Hepatoprotective effect of obeticholic acid on acetaminophen induced hepatotoxicity in mice
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https://doi.org/10.56042/ijeb.v60i12.40276Title: Hepatoprotective effect of obeticholic acid on acetaminophen induced hepatotoxicity in miceAuthors:
Awasthi, AmitVinjarapu, Prathyusha LakshmiKrishnamurthy, VenkataramanVincent, SthevaanPotturi, AnilJuluri, SureshRajagopalan, LakshmanKeywords: N-Acetyl cysteine;Liver toxicity;Silybum marianum;SilymarinIssue Date: Dec-2022Publisher: NIScPR-CSIR,IndiaAbstract: Acetaminophen (APAP) is commonly used as analgesic and antipyretic drug for relieving mild and moderate pain, but at
high doses produces hepatic necrosis. Though, Obeticholic acid (OCA) has been tested in range of diseases, its therapeutic
potential against APAP-induced hepatic injury remains to be elucidated. Thus, in this study, we investigated the preventive
effect of OCA along with N-acetylcysteine (NAC) and Silymarin (SIL) against acetaminophen-induced hepatotoxicity in
mice. SIL (100 mg/kg, po) and OCA (30 mg/kg, po) were administered continuously for six days prior to APAP
administration. After sixth dose, animas were fasted for 12 h and treated with 300 mg/kg APAP and then received SIL
(100 mg/kg, po), NAC (500 mg/kg, ip) and OCA (30 mg/kg, po) at 1 h after APAP. Mice were sacrificed 6 h after APAP
injection. Analysis of serum Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase
(ALP), liver glutathione (GSH) and histopathology were employed for assessment of hepatotoxicity. APAP group showed a
significant increase in ALT, AST, ALP and centriolobular hepatic necrosis with a significant decrease in glutathione in
comparison to control group. All these parameters were significantly improved in all the three treated groups when
compared to APAP group. In conclusion, Obeticholic acid (OCA), Silymarin (SIL) and N-acetylcysteine (NAC) are
suggested to protect against APAP-induced hepatotoxicity in mice by ameliorating liver enzymes, antioxidant effect and
decreasing liver necrosis.Page(s): 902-909ISSN: 0975-1009 (Online); 0019-5189 (Print)Appears in Collections:
IJEB Vol.60(12) [Dec 2022]Items in NOPR are protected by copyright, with all rights reserved, unless otherwise indicated.
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