Graduate School of Biomedical and Health Sciences, Hiroshima University, 734-8553, Japan.
Graduate School of Biomedical and Health Sciences, Hiroshima University, 734-8553, Japan.
Toxicol Appl Pharmacol. 2019 May 1;370:133-144. doi: 10.1016/j.taap.2019.03.010. Epub 2019 Mar 14.
Liver resection is performed to remove tumors in patients with liver cancer, but the procedure's suitability depends on the regenerative ability of the liver. It is important to consider the effects of exogenous factors, such as diets, on liver regeneration for the recovery of function. The evaluation of drug metabolism during liver regeneration is also necessary because liver dysfunction is generally observed after the operation. Here, we investigated the influence of a purified diet (AIN-93G) on liver regeneration and changes in the mRNA expression of several cytochrome P450 (CYP) isoforms in the liver and small intestine using a two-thirds partial hepatectomy (PH) mouse model fed with a standard diet (MF) and a purified diet. Liver regeneration was significantly delayed in the purified diet group relative to that in the standard diet group. The liver Cyp2c55 and Cyp3a11 expression was increased at 3 day after PH especially in the purified diet group. Bile acid may partly cause the differences in liver regeneration and CYP expression between two types of diets. On the other hand, Cyp3a13 expression in the small intestine was transiently increased at day 1 after PH in both diet groups. The findings suggest that compensatory induction of the CYP expression occurred in the small intestine after attenuation of drug metabolism potential in the liver. The present results highlight the importance of the relationship between liver regeneration, drug metabolism, and exogenous factors for the effective treatment, including surgery and medication, in patients after liver resection or transplantation.
肝切除术用于切除肝癌患者的肿瘤,但该手术的适用性取决于肝脏的再生能力。考虑外源性因素(如饮食)对肝脏再生和功能恢复的影响非常重要。由于手术后通常会出现肝功能障碍,因此还需要评估药物代谢在肝再生期间的变化。在这里,我们使用标准饮食(MF)和纯化饮食喂养的二分之三部分肝切除术(PH)小鼠模型,研究了纯化饮食(AIN-93G)对肝再生和肝脏及小肠中几种细胞色素 P450(CYP)同工型的 mRNA 表达变化的影响。与标准饮食组相比,纯化饮食组的肝再生明显延迟。PH 后 3 天,肝 Cyp2c55 和 Cyp3a11 的表达尤其在纯化饮食组中增加。胆汁酸可能部分导致两种饮食之间肝再生和 CYP 表达的差异。另一方面,两种饮食组的小肠 Cyp3a13 表达在 PH 后第 1 天短暂增加。这些发现表明,在肝脏药物代谢能力减弱后,小肠中 CYP 表达发生了代偿性诱导。这些结果强调了肝再生、药物代谢和外源性因素之间的关系对于肝切除或移植后患者的有效治疗(包括手术和药物治疗)的重要性。