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Hepatoprotective effect of obeticholic acid on acetaminophen induced hepatotoxicity in mice

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Title Hepatoprotective effect of obeticholic acid on acetaminophen induced hepatotoxicity in mice
 
Creator Awasthi, Amit
Vinjarapu, Prathyusha Lakshmi
Krishnamurthy, Venkataraman
Vincent, Sthevaan
Potturi, Anil
Juluri, Suresh
Rajagopalan, Lakshman
 
Subject N-Acetyl cysteine
Liver toxicity
Silybum marianum
Silymarin
 
Description 902-909
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.
 
Date 2022-12-02T06:20:53Z
2022-12-02T06:20:53Z
2022-12
 
Type Article
 
Identifier 0975-1009 (Online); 0019-5189 (Print)
http://nopr.niscpr.res.in/handle/123456789/60992
https://doi.org/10.56042/ijeb.v60i12.40276
 
Language en
en
 
Publisher NIScPR-CSIR,India
 
Source IJEB Vol.60(12) [Dec 2022]