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Liver is a principal organ that preserves the homeostasis of human body and performs many other functions including; detoxification of drugs, storing glycogen, regulating cholesterol and metabolism of urea. Liver injury induced by drugs is still a critical obstacle in the successful development of medicines. Acetaminophen (APAP) is an extensively consumed pain killer and is also the main cause of Drug Induced Liver Injury (DILI). An established biomarker for analyzing liver injury at molecular level is Cytochrome-P450 2E1 (CYP2E1) enzyme, mostly associated with the acetaminophen hepatotoxicity. Thus, a safer more reliable and economical way to deal with DILI is to determine an alternative use of the approved drugs. Binding of adrenergic ligands with their particular receptors is prevented by alpha-adrenergic blockers and is used in treating benign prostatic hyperplasia, cardiovascular disorders and erectile dysfunction. In this current proposal we have investigated whether terazosin (TER), an alpha adrenergic blocker, is effective as a hepatoprotective agent in an acetaminophen induced acute liver injury induced animal model. White New Zealand rabbits were used as animal models and were given an oral dose of acetaminophen to induce acute liver injury. It was observed that the Adenosine triphosphate (ALT) and Alkaline phosphatase (ALP) levels were much reduced by TER. ALT results showed statistical significance when compared with APAP alone. The serum ferritin level result was found to be decreased following the APAP intake. Lipid profile was much improved by TER as it decreased the level of Triglycerides (TG), Total Cholesterol (TC), Total Lipids (TL) and Low Density Lipoproteins (LDL) and increased the level of High Density Lipoproteins (HDL). TG level was statistically significant when comparing CON with both APAP and TER. Urea and creatinine level was also reduced indicating that TER acts as renal efficient agent. As CYP2E1 is upregulated during liver injury, it was observed that TER downregulated the expression level of CYP2E1. Hence, it can be stated that TER is not only safer for arterial hypertension but it is safe for human consumption. TER showed prevention of acute liver injury that was caused by acetaminophen, thus further studies can strengthen its alternative use in hepatoprotection.
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