Grape seed extract proanthocyanidin antagonizes aristolochic acid I-induced liver injury in rats by activating PI3K-AKT pathway

Abstract

Aristolochic acid is internationally recognized as a carcinogen. It has been shown that the main toxic mechanism of aristolochic acid on the liver and kidney is the induction of ROS-induced oxidative stress damage. To investigate whether proanthocyanidins (GSPE), a natural antioxidant product from grape seed extract, could antagonize AA-I-induced liver injury. Thirty-two SD rats were selected and divided into aristolochic acid exposure group (AA-I), normal control group, GSPE group and GSPE intervention group. The protective effects of GSPE on AA-I liver injury were evaluated by examining the body weight, liver index, liver function and liver pathological sections of rats. The results of body weight, liver index, liver function and liver pathological sections of rats showed that GSPE had antagonistic effects on AA-I-induced liver injury. antioxidant enzyme activity in the GSPE intervention group was significantly higher than that in the aristolochic acid group, apoptotic cells were significantly lower than that in the aristolochic acid group, protein and mRNA expression of PI3K-AKT and BCL-2 were significantly higher than that in the aristolochic acid group, BAX, The protein and mRNA expression of BAX, CASPAES-3, CASPAES-9 were significantly lower than those of the aristolochic acid group. GSPE can antagonize aristolochic acid-induced hepatotoxicity, and its mechanism of action is to antagonize aristolochic acid I-induced liver injury by inhibiting PI3K-AKT pathway-mediated hepatocyte apoptosis.

Graphical Abstract

Keywords:

• Aristolochic acid
• liver
• toxicity
• oxidative stress
• grape seed proanthocyanidin extract

Ethics statement

All of the procedures used in this study were approved by the Institutional Animal Care and Use Committee of Northeast Agricultural University.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Datasets analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

Thanks to the National Natural Science Foundation of China for the financial support for the experiment, the National Natural Science Foundation of China Project Approval Number: 32072909.