title: Anti-inflammatory and Anti-nociceptive Activity of Ruthenium Complexes with Isonicotinic and Nicotinic Acids (Niacin) as Ligands.
abstract: This work evaluated the analgesic and anti-inflammatory activity of ruthenium(II) complexes trans-[Ru(NO(+))(NH3)4(L)](BF4)3 and [Ru(NH3)5(L)](BF4)3 containing the nonsteroidal anti-inflammatory drugs nicotinic acid (Hnic) and its isomer isonicotinic acid (ina) as ligands (L). The anti-nociceptive potential of these complexes and the free ligands (noncoordinated to ruthenium) was tested in different models with doses ranging from 1 to 100 μmol/kg. The ligands themselves were inactive; however, the ruthenium complexes containing Hnic and ina inhibited mechanical hyperalgesia induced by prostaglandin E2, carrageenan-induced hyperalgesia, and antigen-induced arthritis. Moreover, the ruthenium complexes inhibited overt nociception induced by formalin, acetic acid, capsaicin, and cinnamaldehyde. The mechanism involved in the anti-nociceptive effects of the ruthenium complexes suggested that ATP-sensitive K(+) channel pathways were not involved because glibenclamide did not affect their anti-nociceptive activities. However, the anti-nociceptive effect appears to be a consequence of the reduction in neutrophil migration and inhibition of the protein kinase C pathway.
authors.affiliation: †Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, CEP 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Cristina S
authors.initials: CS
authors.lastname: Freitas
authors.affiliation: ‡Instituto de Química de São Carlos, Universidade de São Paulo-USP, P.O. Box 780, CEP 13566-590, São Carlos, SP, Brazil.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Roveda
authors.affiliation: ‡Instituto de Química de São Carlos, Universidade de São Paulo-USP, P.O. Box 780, CEP 13566-590, São Carlos, SP, Brazil.
authors.forename: Daniela R
authors.initials: DR
authors.lastname: Truzzi
authors.affiliation: ‡Instituto de Química de São Carlos, Universidade de São Paulo-USP, P.O. Box 780, CEP 13566-590, São Carlos, SP, Brazil.
authors.forename: André C
authors.initials: AC
authors.lastname: Garcia
authors.affiliation: †Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, CEP 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Cunha
authors.affiliation: †Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, CEP 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: ‡Instituto de Química de São Carlos, Universidade de São Paulo-USP, P.O. Box 780, CEP 13566-590, São Carlos, SP, Brazil.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Franco
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002351:Carrageenan / Q000633:toxicity; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D007539:Isonicotinic Acids / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D015394:Molecular Structure; D009539:Nicotinic Acids / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D017975:Ruthenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D007539:Isonicotinic Acids; D009539:Nicotinic Acids; D017975:Ruthenium Compounds; D002351:Carrageenan