Estudos dos mecanismos de ação de 2 derivados semissintéticos obtidos da moringa oleifera em ensaio pré-clinicos de dor na ATM de ratos

Abstract

Introduction: Temporomandibular disorders (TMDs), which represent the second cause of orofacial pain in clinical practice, comprise a heterogeneous group of musculoskeletal disorders involving the temporomandibular joint (TMJ). The most commonly used drugs are NSAIDs, but evidence of their efficacy in treating TMD is very limited, and their continued use can cause a number of undesirable side effects. Interest in the bioprospecting of substances derived from native plants has increased in recent decades. Moringa oleifera adapts especially well to the semiarid climate of northeastern Brazil. Studies have shown the ability of M. oleifera-derived isothiocyanates (ITCs) to inhibit the inflammatory process. In the research group developed 3 semisynthetic compounds, which generated the deposit of 3 patents, obtained from a compound extracted from the flowers of M. oleifera. Also, a study showed that these compounds do not present systemic toxicity and showed antinociceptive and anti-inflammatory properties. Objective: To evaluate the antinociceptive and anti-inflammatory mechanism of action of two semisynthetic compounds MC-D7 and MC-D9 obtained from MC-1 isoticianate isolated from M. oleifera flowers in the rat TMJ. Materials and Methods: Male Wister rats (weight 180-240g), orally treated with saline, MC-D7 (1 μg / kg) and MC-D9 (1ηg / kg) were used. After 60 min Intra-articular saline injection (50 μL, 0.9%) was applied to the control or formalin group (50 μL, 1.5%) in the left TMJ. Nociceptive response was assessed by the number of times (in seconds) of scratching the left TMJ region and the times that the head was reflexively raised within 45 min. In addition, the role of central opioid receptors, hemoxygenase-1 (HO-1) and NO / GMPc / PKG / K + ATP pathway in the antinociceptive mechanism of action of MC-D7 and MC-D9 was tested. Nociceptive behavior was evaluated for 45 min. To investigate the participation of HO-1 / GMPc / PKG / K + ATP and the NO / GMPc / PKG / K + ATP pathway, inhibitors ZnPP-IX, aminoguanidine, ODQ, KT5823 and glibenclamide were used 30 min before administration of MC-D7 (1μg / kg) or MC-D9 (1ηg / kg), respectively. To study opioid receptors, rats were pretreated (15 min) with intrathecal injection of naloxone opioid receptor inhibitor μ. Results and Discussion: Treatment with MC-D7 1 μg / kg and MC-D9 1 ηg / kg significantly decreased nociceptive behavioral outcome when compared to formalin group. The iNOS inhibitor aminoguanidine, ODQ and glibenclamide reversed the antinociceptive effect of MC-D9, but KT 5823 did not reverse the antinociceptive effect of MC-D9 on formalin-induced TM hypernociception. The HO-1 specific inhibitor (ZnPP-IX) reversed the antinociceptive effect of MC-D7 on formalin-induced TMJ hypernociception when compared to the MC-D7 group; ODQ reversed the MC-D7 effect when compared to the MC-D7 group alone; KT5823 and glibenclamide did not reverse the antinociceptive effect of MC-D7 on formalin-induced TMJ hypernociception. The non-selective opioid receptor antagonist naloxone did not reverse the effect of MC-D7 and MC-D9 statistically significantly when compared to MC-D7 and MC-D9, respectively. The selective hemeoxygenase-1 (HO-1) inhibitor ZnPP-IX did not reverse the antinociceptive effect of MC-D9 when compared to the MC-D9 group. Conclusion: The mechanisms involved in the antinociceptive effect of MC-D7 act peripherally via the HO-1 / cGMP pathway and MC-D9 also act peripherally via the NO / GMPc / K + ATP pathway. Keywords: Moringa oleifera; ear-jaw articulation; nociception; opioid receptors