Nader Manar A, Wagih Heba M
Department of Pharmacology and Toxicology, Colleague of Pharmacy, Taibah University, Almadinah Almunawwarah, 30001, Saudi Arabia.
Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2017 Mar;390(3):291-300. doi: 10.1007/s00210-016-1327-2. Epub 2016 Dec 14.
This investigation explored the nilotinib action in the management of acute pancreatitis (AP) and AP-induced lung and liver injury. AP was induced in Sprague Dawley (SD) rats with L-arginine. Treatment with nilotinib with or without L-arginine was applied for 7 days. Marked deterioration in serum amylase, lipase, aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH), nitric oxide (NO), total protein content, and transforming growth factor beta1 (TGF-β1) along with pancreatic, hepatic, and pulmonary tissue lipid peroxidation (MDA) after induction of AP while significant reduction in tissues superoxide dismutase (SOD), glutathione (GSH) with marked edema, hemorrhage, and perivascular inflammation with acinar cell necrosis, along with elevated pancreatic percentage expression of TGF-β1 and nuclear factor kappa B (NF-κB), were observed in the AP group. Nilotinib markedly ameliorated biochemical and histopathologic changes during AP, thus preserving the pancreas, liver, and lung histologically through mechanism involving antioxidant and anti-inflammatory actions.
本研究探讨了尼罗替尼在急性胰腺炎（AP）及其所致肺和肝损伤治疗中的作用。采用L-精氨酸诱导Sprague Dawley（SD）大鼠发生AP。尼罗替尼单独或联合L-精氨酸给药7天。AP诱导后，血清淀粉酶、脂肪酶、天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、乳酸脱氢酶（LDH）、一氧化氮（NO）、总蛋白含量及转化生长因子β1（TGF-β1）显著恶化，同时胰腺、肝脏和肺组织脂质过氧化（MDA）增加，而组织超氧化物歧化酶（SOD）、谷胱甘肽（GSH）显著降低，伴有明显水肿、出血及血管周围炎症和腺泡细胞坏死，且胰腺组织中TGF-β1和核因子κB（NF-κB）的表达百分比升高，这些变化在AP组中均有观察到。尼罗替尼显著改善了AP期间的生化和组织病理学变化，从而通过抗氧化和抗炎作用机制在组织学上保护了胰腺、肝脏和肺。
