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 to expand our previous findings by investigating the contribution of glutamatergic, serotonergic, and nitrergic systems to the acute antinociceptive action of this compound. Pretreatment with 4-PSQ (0.01-25 mg/kg, p.o.) reduced the nociception induced by glutamate. MK-801 (an uncompetitive antagonist of the N-Methyl-d-aspartate (NMDA) receptor) blocked the antinociceptive effect exerted by 4-PSQ (25 mg/kg, p.o.) in the acetic acid-induced abdominal writhing test. The pretreatment with WAY100635 (a selective antagonist of 5-HT receptor), ketanserin (a selective antagonist of 5-HT receptor), and pindolol (a nonselective antagonist of 5-HT 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 hydrochloride, partially reversed antinociception caused by 4-PSQ or ω-nitro-l-arginine (l-NOARG). Treatments did not modify the locomotor and exploratory activities of mice. Additionally, the acute anti-inflammatory effect of 4-PSQ in a model of pleurisy induced by carrageenan in mice was investigated. 4-PSQ reduced the cellular migration, pleural exudate accumulation, and myeloperoxidase activity induced by carrageenan exposure. 4-PSQ protected against the increase in reactive species levels and reduction of nonprotein thiol levels induced by carrageenan. Data presented here showed that the modulation of serotonergic, nitrergic, and glutamatergic systems contributed to the antinociceptive effect of 4-PSQ and it reinforced the therapeutic potential of this quinolinic compound for acute inflammation.
This study investigated the effect of the topical treatment with meloxicam-loaded nanocapsules (M-NC) on symptoms, inflammatory response and oxidative parameters in an atopic dermatitis (AD) model in BALB/c mice. 2,4-Dinitrochlorobenzene (DNCB) was applied to the dorsal skin on days 1-3 for sensitization. Mice were challenged with DNCB on the ear (on days 14-29) and dorsal skin (on days 14, 17, 20, 23, 26, and 29). Treatments with blank nanocapsules (B-NC), free meloxicam (M-F) or M-NC were applied to the backs of the mice from days 14 to 29. On the day 30, skin severity scores and scratching behaviour were determined. After that, ears and dorsal skin were removed for determination of inflammatory parameters (edema and myeloperoxidase (MPO) activity) and oxidative parameters (thiobarbituric acid reactive species (TBARS) and non-protein thiol (NPSH) levels), respectively. DNCB increased the severity of skin lesions, scratching behaviour, edema and MPO activity of ears and dorsal skin TBARS levels. M-NC reversed skin severity scores, scratching behaviour and inflammatory response induced by DNCB. B-NC and M-F did not have effect in this model. In summary, meloxicam carried by polymeric nanocapsules reversed inflammatory response and ameliorated symptoms in an AD model.
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