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Adrenergic blocker terazosin potentially suppresses acetaminophen induced-acute liver injury in animal models via CYP2E1 gene

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Abstract

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.

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Funding

The study was supported by departmental research grant.

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Authors and Affiliations

  1. Department of Molecular Biology, Virtual University of Pakistan, Karachi, Pakistan

    Zoya Hashmat & Iffat Saeed Channa

  2. Division of Molecular Biology and Genetics, Deparment of Biology, Gaziantep University, Gaziantep, 27000, Turkey

    Muhammad Safdar & Mehmet Ozaslan

  3. Cholistan University of Veterinary and Animal Sciences, Bahawalpur, 63100, Pakistan

    Muhammad Safdar, Muhammad Saeed & Yasmeen Junejo

  4. Derpartment of Microbiology, Cholistan University of Veterinary & Animal Sciences, Bahawalpur, 63100, Pakistan

    Faisal Siddique

  5. Health Education Officer, Shaheed Benazirabad, Government of Sindh, Nawabshah, Sindh, Pakistan

    Iffat Saeed Channa

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  1. Zoya Hashmat
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Correspondence to Muhammad Safdar.

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Hashmat, Z., Channa, I.S., Safdar, M. et al. Adrenergic blocker terazosin potentially suppresses acetaminophen induced-acute liver injury in animal models via CYP2E1 gene. Toxicol Res. 38, 323–330 (2022). https://doi.org/10.1007/s43188-021-00116-y

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  • DOI: https://doi.org/10.1007/s43188-021-00116-y

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