Tawfik Dina Ibrahim, Osman Afaf Sayed, Tolba Hedayat Mahmoud, Khattab Aida, Abdel-Salam Lubna O, Kamel Mahmoud M
Pharmacology Department, October 6 University, Eqypt.
Medical Pharmacology Department, Faculty of Medicine, Cairo University, Eqypt.
Neuropeptides. 2016 Oct;59:39-45. doi: 10.1016/j.npep.2016.06.003. Epub 2016 Jun 22.
Crohn's disease is a relapsing inflammatory condition afflicting the digestive tract. Drugs used for treatment of Crohn's disease may be associated with serious side effects. Endogenous opioid peptides modulate inflammatory cytokine production. Opioid antagonists have been shown to play a role in healing and repair of tissues. This work was designed to detect the possible beneficial effects of opioid antagonist naltrexone in indomethacin-induced Crohn's disease in rats.
Enteritis was induced in male albino rats by two subcutaneous injection of indomethacin in a dose of 7.5mg/kg 24h apart started on day one. Salfasalazine, naltrexone and their combination were administered orally from day one of induction of enteritis to day 10. Disease activity index, serum levels of C-reactive protein and tumor necrosis factor-α, macroscopic and microscopic pathological scores and in vitro motility studies were evaluated.
Induction of enteritis resulted in significant increase of disease activity index, significant elevation of serum levels of C-reactive protein and tumor necrosis factor-α, significant deterioration of pathological scores and significant increase in the mean contractility response of the isolated ileal segments compared with normal untreated rats. Treatment with sulfasalazine, low dose of natrexone or their combination resulted in significant improvement of all measured parameters compared with enteritis group.
The current finding could provide new interesting opportunity for developing new therapeutic approaches for treatment of Crohn's disease. Use of naltrexone, especially in small dose, has little side effects making it of interest for treatment of Crohn's disease. Also, it provides the possibility of reduced doses of other drugs if it is used as combined therapy.
克罗恩病是一种折磨消化道的复发性炎症性疾病。用于治疗克罗恩病的药物可能会伴有严重的副作用。内源性阿片肽可调节炎性细胞因子的产生。阿片拮抗剂已被证明在组织愈合和修复中发挥作用。本研究旨在检测阿片拮抗剂纳曲酮对吲哚美辛诱导的大鼠克罗恩病可能产生的有益作用。
从第1天开始，每隔24小时给雄性白化病大鼠皮下注射两次剂量为7.5mg/kg的吲哚美辛，诱导肠炎。从肠炎诱导的第1天到第10天，口服柳氮磺胺吡啶、纳曲酮及其组合药物。评估疾病活动指数、血清C反应蛋白和肿瘤坏死因子-α水平、大体和显微镜下病理评分以及体外运动性研究。
与正常未治疗的大鼠相比，肠炎诱导导致疾病活动指数显著增加、血清C反应蛋白和肿瘤坏死因子-α水平显著升高、病理评分显著恶化以及离体回肠段平均收缩反应显著增加。与肠炎组相比，柳氮磺胺吡啶、低剂量纳曲酮或它们的组合治疗可使所有测量参数显著改善。
目前的研究结果可为开发治疗克罗恩病的新治疗方法提供新的有趣机会。使用纳曲酮，尤其是小剂量使用，副作用很小，使其成为治疗克罗恩病的一个有吸引力的选择。此外，如果作为联合疗法使用，它还提供了减少其他药物剂量的可能性。
