduces nociception and oxidative stress in diabetic rats.
abstract: The purpose of this study was to assess the antinociceptive and antiallodynic effect of pyritinol as well as its possible mechanism of action in diabetic rats. Streptozotocin (50 mg/kg) injection caused hyperglycemia within 1 week. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Oral acute administration of pyritinol (50-200 mg/kg) dose-dependently reduced flinching behavior in diabetic rats. Moreover, prolonged administration of pyritinol (12.5-50 mg/kg, every 2 days for 2 weeks) reduced formalin-induced nociception. 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor, 2 mg/kg, i.p.), but not naltrexone (a non-selective opioid receptor antagonist, 1 mg/kg, s.c.) or indomethacin (a non-selective cycloxygenase inhibitor, 5 mg/kg, i.p.), blocked the pyritinol-induced antinociception in diabetic rats. Given alone ODQ, naltrexone or indomethacin did not modify formalin-induced nociception in diabetic rats. Oral acute (200 mg/kg) or prolonged (25 mg/kg, every 2 days for 2 weeks) administration of pyritinol significantly reduced streptozotocin-induced changes in free carbonyls, dityrosine, malondialdehyde and advanced oxidative protein products. Four to 8 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, oral administration of pyritinol (50-200 mg/kg) reduced tactile allodynia in diabetic rats. Results indicate that pyritinol is able to reduce formalin-induced nociception and tactile allodynia in streptozotocin-injected rats. In addition, data suggest that activation of guanylyl cyclase and the scavenger properties of pyritinol, but not improvement in glucose levels, play an important role in these effects.
authors.affiliation: Escuela de Biología, Benemérita Universidad Autónoma de Puebla, Puebla, Puebla, Mexico.
authors.forename: Guillermina Yanek
authors.initials: GY
authors.lastname: Jiménez-Andrade
authors.forename: Gerardo
authors.initials: G
authors.lastname: Reyes-García
authors.forename: Gabriela
authors.initials: G
authors.lastname: Sereno
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ceballos-Reyes
authors.forename: Guadalupe C
authors.initials: GC
authors.lastname: Vidal-Cantú
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D011746:Pyrithioxin / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000700:Analgesics; D010069:Oxadiazoles; D011810:Quinoxalines; D009271:Naltrexone; D013311:Streptozocin; D011746:Pyrithioxin; D007213:Indomethacin