Efeito antinociceptivo e anti-inflamatório de 4-fenilselenil-7-cloroquinolina em camundongos

Abstract

The development of new drugs for the treatment of painful and inflammatory clinical conditions remains of great interest, since pain is one of the most prevalent conditions, costly and disabling. Studies in the literature have shown that quinoline and organoselenium compounds have pharmacological properties against nociception and inflammation in animal models. Thus, the objective of this study was to evaluate the antinociceptive and anti-inflammatory actions of the 4-phenylselenyl- 7-chloroquinoline (4-PSQ), a quinoline containing selenium, in male adult Swiss mice. The antinociceptive potential of the compound was evaluated in writhing induced by acetic acid, hot plate and formalin tests. The time-response curve of the 4- PSQ was evaluated in writhing induced by acetic acid test. The antiedematogenic activity was evaluated in formalin-induced paw edema as well as in ear edema induced by croton oil. In parallel, it was determined the activity of the enzyme myeloperoxidase (MPO) and oxidative stress parameters in the ear of mice exposed to croton oil. It was evaluated the acute toxicity and the exploratory and locomotor activities of animals exposed to 4-PSQ. 4-PSQ (0.1 – 25 mg/kg), meloxicam (25 mg/kg, a reference drug) or vehicle were administered orally (p.o.) 30 minutes before acetic acid, formalin, hot-plate and open-field tests. 4-PSQ reduced the number of writhes induced by acetic acid, and caused an increase in latency time on the hot plate test. Furthermore, the administration of 4-PSQ inhibited both neurogenic and inflammatory phases and reduced the paw edema induced by formalin. Locomotor and exploratory activities in the open field test were not altered by treatments. The antinociceptive effect in inhibiting acetic acid-induced abdominal writhing of 4-PSQ started at 0.5 h and remained significant up to 4 h after administration. Since, nociceptive and inflammatory processes are interrelated and inflammation triggers the production of reactive species, anti-inflammatory and antioxidant properties of compound were investigated. Thus, 4-PSQ reduced edema formation, decreased the MPO activity and attenuated the reactive species leves induced by croton oil in the mice ear. The compound also partially protect against reduction of 2,2'-azinobis-3- ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) levels induced by croton oil. 4-PSQ presented similar results for meloxicam in evaluated tests. Moreover, administration of the compound in mice did not cause acute hepatic and renal toxicities. From this result, it could be suggested that 4-PSQ exerts antinociceptive and anti-inflammatory acute actions in mice. Thus, 4-PSQ may represent a promising alternative for the development of future therapeutic strategies for pain and inflammation.