Salimi Ahmad, Khezri Saleh, Amani Mojtaba, Badrinezhad Niknaz, Hosseiny Sahar, Saadati Reza
Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Mol Cell Biochem. 2025 Jan 4. doi: 10.1007/s11010-024-05180-0.
Chronic/heavy exposure with ethanol is associated with risk of type 2 diabetes, due to β-cells dysfunction. It has been reported that ethanol can induce oxidative stress directly or indirectly by involvement of mitochondria. We aimed to explore the protective effects of the crocin/gallic acid/L-alliin as natural antioxidants separately on ethanol-induced mitochondrial damage. Intact mitochondria are isolated from pancreas by differential centrifugation and directly treated with toxic concentrations of ethanol (8% v/v) in the presence of different concentrations crocin/gallic acid/L-alliin (100, 500, and 1000 µM). Biomarkers of mitochondrial toxicity including the succinate dehydrogenases (SDH) activity, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial swelling, lipid peroxidation, and glutathione content were assessed. The results showed that 8% v/v ethanol-treated rat pancreas-isolated mitochondria for 1 h resulted in a significant decrease of SDH activity to 81.34 ± 3.48%, a significant increase of ROS formation, MDA content, mitochondrial swelling, and collapse of MMP. Among three tested natural compounds, treatment with crocin and gallic acid significantly reversed the changes of the above indicators and resulted in the increase of SDH activity, improvement of MMP collapse and mitochondrial swelling, and reduction of ROS formation and oxidative stress in pancreas-isolated mitochondria. This study demonstrated that crocin and gallic acid had direct protective effects on the mitochondrial damages induced by ethanol in pancreas-isolated mitochondria, and these natural compounds could be developed as mitochondrial protective agents in the prevention of pancreatic β-cells and diabetogenic effect of ethanol.
长期/大量接触乙醇与2型糖尿病风险相关，这是由于β细胞功能障碍所致。据报道，乙醇可通过线粒体的参与直接或间接诱导氧化应激。我们旨在分别探讨藏红花素/没食子酸/L-蒜氨酸作为天然抗氧化剂对乙醇诱导的线粒体损伤的保护作用。通过差速离心从胰腺中分离出完整的线粒体，并在不同浓度的藏红花素/没食子酸/L-蒜氨酸（100、500和1000 μM）存在的情况下，用有毒浓度的乙醇（8% v/v）直接处理。评估线粒体毒性的生物标志物，包括琥珀酸脱氢酶（SDH）活性、活性氧（ROS）、线粒体膜电位（MMP）、线粒体肿胀、脂质过氧化和谷胱甘肽含量。结果表明，用8% v/v乙醇处理大鼠胰腺分离的线粒体1小时，导致SDH活性显著降低至81.34±3.48%，ROS形成、丙二醛（MDA）含量、线粒体肿胀显著增加，MMP崩溃。在三种测试的天然化合物中，藏红花素和没食子酸处理显著逆转了上述指标的变化，导致SDH活性增加，MMP崩溃和线粒体肿胀得到改善，胰腺分离线粒体中ROS形成和氧化应激降低。本研究表明，藏红花素和没食子酸对胰腺分离线粒体中乙醇诱导的线粒体损伤具有直接保护作用，这些天然化合物可开发为线粒体保护剂，用于预防胰腺β细胞和乙醇的致糖尿病作用。
