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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. [ABSTRACT FROM AUTHOR]

Introduction: Nickel (Ni) is widely used in industrial manufacturing and daily life due to its excellent physical and chemical properties. However, Ni has the potential to harm animals' immune system, and spleen is a typical immune organ. Therefore, it is crucial to understand the mechanism of NiCl 2 damage to the spleen. The purpose of this study is to investigate the effects of different concentrations of NiCl 2 exposure and intervening with strong antioxidants on spleen lymphocytes to better understand the damage mechanism of Ni on spleen lymphocytes., Methods: In this experiment, mice spleen lymphocytes were used as the research object. We first measured the degree of oxidative stress, inflammation, and necroptosis caused by different NiCl 2 concentrations. Subsequently, we added the powerful antioxidant N-acetyl-L-cysteine (NAC) and used hydrogen peroxide (H 2 O 2 ) as the positive control in subsequent experiments., Results: Our findings demonstrated that NiCl 2 could cause spleen lymphocytes to produce a large number of reactive oxygen species (ROS), which reduced the mRNA level of antioxidant enzyme-related genes, the changes in GSH-PX, SOD, T-AOC, and MDA, the same to the mitochondrial membrane potential. ROS caused the body to produce an inflammatory response, which was manifested by tumor necrosis factor (TNF-α) in an immunofluorescence experiment, and the mRNA level of related inflammatory genes significantly increased. In the case of caspase 8 inhibition, TNF-α could cause the occurrence of necroptosis mediated by RIP1, RIP3, and MLKL. AO/EB revealed that spleen lymphocytes exposed to NiCl 2 had significant necroptosis, and the mRNA and protein levels of RIP1, RIP3, and MLKL increased significantly. Moreover, the findings demonstrated that NAC acted as an antioxidant to reduce oxidative stress, inflammation, and necroptosis caused by NiCl 2 exposure., Discussion: Our findings showed that NiCl 2 could cause oxidative stress, inflammation, and necroptosis in mice spleen lymphocytes, which could be mitigated in part by NAC. The study provides a point of reference for understanding the toxicological effect of NiCl 2 . The study suggests that NAC may be useful in reducing the toxicological effect of NiCl 2 on the immune system. The research may contribute to the development of effective measures to prevent and mitigate the toxicological effects of NiCl 2 on the immune system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Xu, Ma, Shi, Liu, Song, Fang, Liu, Qiao, Cai and Zhang.)