Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Inflammation. 2019 Dec;42(6):2056-2064. doi: 10.1007/s10753-019-01068-0.
Escitalopram, a drug of choice in the treatment of depression, was recently shown to possess an anti-inflammatory activity. The aim of the present study was to elucidate the effect of escitalopram on peripheral inflammatory cascades in iodoacetamide-induced colitis associated with depressive behavior in ovariectomized rats. Moreover, the role of α-7 nicotinic acetylcholine receptor in mediating the anti-colitic effect of escitalopram was examined using a nicotinic receptor antagonist methyllycaconitine citrate. Colitis was induced by intracolonic injection of 4% iodoacetamide in ovariectomized rats. Escitalopram (10 mg/kg/day, i.p.) was then injected for 1 week and several parameters including macroscopic (colon mass index and ulcerative area), microscopic (histopathology and scoring), and biochemical (myeloperoxidase and tumor necrosis factor-α) were determined. Colitis induction in ovariectomized rats resulted in a marked increase in colon mass index, ulcerative area, histopathological scoring, myeloperoxidase activity and tumor necrosis factor-α levels. These effects were ameliorated by escitalopram, even in the presence of methyllycaconitine indicating that α-7 nicotinic acetylcholine receptor does not mediate the anti-inflammatory effect of escitalopram. The present study revealed the beneficial effect of escitalopram in iodoacetamide induced colitis in ovariectomized rats and suggests that it may represent a new therapeutic agent for the treatment of inflammatory bowel disease, especially in patients with or at high risk of depressive behavior.
依地普仑是治疗抑郁症的首选药物，最近研究发现其具有抗炎活性。本研究旨在阐明依地普仑对碘乙酰胺诱导的结肠炎相关抑郁行为的卵巢切除大鼠外周炎症级联的影响。此外，使用烟碱受体拮抗剂甲基戊二烯烟碱柠檬酸来研究α-7 烟碱型乙酰胆碱受体在介导依地普仑抗结肠炎作用中的作用。通过向卵巢切除大鼠的结肠内注射 4%碘乙酰胺来诱导结肠炎。然后，每天腹腔注射依地普仑（10mg/kg）1 周，并测定包括宏观（结肠质量指数和溃疡面积）、微观（组织病理学和评分）和生化（髓过氧化物酶和肿瘤坏死因子-α）在内的几个参数。卵巢切除大鼠的结肠炎诱导导致结肠质量指数、溃疡面积、组织病理学评分、髓过氧化物酶活性和肿瘤坏死因子-α水平显著增加。这些作用通过依地普仑得到改善，甚至在存在甲基戊二烯烟碱的情况下也是如此，表明α-7 烟碱型乙酰胆碱受体不介导依地普仑的抗炎作用。本研究揭示了依地普仑在卵巢切除大鼠碘乙酰胺诱导结肠炎中的有益作用，并表明它可能是治疗炎症性肠病的一种新的治疗剂，特别是在有或有抑郁行为高风险的患者中。
