Luteolin-mediated PI3K/AKT/Nrf2 signaling pathway ameliorates inorganic mercury-induced cardiac injury

• Published in: Ecotoxicology and environmental safety 2018-10, Vol.161, p.655-661
• Main Authors: Baiyun, Ruiqi, Li, Siyu, Liu, Biying, Lu, Jingjing, Lv, Yueying, Xu, Jianwen, Wu, Jiahui, Li, Jiayi, Lv, Zhanjun, Zhang, Zhigang
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Cardiac damage; Flavonoid compound; Heart - drug effects; HgCl2; Luteolin; Luteolin - pharmacology; Male; Mercuric Chloride - toxicity; Myocardium - metabolism; Myocardium - pathology; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; Oxidative Stress - drug effects; Phosphatidylinositol 3-Kinase - metabolism; PI3K/AKT/Nrf2; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Wistar; Signal Transduction - drug effects
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2018.06.046

Inorganic mercury is a toxic metal of worldwide concern, and causes serious cardiac injury. However, effective treatment for cardiac injury induced by mercuric chloride (HgCl2) has not been fully identified. Luteolin (Lut) is a novel natural antioxidant. This study aimed to investigate the role of Lut on HgCl2-induced cardiac injury. Male Wistar rats were randomly assigned to 4 groups, control, Lut (80 mg/kg intragastrically), HgCl2 (80 mg/L, in drinking water), and HgCl2 + Lut groups. The results indicated that Lut significantly ameliorated cardiac histopathological damage, oxidative stress, and apoptosis induced by HgCl2 in the rat heart. Furthermore, Lut evidently increased levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and nuclear factor-erythroid-2-related factor 2 (Nrf2) and its downstream proteins, and inhibited NF-κB activation in the heart of rats treated by HgCl2. Taken together, our findings suggest that activating PI3K/AKT/Nrf2 signaling pathway is involved in the protective effect of Lut against HgCl2-induced cardiac damage. Synopsis Potential mechanism of luteolin in HgCl2-induced heart injury. Luteolin protected against HgCl2-induced heart injury by alleviating oxidative stress and apoptosis through increased levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and nuclear factor-erythroid-2-related factor 2 (Nrf2) and its downstream proteins, and inhibited NF-κB activation. [Display omitted] •Luteolin (Lut) ameliorated HgCl2-induced cardiac apoptosis and oxidative stress.•Lut reduced the mercuric accumulation in the blood and heart.•Lut attenuated HgCl2-induced cardiac injury by activating PI3K/AKT/Nrf2 signaling pathway.