Contribuição dos sistemas serotoninérgico e nitrérgico no efeito antinociceptivo e efeito anti-inflamatório em modelo de pleurisia de 7-cloro-4- (fenilseleno)quinolina em camundongos

Abstract

A new quinoline containing selenium, 4-phenylselenyl-7-chloroquinoline (4-PSQ), was described and synthetized by our research group. Recently, we demonstrated the potential antinociceptive and anti-inflammatory of 4-PSQ. For this reason, the first objective of this study was extending our previous findings by investigating the contribution of serotonergic and nitrergic systems in the acute antinociceptive action of this compound in Swiss mice. The pretreatment with WAY100635 (0.7 mg/kg, intraperitoneally (i.p.), a selective antagonist of 5-HT1A receptor), ketanserin (0.3 mg/kg, i.p., a selective antagonist of 5-HT2A receptor) and pindolol (1 mg/kg, i.p., a nonselective antagonist of 5-HT1A/1B receptors) partially blocked the antinociceptive effect caused by 4-PSQ (25 mg/kg, per oral, p.o.) in the acetic acid-induced abdominal writhing test. Nitric oxide precursor, L- arginine hydrochloryde (L-arginine, 600 mg/kg, i.p.), partially reversed antinociception caused by 4-PSQ or ω-nitro-L-arginine (L-NOARG, 75 mg/kg, i.p.). Furthermore, treatments did not modify locomotor and exploratory activities of mice. Additionally, acute anti-inflammatory effect of 4- PSQ in a model of pleurisy induced by carragenan was investigated in mice. 4-PSQ reduced the cellular migration, pleural exudate accumulation and myeloperoxidase activity induced by carragenan exposure. Additionally, 4-PSQ protected against the increase in reactive species levels and reduction of nonprotein thiols levels induced by carragenan. These data suggest that 4-PSQ has therapeutical potential for acute inflammation. Data presented here showed that the modulation of serotonergic and nitrergic systems contributed to the antinociceptive effect of 4-PSQ.