School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, China.
School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu, China.
Toxicol Lett. 2022 Mar 1;356:41-53. doi: 10.1016/j.toxlet.2021.12.004. Epub 2021 Dec 8.
Diabetes mellitus is a common endocrine metabolic disorder, and previous studies have shown that diabetics are more sensitive to the toxic environmental contaminants. Acrylamide (ACR) is both an industrially multipurpose compound and a common endogenous food contaminant to which people are frequently exposed and at high risk. However, the toxicity of ACR on diabetes hasn't attracted much attention. In this study, both healthy mice and diabetic mice received ACR administration orally to investigate the ACR-induced metabolic toxicity, mechanism and susceptibility to ACR toxicity in adult diabetic male mice. The results showed that ACR significantly increased FBG level and decreased bodyweight, serum lipid and liver lipid biomarkers (TC, TG, LDL-C, HDL-C) levels as well as expression of lipid and glucose metabolism-related genes in diabetic mice, indicating that ACR can exacerbate metabolic disorders of glucose and lipid in diabetic male mice. Moreover, ACR exposure significantly increased levels of MDA and COX-2), decreased GSH level and antioxidant enzyme activity (SOD, GSH-PX and CAT) by downregulating expression of Nrf2 and Keap1 in diabetic mice. Factorial analysis showed ACR had a more significant disturbance in diabetic mice compared with healthy mice. Our results indicated that ACR exposure can cause oxidative stress and inflammatory damage, which can exacerbate abnormal glucose and lipid metabolism. This work helps to elucidate the effects and underlying mechanisms of ACR-induced metabolic toxicity in adults with diabetes.
糖尿病是一种常见的内分泌代谢紊乱疾病，先前的研究表明，糖尿病患者对有毒环境污染物更敏感。丙烯酰胺（ACR）既是一种工业多用化合物，也是一种常见的内源性食物污染物，人们经常接触并处于高风险之中。然而，丙烯酰胺对糖尿病的毒性尚未引起太多关注。在这项研究中，健康小鼠和糖尿病小鼠均通过口服给予丙烯酰胺，以研究丙烯酰胺诱导的成年雄性糖尿病小鼠的代谢毒性、机制和易感性。结果表明，丙烯酰胺显著增加了糖尿病小鼠的 FBG 水平，降低了体重、血清脂质和肝脂质生物标志物（TC、TG、LDL-C、HDL-C）水平以及脂质和糖代谢相关基因的表达，表明丙烯酰胺可加重糖尿病雄性小鼠的糖脂代谢紊乱。此外，丙烯酰胺暴露通过下调糖尿病小鼠中 Nrf2 和 Keap1 的表达，显著增加 MDA 和 COX-2 的水平，降低 GSH 水平和抗氧化酶活性（SOD、GSH-PX 和 CAT）。析因分析表明，与健康小鼠相比，丙烯酰胺在糖尿病小鼠中具有更显著的干扰作用。我们的结果表明，丙烯酰胺暴露会导致氧化应激和炎症损伤，从而加重异常的糖脂代谢。这项工作有助于阐明丙烯酰胺诱导的成年糖尿病患者代谢毒性的作用和潜在机制。
