Hashmat Zoya, Channa Iffat Saeed, Safdar Muhammad, Ozaslan Mehmet, Saeed Muhammad, Siddique Faisal, Junejo Yasmeen
Department of Molecular Biology, Virtual University of Pakistan, Karachi, Pakistan.
Health Education Officer, Shaheed Benazirabad, Government of Sindh, Nawabshah, Sindh, Pakistan.
Toxicol Res. 2022 Jan 11;38(3):323-330. doi: 10.1007/s43188-021-00116-y. eCollection 2022 Jul.
Drug induced liver injury (DILI) is a global issue and acetaminophen (APAP) is considered as the main cause of this. Due to increasing incidents of DILI, current study attempted to investigate an alternative but better role of terazosin (alpha-adrenergic blocker) in APAP-induced acute liver injury in an animal model using New Zealand rabbits. APAP (1 g/kg of body weight) was given to New Zealand rabbits either with or without terazosin (0.5 mg/kg) and serum was collected after 4 h. Serum alanine transaminase (ALT), alkaline phosphatase (ALP) and ferritin level were determined to analyze the liver functioning of treated rabbits. Furthermore, total cholesterol (TC), total lipids (TL), high-density lipoproteins (HDL), low-density lipoprotein (LDL) and triglycerides (TG) levels were estimated to find any change in lipid profile of the treated animals. Moreover, the urea and creatinine levels assayed the actual renal functionality. To identify any modification in gene expression, qPCR of cytochrome P2E1 (CYP2E1) was performed. Terazosin in combination with APAP enhanced liver functioning by reducing the levels of liver injury markers viz. ALP and ALT, while lipid profile was also lowered by down regulation of TC, TL, LDL and TG with enhanced HDL levels. It caused significant down regulation of expression level of CYP2E1. It is concluded that terazosin has better effects induced on the recovery of normal liver functioning, by improving the liver profile, lipid profile and renal functioning both at tissue and molecular levels.
药物性肝损伤（DILI）是一个全球性问题，对乙酰氨基酚（APAP）被认为是其主要原因。由于DILI事件不断增加，当前研究试图在使用新西兰兔的动物模型中，探究特拉唑嗪（一种α-肾上腺素能阻滞剂）在APAP诱导的急性肝损伤中替代且更好的作用。给新西兰兔给予APAP（1克/千克体重），无论是否同时给予特拉唑嗪（0.5毫克/千克），4小时后采集血清。测定血清丙氨酸转氨酶（ALT）、碱性磷酸酶（ALP）和铁蛋白水平，以分析受试兔的肝功能。此外，估计总胆固醇（TC）、总脂质（TL）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）和甘油三酯（TG）水平，以发现受试动物脂质谱的任何变化。此外，尿素和肌酐水平用于检测实际肾功能。为了确定基因表达的任何改变，进行了细胞色素P2E1（CYP2E1）的qPCR。特拉唑嗪与APAP联合使用可通过降低肝损伤标志物水平来增强肝功能，即降低ALP和ALT水平，同时通过下调TC、TL、LDL和TG水平并提高HDL水平来降低脂质谱。它导致CYP2E1表达水平显著下调。得出的结论是，特拉唑嗪通过在组织和分子水平上改善肝脏状况、脂质谱和肾功能，对正常肝功能的恢复具有更好的诱导作用。
