Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; Faculty of Pharmacy, Aqaba University of Technology, Aqaba, Jordan.
Pharmacol Rep. 2019 Oct;71(5):774-781. doi: 10.1016/j.pharep.2019.04.005. Epub 2019 Apr 9.
Pirfenidone (PFD) is an orally active antifibrotic agent that has anti-inflammatory activity in diverse animal models. Its effect against acute pancreatitis (AP) has not been elucidated. Hence, the present investigation was carried out to assess the potential protective role of PFD against l-arginine-induced AP in mice.
AP was induced in adult male Swiss albino mice via intraperitoneal injections of l-arginine (4 g/kg, twice each 1 h apart). PFD (250 mg/kg, orally) was administered one day before and on the day of l-arginine challenge. Twenty-four hours after l-arginine injection, the severity of AP was evaluated using biochemical and histological analyses. Indices of oxidative stress, inflammation and apoptosis were evaluated using ELISA and immunohistochemistry (IHC).
PFD suppressed the development of l-arginine-induced AP as revealed by the improvement of histopathological lesions of pancreatic specimen and the significant reduction of serum amylase and lipase levels. Notably, PFD reduced the lipid peroxidation and enhanced the antioxidants such as reduced glutathione (GSH) and superoxide dismutase (SOD) in pancreatic tissue. Importantly, PFD suppressed AP-associated elevation of inflammatory cytokines along with depression of nuclear factor kappa-B (NF-κB) immuno-expression in pancreatic tissue. Lastly, PFD efficiently ameliorated AP-induced elevation of the pro-apoptotic protein (Bax) and increased AP-induced reduction of the anti-apoptotic protein (Bcl2).
PFD protected against l-arginine-induced AP in mice through anti-oxidative, anti-inflammatory and anti-apoptotic properties.
吡非尼酮（PFD）是一种具有抗炎活性的口服抗纤维化药物，在多种动物模型中均具有抗纤维化作用。但其对急性胰腺炎（AP）的作用尚未阐明。因此，本研究旨在评估 PFD 对小鼠 L-精氨酸诱导的 AP 的潜在保护作用。
通过腹腔内注射 L-精氨酸（4g/kg，两次，每次间隔 1 小时）诱导成年雄性瑞士白化病小鼠发生 AP。PFD（250mg/kg，口服）在 L-精氨酸挑战前一天和当天给药。在 L-精氨酸注射后 24 小时，通过生化和组织学分析评估 AP 的严重程度。通过 ELISA 和免疫组化（IHC）评估氧化应激、炎症和细胞凋亡的指标。
PFD 抑制了 L-精氨酸诱导的 AP 的发展，表现为胰腺标本的组织病理学损伤改善，血清淀粉酶和脂肪酶水平显著降低。值得注意的是，PFD 降低了胰腺组织中的脂质过氧化作用，并增强了还原型谷胱甘肽（GSH）和超氧化物歧化酶（SOD）等抗氧化剂。重要的是，PFD 抑制了与 AP 相关的炎症细胞因子的升高，同时抑制了胰腺组织中核因子 kappa-B（NF-κB）免疫表达的升高。最后，PFD 有效地改善了 AP 诱导的促凋亡蛋白（Bax）的升高，并增加了 AP 诱导的抗凋亡蛋白（Bcl2）的减少。
PFD 通过抗氧化、抗炎和抗凋亡特性对小鼠的 L-精氨酸诱导的 AP 具有保护作用。
