Uma nova carboximidamina modula a nocicepção inflamatória e comportamento doentio em modelos experimentais in vivo

Abstract

Inflammation is a physiological and protective reaction of the human body, triggered by pathogens and tissue damage, which results in activation of the immune system. Among the clinical signs of inflammation, pain is the most unpleasant and leads to reduced quality of life for many people. The increase in proinflammatory cytokines during the course of an infection causes sick individuals to develop a set of adaptive behavioral changes, collectively referred to as sick behavior. Inflammation, therefore, has become an imperative therapeutic target for new pharmacological interventions. For the treatment of inflammation and pain, anti-inflammatory drugs are used in clinical practice, which, however, have several side effects and limited effectiveness, stimulating the search for new effective drugs with minimal side effects. Therefore, this research aimed to verify the pharmacological properties of a new carboximidamine, DCHA, in the modulation of nociception and inflammation in animal

models. The DCHA was used to evaluate the antinociceptive effects in mice by the acetic acid- induced abdominal contortions test, formalin test and hot plate test. The anti-inflammatory

effect of DCHA was evaluated on lipopolysaccharide (LPS) -induced sick behavior in mice by open-field and forced swimming tests. In addition, we also evaluated the expression of iNOS mRNA and proinflammatory cytokines (IL-β, TNF-α and IL-6) from the blood, liver and kidney of these animals by quantitative real time PCR. Locomotor activity was assessed in the open field test. The experiments were carried out with the proper approval of the Animal Use Ethics Committee of the Federal University of Amazonas, with the process number 037/2018. DCHA reduced the number of acetic acid-induced contortions and paw licking time in both phases of the formalin test, as well as increased latency time in the hot plate test. Combining the results of chemical and thermal nociception models, it can be suggested that the substance has peripherally and centrally mediated antinociceptive effect. The administration of lipopolysaccharide (LPS, 100 μg / kg, ip) induced behavioral changes in mice, observed by increasing the time it spent floating in the forced swimming test and decreasing the locomotor and exploratory activity in the open field test, as well as increasing iNOS mRNA expression

and pro-inflammatory cytokines IL-1β, TNF-α and IL-6. DCHA pretreatment attenuated LPS- induced behavioral changes as well as significantly reduced expression of iNOS and

proinflammatory cytokines in mice. The experimental results of the present study showed that

the substance DCHA showed antinociceptive and anti-inflammatory effects in vivo. The anti- inflammatory effect obtained suggest to be due to the reduction of proinflammatory cytokines. Finally, the results lead to the pharmacological potential of the substance as a new anti- inflammatory drug.