Se - [(2,2-Dimethyl-1,3-dioxolan-4-yl) methyl] 4-chlorobenzoselenolate reduces the nociceptive and edematogenic response by chemical noxious stimuli in mice: Implications of multi-target actions

Background: The present study evaluated the antioxidant, antinociceptive and anti-edematogenic effects of Se-[(2,2-dimethyl-1,3-dioxolan-4-yl) methyl] 4-chlorobenzoselenolate (Se-DMC). Methods: In vitro experiments were carried out to evaluate Se-DMC antioxidant action. Thiobarbituric acid reactive species levels, 2,2'-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-thylbenzthiazoline-6-sulfonic acid) radicals scavenging and glutathione S-transferase-like activity were determined. Male Swiss mice were orally pretreated with Se-DMC (1, 10 and 50 mg/kg), meloxicam (50 mg/kg) or vehicle 30 min prior to acetic acid or glutamate test. To extend our knowledge of the pharmacological properties of this compound, it was tested in an inflammatory model through ear edema induced by croton oil. The contribution of glutamatergic and serotonergic systems was also investigated. Results: In vitro experiments revealed that Se-DMC exerts antioxidant activity. Nociception induced by glutamate or acetic acid was reduced by Se-DMC or meloxicam. Se-DMC diminished the paw edema formation induced by glutamate, while meloxicam did not show any effect. Se-DMC and meloxicam decreased the ear edema formation and protected against the increase in myeloperoxidase activity in mice ear induced by croton oil. The pretreatment of animals with MK-801 did not alter antinociception caused by Se-DMC in the glutamate test. The antinociceptive effect exerted by Se-DMC in the acetic acid test was reverted by the pretreatment of mice with different serotonergic antagonists (WAY100635, ketanserin and pindolol). Conclusions: Data presented here showed that the modulation of serotonergic and glutamatergic systems and the anti-inflammatory and antioxidant actions could contribute to the antinociceptive and anti-edematogenic effects of Se-DMC and it supported the therapeutic potential of this compound. (C) 2019 Maj Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.