Pharmacology & Toxicology Department, Faculty of Pharmacy, Ahram Canadian University, Egypt.
Pharmacology & Toxicology Department, Faculty of Pharmacy, Cairo University, Egypt.
Life Sci. 2018 Jun 1;202:78-88. doi: 10.1016/j.lfs.2018.04.002. Epub 2018 Apr 4.
This study investigated the hepatoprotective effects of both zafirlukast and vincamine and their possible role in the treatment of tamoxifen-induced liver injury in rats.
Female Wistar rats were divided into five groups (10 rats each). Groups I and II received 1% Tween 80 and served as normal and tamoxifen controls, respectively. Groups III, IV and V were treated with zafirlukast (80 mg/kg), vincamine (10 mg/kg) and a combination of zafirlukast (80 mg/kg) and vincamine (10 mg/kg), respectively for 10 successive days. Tamoxifen was given orally to all groups, except for 1st group, in the dose of 45 mg/kg for 10 days to induce liver injury. Subsequently, rats were sacrificed for biochemical, histopathological, Immunohistochemistry, PCR and western blot assessment.
Tamoxifen-induced liver injury was reflected by alterations in estimated biochemical parameters, activation of JNK/ERK pathway, increased expression of NF-κB, liver oxidative stress and inflammatory markers parallel to histopathological changes in liver tissue. Treatment of rats with zafirlukast and vincamine ameliorated tamoxifen induced hepatic cell injury via suppressing oxidative stress, inflammatory markers, caspases-3, p-JNK/p-ERK and NF-κB pathways.
Zafirlukast and vincamine may be regarded as potential therapeutic strategies with antioxidant and anti-inflammatory activities against tamoxifen-induced oxidative damage in rat liver.
本研究旨在探讨扎鲁司特和长春西汀的肝保护作用及其在治疗他莫昔芬诱导的大鼠肝损伤中的可能作用。
将雌性 Wistar 大鼠分为五组（每组 10 只）。第 I 组和第 II 组分别接受 1%吐温 80 处理，作为正常和他莫昔芬对照。第 III、IV 和 V 组分别给予扎鲁司特（80mg/kg）、长春西汀（10mg/kg）和扎鲁司特（80mg/kg）联合长春西汀（10mg/kg）连续 10 天治疗。除第 I 组外，所有组均口服给予他莫昔芬，剂量为 45mg/kg，连续 10 天诱导肝损伤。随后处死大鼠进行生化、组织病理学、免疫组织化学、PCR 和 Western blot 评估。
他莫昔芬诱导的肝损伤反映在估计的生化参数的改变、JNK/ERK 通路的激活、NF-κB 表达增加、肝氧化应激和炎症标志物的增加，以及肝组织的组织病理学变化。用扎鲁司特和长春西汀治疗大鼠可通过抑制氧化应激、炎症标志物、caspase-3、p-JNK/p-ERK 和 NF-κB 途径改善他莫昔芬诱导的肝细胞损伤。
扎鲁司特和长春西汀可能被视为具有抗氧化和抗炎活性的潜在治疗策略，可对抗他莫昔芬诱导的大鼠肝氧化损伤。
