Zoology Department, Faculty of Science, Cairo University, 12613, Giza, Egypt.
Toxicol Lett. 2019 Feb;301:73-78. doi: 10.1016/j.toxlet.2018.11.006. Epub 2018 Nov 17.
Drug-induced hepatotoxicity is an extremely widespread condition and is responsible for a variety of pathological effects on the liver. It was reported that hepatotoxicity induced by angiotensin converting enzyme inhibitors (ACEIs) is cholestasis mediated hepatitis. Bradykinin-potentiating factor (BPF) is one of the natural ACEIs. Although prolonged treatment with ACEIs provides protection against liver injury, the effect of short-term treatment with ACEIs has not been fully elucidated before. Thereby, the present study sought to determine if transient ACE inhibition may exacerbate the hepatotoxicity caused by bile duct ligation (BDL) in rats.
Twenty one Wistar rats were divided into 3 groups: Sham-operated group, bile duct ligated (BDL) rats, and BDL rats treated for short-term with BPF (1 μg/kg body weight) day after day for one week and biochemical parameters were measured. Also, we assessed expression level of ACE1 and detection of hepatotoxicity in the liver tissues of different groups.
There was a significant increase in liver enzymes, bilirubin levels, and oxidative stress in the BDL group after treatment with BPF as compared to BDL group. We found overexpression of ACE1 gene in BDL group compared to BPF and Sham-operated control group. Histopathological examination of liver treated with BPF showed severe degeneration hepatic architecture and hepatocytes as compared to BDL group. Collagen deposition increased after BPF treatment as compared to BDL groups.
The present investigation suggests and recommends that short- term ACE inhibition pathway potentiates liver fibrosis during cholestasis disease.
药物性肝毒性是一种极其普遍的病症，可导致肝脏发生多种病理变化。有报道称，血管紧张素转换酶抑制剂（ACEIs）引起的肝毒性是胆汁淤积性肝炎。缓激肽增强因子（BPF）是天然 ACEIs 之一。尽管长期使用 ACEIs 可提供肝损伤保护，但 ACEIs 的短期治疗效果尚未完全阐明。因此，本研究旨在确定短暂的 ACE 抑制是否会加重胆管结扎（BDL）大鼠的肝毒性。
将 21 只 Wistar 大鼠分为 3 组：假手术组、胆管结扎（BDL）大鼠组和 BDL 大鼠组，BDL 大鼠组每日给予 BPF（1μg/kg 体重）治疗 1 周，并测量生化参数。同时，我们评估了不同组肝脏组织中 ACE1 的表达水平和肝毒性。
与 BDL 组相比，BPF 处理后的 BDL 组的肝酶、胆红素水平和氧化应激显著增加。与 BPF 和假手术对照组相比，BDL 组 ACE1 基因表达过度。与 BDL 组相比，BPF 处理后的肝组织病理检查显示肝组织结构严重变性和肝细胞严重变性。与 BDL 组相比，BPF 处理后胶原沉积增加。
本研究表明，短期 ACE 抑制途径可增强胆汁淤积性疾病中的肝纤维化。
