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KMID : 0379520220380030323
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한국독성학회지
2022 Volume.38 No. 3 p.323 ~ p.330
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Adrenergic blocker terazosin potentially suppresses acetaminophen induced-acute liver injury in animal models via CYP2E1 gene
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Hashmat Zoya
Channa Iffat Saeed
Safdar Muhammad
Ozaslan Mehmet
Saeed Muhammad
Siddique Faisal
Junejo Yasmeen
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Abstract
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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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KEYWORD
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Acetaminophen, Terazosin, Alpha-adrenergic blocker, Drug-induced liver injury (DILI), CYP2E1 gene
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