Mousavi Seyyedeh Elaheh, Saberi Pegah, Ghasemkhani Naeemeh, Fakhraei Nahid, Mokhtari Rezvan, Dehpour Ahmad Reza
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
J Pharm Pharm Sci. 2018;21(1):184-194. doi: 10.18433/jpps29770.
Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, possesses antioxidant, antiapoptotic, neuroprotective, and anti-inflammatory properties. The aim of the present study was to investigate the effect of licofelone on lipopolysaccharide (LPS)-induced depression in a mouse model and also a possible role for nitric oxide (NO).
To elucidate the role of NO on this effect of licofelone (5 and 20 mg/kg, i.p.), L-NAME, a non-specific NO synthase (NOS) inhibitor; aminoguanidine (AG), a specific inducible NOS (iNOS) inhibitor; 7-nitroindazole (7-NI) a preferential neuronal NOS inhibitor (nNOS) and; L-arginine (L-Arg), as a NO donor, were used. The animal's behaviors were evaluated employing forced swimming test (FST), tail suspension test (TST) and open field test (OFT).
LPS (0.83 mg/kg, i.p.) induced depressive-like behavior increasing immobility time in FST and TST. Conversely, licofelone (20 mg/kg i.p.) reversed the depressive effect of LPS and lowered the immobility time in FST and TST. On the other hand, pretreatment with L-Arg also reversed the antidepressant-like effect of licofelone (20 mg/kg) in FST and TST. On the other hand, L-NAME (10 and 30 mg/kg), AG (50 and 100 mg/kg) and 7-NI (60 mg/kg) could potentiate licofelone (5 mg/kg) and lowered the immobility duration.
NO down-regulation possibly through iNOS and nNOS inhibition may involve in the antidepressant property of licofelone. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
利考昔酮是一种双环氧合酶/5-脂氧合酶抑制剂，具有抗氧化、抗凋亡、神经保护和抗炎特性。本研究的目的是研究利考昔酮对脂多糖（LPS）诱导的小鼠模型抑郁的影响以及一氧化氮（NO）可能发挥的作用。
为阐明NO在利考昔酮（5和20mg/kg，腹腔注射）这一作用中的角色，使用了L-NAME（一种非特异性一氧化氮合酶（NOS）抑制剂）、氨基胍（AG，一种特异性诱导型NOS（iNOS）抑制剂）、7-硝基吲唑（7-NI，一种优先作用于神经元NOS抑制剂（nNOS））以及L-精氨酸（L-Arg，作为一种NO供体）。采用强迫游泳试验（FST）、悬尾试验（TST）和旷场试验（OFT）评估动物行为。
LPS（0.83mg/kg，腹腔注射）诱导出抑郁样行为，增加了FST和TST中的不动时间。相反，利考昔酮（20mg/kg腹腔注射）逆转了LPS的抑郁作用，并缩短了FST和TST中的不动时间。另一方面，用L-Arg预处理也逆转了利考昔酮（20mg/kg）在FST和TST中的抗抑郁样作用。另一方面，L-NAME（10和30mg/kg）、AG（50和100mg/kg）和7-NI（60mg/kg）可增强利考昔酮（5mg/kg）的作用并缩短不动持续时间。
通过抑制iNOS和nNOS可能导致的NO下调可能与利考昔酮的抗抑郁特性有关。本文接受发表后评论。注册读者（见“致读者”）可通过点击本期目录页上的摘要进行评论。
