Biswas Ayan, Santra Suman, Bishnu Debasree, Dhali Gopal Krishna, Chowdhury Abhijit, Santra Amal
Centre for Liver Research, School of Digestive & Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India.
Indiana University School of Medicine, Indianapolis, USA.
Int J Hepatol. 2020 Apr 23;2020:6987295. doi: 10.1155/2020/6987295. eCollection 2020.
A combined dose of INH (50 mg) and RMP (100 mg) per kg body weight per day was administered to mice by oral gavage, 6 days a week, for 4 to 24 weeks for the assessment of liver injury, oxidative stress, and development of hepatic fibrosis, including demonstration of changes in key fibrogenesis linked pathways and mediators.
Progressive increase in markers of hepatic stellate cell (HSC) activation associated with changes in matrix turnover was observed between 12 and 24 weeks of INH-RMP treatment along with the elevation of liver collagen content and significant periportal fibrosis. These were associated with concurrent apoptosis of the hepatocytes, increase in hepatic cytochrome P450 2E1 (CYP2E1), NADPH oxidase (NOX) activity, and development of hepatic oxidative stress.
INH-RMP can activate HSC through generation of NOX-mediated oxidative stress, leading to the development of liver fibrosis.
通过口服灌胃给予小鼠每天每千克体重联合剂量的异烟肼（50毫克）和利福平（100毫克），每周6天，持续4至24周，以评估肝损伤、氧化应激和肝纤维化的发展，包括关键纤维化相关途径和介质变化的证明。
在异烟肼-利福平治疗的12至24周期间，观察到与基质周转变化相关的肝星状细胞（HSC）活化标志物逐渐增加，同时肝胶原含量升高和明显的门静脉周围纤维化。这些与肝细胞的同时凋亡、肝细胞色素P450 2E1（CYP2E1）增加、NADPH氧化酶（NOX）活性以及肝氧化应激的发展有关。
异烟肼-利福平可通过产生NOX介导的氧化应激激活HSC，导致肝纤维化的发展。
