Receptores opioides e enzima hemeoxigenase-1 medeiam antinocicepção de um derivado semissintético (MC-H) obtido a partir de um isotiocianato isolado das flores da moringa oleifera em modelo de dor na atm de ratos

Abstract

Moringa oleifera is a widely distributed tropical plant with nutritional and pharmac eutical properties extensively studied in the medical literature. This study aimed to investigate antinociceptive and anti-inflammatory effect of a semisynthetic molecule 4-[(2 ', 3', 4'-Otriacetyl -α-L-raminyloxy)N-benzyl]hydrazinecarbothioamide (MC-H) derived of 4-(4′-Oacetyl-α-L-rhamnosyloxy)benzylisothiocyanate (MC-1) obtained from M. oleifera flowers, in formalin-induced TMJ inflammatory hypernociception. In addition, it was tested the role of central opioid receptors, hemioxygenase-1 (HO-1) and NO/cGMP/PKG/K + ATP pathway in mechanism of MC-H antinociception. Male Wistar rats (180-240 g, n = 5) were pretreated (p.o.) with MC-H (0.0001; 0.01 or 1 μg/kg) 1 h prior to intra-articular injection of formalin (1,5%/50 μl) in the left TMJ. Nociceptive behavior was evaluated for 45 min. Periarticular tissues were removed for dosing of ICAM-1 and CD55 proteins involved in leucocyte adhesion by Western Blotting. The anti-inflammatory effect was measured by plasma extravasation of Evans Blue dye. To investigate participation of HO-1 and NO/cGMP/PKG/K + ATP pathway, inhibitors ZnPPIX, aminoguanidine, ODQ, KT5823 and glibenclamide were used 30 min prior to MC -H administration, respectively. To study the involvement of opioid receptors, rats were pretreated (15 min) with intrathecal injection of non-selective inhibitor naloxone or with CTOP, naltrindole and norbinaltorphimine, which are selective opioid receptor antagonists μ, δ and κ, respectively. The rotarod test evaluated the animal motor impairment. MC-H significantly reduced nociceptive behavior, reaching higher dose effect at 1 μg/kg (p <0.001). Similarly, MCH (1 μg/kg) abolished plasma extravasation and significantly reduced the expression of ICAM -1 and CD55 in periarticular tissues. The applications of ZnPP-IX, naloxone, CTOP and naltrindole reversed the antinociceptive effect of MC-H. There were no significant motor deficits. Therefore, MC-H has antinociceptive and anti-inflammatory effect in rats TMJ mediated peripherally by HO-1 and centrally by μ and δ opioid receptors.