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Hepatoprotective effect of obeticholic acid on acetaminophen induced hepatotoxicity in mice

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Title Statement Hepatoprotective effect of obeticholic acid on acetaminophen induced hepatotoxicity in mice
 
Added Entry - Uncontrolled Name Awasthi, Amit ; GVK Biosciences Pvt Ltd
Vinjarapu, Prathyusha Lakshmi Vinjarapu1 Lakshmi; GVK Biosciences, Hyderabad
Krishnamurthy, Venkataraman ; GVK Biosciences, Hyderabad
Vincent, Sthevaan ; GVK Biosciences, Hyderabad
Potturi, Anil ; GVK Biosciences, Hyderabad
Juluri, Suresh ; GVK Biosciences, Hyderabad
Rajagopalan, Lakshman ; GVK Biosciences, Hyderaba
 
Uncontrolled Index Term N-Acetyl cysteine; Liver toxicity; Silybum marianum; Silymarin
 
Summary, etc. 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.
 
Publication, Distribution, Etc. Indian Journal of Experimental Biology (IJEB)
2022-12-01 10:08:04
 
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http://op.niscair.res.in/index.php/IJEB/article/view/40276
 
Data Source Entry Indian Journal of Experimental Biology (IJEB); ##issue.vol## 60, ##issue.no## 12 (2022): IJEB [DECEMBER 2022]
 
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