Sheikhzadeh Sanaz, Malekinejad Hassan, Hobbenaghi Rahim
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;
Department of Pathology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
Vet Res Forum. 2013 Spring;4(2):77-83.
Mycophenolate mofetil (MMF) as an immunosuppressive agent is used to prevent graft rejection. One of the adverse effects of long time administration of MMF is the gastrointestinal disorder. This study aimed to investigate the gastroprotective effect of silymarin (SMN) on MMF-induced gastrointestinal (GI) disorders. Twenty-four adult female Wistar rats were assigned into three groups including the control and test groups. The control animals received saline (5 mL kg(-1)) and the test animals were treated with MMF (40 mg kg(-1), orally) and saline, MMF and silymarin (SMN, 50 mg kg(-1), orally) for 14 consecutive days, respectively. To evaluate the GI disorders due to the MMF-induced oxidative stress and subsequently the protective effect of SMN, malondialdehyde (MDA), total thiol molecules (TTM) levels and total anti-oxidant capacity (TAC) were determined. Additionally, histopathological examinations in the duodenal region of small intestine were performed. The MMF-increased level of MDA was reduced by SMN administration, while the MMF-reduced level of TTM increased significantly (p < 0.05) by SMN administration. Histopathological examinations showed the goblet cell reduction and congestion in the MMF-received animals; while SMN was able to improve the MMF-induced goblet cell reduction and congestion. Our data suggest that the MMF-induced GI disorders are characterized by changes in antioxidant status, which presented by the elevation of MDA level and reduction of TTM concentration. Moreover, the improved biochemical alterations and histopathologic damages by SMN indicating its gastroprotective and antioxidant effects.
霉酚酸酯（MMF）作为一种免疫抑制剂用于预防移植物排斥反应。长期服用MMF的不良反应之一是胃肠道紊乱。本研究旨在探讨水飞蓟素（SMN）对MMF诱导的胃肠道（GI）紊乱的胃保护作用。将24只成年雌性Wistar大鼠分为三组，包括对照组和试验组。对照组动物接受生理盐水（5 mL kg⁻¹），试验组动物分别连续14天口服MMF（40 mg kg⁻¹）和生理盐水、MMF和水飞蓟素（SMN，50 mg kg⁻¹）。为了评估MMF诱导的氧化应激导致的胃肠道紊乱以及随后SMN的保护作用，测定了丙二醛（MDA）、总硫醇分子（TTM）水平和总抗氧化能力（TAC）。此外，还对小肠十二指肠区域进行了组织病理学检查。给予SMN可降低MMF升高的MDA水平，而给予SMN可使MMF降低的TTM水平显著升高（p < 0.05）。组织病理学检查显示，接受MMF的动物杯状细胞减少和充血；而SMN能够改善MMF诱导的杯状细胞减少和充血。我们的数据表明，MMF诱导的胃肠道紊乱的特征是抗氧化状态的变化，表现为MDA水平升高和TTM浓度降低。此外，SMN改善了生化改变和组织病理学损伤，表明其具有胃保护和抗氧化作用。
