Cr (VI) induces abnormalities in glucose and lipid metabolism through ROS/Nrf2 signaling

Ecotoxicology and Environmental Safety

Wanwei Li¹  Lanhua Li²  Xiaoli Yu³  Xiaohong Li⁴  Shengwen He⁴  Jian Zhou⁴  Yumei Liu⁵ 

[1] Department of Environmental Hygiene, School of Public Health, Weifang Medical College, Weifang, China;Department of Epidemiology, School of Public Health, Weifang Medical College, Weifang, China;Department of Health Inspection and Quarantine, School of Public Health, Weifang Medical College, Weifang, China;Department of Nutrition and Food Hygiene, School of Public Health, Weifang Medical College, Weifang, China;Public Health Demonstration Center, School of Public Health, Weifang Medical College, Weifang, China;

关键词: Cr (VI);    Glucose and lipid metabolic disorder;    ROS;    Nrf2/HO-1;    NAC;   

DOI  :  

来源: DOAJ

【 摘 要 】

The hexavalent form of chromium, Cr (VI), has been associated with various diseases in humans. In this study, we examined the mechanisms underlying the effect of Cr (VI) on glucose and lipid metabolism in vivo and in vitro. We found that Cr (VI) induced abnormal liver function, increased fasting blood glucose (FBG), as well as glucose and insulin intolerance in mice. Furthermore, Cr (VI) decreased glucose-6-phosphate (G6P) level and glucose transporter-2 (GLUT2) expression, increased the levels of triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), reduced high-density lipoprotein-cholesterol (HDL-C), and increased sterol regulatory element-binding proteins 1 (SREBP1) and fat synthase (FAS) in vitro and in vivo. Moreover, Cr (VI) promoted intracellular ROS production in vitro, and induced reduction of antioxidant enzyme level and Nrf2/HO-1 expression in vitro and in vivo. Also, N-acetyl cysteine (NAC, effective antioxidant and free radical scavenger) pretreatment inhibited the production of intracellular ROS, significantly suppressed Cr (VI)-induced oxidative stress, lipid accumulation, decreased G6P and GLUT2, and improved impaired glucose tolerance and glucose and insulin intolerance caused by Cr (VI) in mice. Dh404 activated expression of Nrf2 decreased ROS level, increased HO-1 expression, ameliorated activity of the antioxidant enzyme, inhibited Cr (VI) increase of SREBP1, FAS level, and reduction of G6P and GLUT2. To sum up, these data suggest that dysregulation of ROS/Nrf2/HO-1 has an important role in Cr (VI)-induced glucose/lipid metabolic disorder.

【 授权许可】

Unknown