Lupeol prevents acetaminophen-induced in vivo hepatotoxicity by altering the Bax/Bcl-2 and oxidative stress-mediated mitochondrial signaling cascade

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• 作者：Archana Kumari ; Poonam Kakkar ; ^{poonam_kakkar@yahoo.com}
• 关键词：Acetaminophen ; Oxidative stress ; Mitochondrial depolarization ; Hepatotoxicity ; Lupeol
• 刊名：Life Sciences
• 出版年：2012
• 期刊代码：62_00243205
• 类别：imm
• 出版时间：20 April, 2012
• 卷：90
• 期：15-16
• 页码：561-570
• 文件大小：1060 K

摘要

Aims

Lupeol, a triterpene, possesses numerous pharmacological activities, including anti-malarial, anti-arthritic and anti-carcinogenic properties. The present study was conducted to explore the hepatoprotective potential of lupeol against acetaminophen (AAP)-induced hepatotoxicity in Wistar rats.

Main methods

Rats were given a prophylactic treatment of lupeol (150 mg/kg body weight, p.o., for 30 consecutive days) with a co-administration of AAP (1 g/kg body weight). The modulatory effects of lupeol on AAP-induced hepatotoxicity were investigated by assaying oxidative stress biomarkers, serum liver toxicity markers, pro/anti apoptotic proteins, DNA fragmentation and by the histopathological examination of the liver.

Key findings

Lupeol significantly prevented hepatic damage as evident from the histopathological studies and significant decline in serum trans-aminases. The alterations in cellular redox status (p < 0.01) and antioxidant enzyme activities together with the enhanced lipid peroxidation and protein carbonyl levels were also observed in the AAP-treated rats. In addition, significant ROS generation and mitochondrial depolarization were observed in this group. Co-administration of lupeol significantly decreased the level of serum transaminases, MDA and protein carbonyl content. It also prevented ROS generation and mitochondrial depolarization. Furthermore, lupeol enhanced the mitochondrial antioxidant and redox status and inhibited DNA damage and cell death by preventing the downregulation of Bcl-2, upregulation of Bax, release of cytochrome c and the activation of caspase 9/3.

Significance

The conclusion of this study is that lupeol when co-administered with AAP effectively reduces oxidative stress and prevents AAP-induced hepatotoxicity by inhibiting critical control points of apoptosis.