Di-(2-ethylhexyl) phthalate-induced hepatotoxicity exacerbated type 2 diabetes mellitus (T2DM) in female pubertal T2DM mice.

Abstract

Di-(2-ethylhexyl) phthalate (DEHP), one of the most common plasticizers, is closely associated with a high prevalence of pubertal type 2 diabetes mellitus (T2DM). Numerous studies have indicated that DEHP-induced metabolic toxicity exhibits sex differences. In this study, the sex differences in the effect of DEHP on pubertal T2DM (P-T2DM) mice, the susceptibility of female P-T2DM mice to DEHP-induced metabolic toxicity, and the underlying mechanisms were investigated. DEHP exposure exacerbated metabolic disorders in female P-T2DM mice. Factorial analysis showed that female P-T2DM mice were more sensitive to DEHP exposure than female normal mice and male P-T2DM mice. It was determined by integrated biomarker response results that female P-T2DM mice had higher risks of developing T2DM, metabolic disorders, cardiovascular events and hepatotoxicity than male P-T2DM mice. Moreover, hepatic transcriptome analysis emphasized the effects of DEHP on the expression of oxidative injury- and metabolic function-related genes. Western blotting indicated that DEHP activated Jun-N-terminal kinase (JNK) and impaired insulin sensitivity in the liver, which were the main causes of DEHP-exacerbated metabolic abnormalities in P-T2DM mice. Our study revealed that compared with normal mice and male P-T2DM mice, female P-T2DM mice tend to suffer from increased DEHP-induced metabolic toxicity, which was primarily attributed to hepatotoxicity.

• Authors: Yangyang Ding, Tong Xu, Guanghua Mao, Yao Chen, Xuchun Qiu, Liuqing Yang, Ting Zhao, Xiaoxiao Xu, Weiwei Feng, Xiangyang Wu
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 149 Pg. 112003 (Mar 2021) ISSN: 1873-6351 [Electronic] England
• PMID: 33484791 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Environmental Pollutants
• Diethylhexyl Phthalate

Topics

• Animals
• Chemical and Drug Induced Liver Injury (pathology)
• Diabetes Mellitus, Experimental
• Diabetes Mellitus, Type 2 (pathology)
• Diethylhexyl Phthalate (toxicity)
• Environmental Pollutants (toxicity)
• Female
• Male
• Mice
• Mice, Inbred ICR
• Principal Component Analysis