TY - JOUR
T1 - Pyritinol reduces nociception and oxidative stress in diabetic rats
AU - Jiménez-Andrade, Guillermina Yanek
AU - Reyes-García, Gerardo
AU - Sereno, Gabriela
AU - Ceballos-Reyes, Guillermo
AU - Vidal-Cantú, Guadalupe C.
AU - Granados-Soto, Vinicio
N1 - Funding Information:
This work was done at the Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Sede Sur and at the Sección de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, D.F., Mexico. Authors greatly appreciate the bibliographic assistance of Héctor Vázquez. This work is part of the B.Sc. dissertation of Guillermina Yanek Jiménez-Andrade. Partially supported by Conacyt, grant 59879 (VGS) and C01-46187/A-1 (GC).
PY - 2008/8/20
Y1 - 2008/8/20
N2 - 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.
AB - 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.
KW - Diabetes
KW - Naltrexone
KW - Oxidative stress
KW - Pyritinol
KW - Tactile allodynia
UR - http://www.scopus.com/inward/record.url?scp=48049083320&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2008.06.050
DO - 10.1016/j.ejphar.2008.06.050
M3 - Artículo
C2 - 18593582
SN - 0014-2999
VL - 590
SP - 170
EP - 176
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -