We are increasingly exposed to endocrine disruptors (EDCs) that interfere with the normal functioning of our hormones. Bisphenol A (BPA) and phthalates, which are widely used in consumer products including plastics, aluminum cans, pharmaceuticals and cosmetics, are well-known endocrine disruptors.
Since BPA and phthalates are structurally similar to steroid hormones that regulate chemical signaling in the body, they are able to manipulate and disrupt hormone functions. The liver, seat of energy metabolism and detoxification of xenobiotics, is the main target of these endocrine disruptors. The liver converts these endocrine disruptors into non-toxic, water-soluble metabolites for excretion via urine. However, this biotransformation process generates reactive intermediates that accumulate in the liver, causing cell death and organ failure.
Studies involving animal models and human urine samples have confirmed the positive correlation between exposure to individual endocrine disruptors and abnormal liver function. However, they do not account for real-world scenarios where uncontrolled multichemical exposure occurs simultaneously.
To address this issue, Prof. Myung-Geol Pang and colleagues at Chung-Ang University, Korea, studied the effects of combined exposure to BPA and phthalates on liver function and metabolic homeostasis in mouse models. Elaborating on the design of their study, Professor Pang observes: “We determined the combined effects of several endocrine disruptors using a concept of simulation of real risk. Their study was posted online May 26, 2022 and will be published August 15, 2022 in Volume 436 of the Journal of Hazardous Materials.
Professor Pang and his team evaluated the effects of BPA and an EDC mixture consisting of BPA and seven phthalate compounds on male mice. They observed that neither BPA alone nor the EDC mixture affected liver function at the permissible human daily exposure (ED) limits set by the Korean Ministry of Food and Drug Safety. However, significant changes in the liver were observed when the dose of the EDC mixture was increased to 25, 250 and 2500 times the DE limit, including an increase in overall liver weight. The study recorded an accumulation of lipids, triglycerides and cholesterol – forms in which fat is stored in the body – in the liver, in addition to elevated blood sugar with these high levels of EDC exposure. Scientists hypothesized that EDCs induce the expression of key genes involved in glucose production and transport pathways, which ultimately impact liver health.
Since exposure to EDCs is known to impair liver enzymes, the team looked at levels of blood serum components that indicate liver damage. Increased levels of the enzyme aminotransferase have been observed upon exposure to EDC blend levels greater than 25 times the recommended DE level, indicating liver damage. In addition, a ratio of aspartate and alanine aminotransferase greater than 1 was also observed, indicating a higher risk of non-alcoholic fatty liver disease and the progression of liver fibrosis due to increased deposition of fatty acids. collagen. Additionally, anti-inflammatory cytokines were found to be aggravated in mice exposed to EDC, resulting in steatohepatitis, a condition in which excess fat accumulates in the liver, causing cell death and progression. hepatic fibrosis. It should be noted here that the mammalian immune system secretes pro-inflammatory cytokines in response to dangerous chemicals, such as endocrine disruptors, or infections, thereby contributing to liver inflammation.
Interestingly, markers of oxidative stress and cell death by apoptosis were also observed to be abundant in mice exposed to EDC. Scientists have attributed this to the reduced antioxidant capacity of the liver damaged by endocrine disruptors.
This study is important because it assesses the impact of toxic chemicals in a real-world scenario, which is essential to highlighting and defining their permissible levels in consumer products. “Combined exposure to EDCs can increase overall EDC intake, leading to significant health consequences,” says Professor Pang. What implications might their findings have? “Our study attempted to change the conventional toxicological approach and we hope it will have a huge impact on regulatory and public health perspectives,” says Professor Pang.
Authors: Md Saidur Rahman, Won-Ki Pang, Shehreen Amjad, Do-Yeal Ryu, Elikanah Olusayo Adegoke, Yoo-Jin Park, Myung-Geol Pang
Affiliations: Department of Animal Science and Technology and BET Research Institute, Chung-Ang University, Anseong, Gyeonggi-do 17546, Republic of Korea
About Chung-Ang University
Chung-Ang University (CAU) is a private comprehensive research university located in Seoul and Anseong, South Korea, and it is widely regarded as one of the best universities in Korea. In particular, CAU’s cultural and artistic programs are considered the best in Korea. It was established in 1916. The birth of many disciplines, namely pharmacy, business, media, social welfare, arts, etc. started at CAU in Korea. Its new vision to complete its 100 years is to become “The world leader in creation”. CAU offers undergraduate, postgraduate, and doctoral programs in law, management, and medicine; it has 16 undergraduate and graduate schools each. Recently, outstanding research achievements in the field of biotechnology and natural resources are attracting global attention.
About Professor Myung-Geol Pang
Professor Myung-Geol Pang currently works in the Department of Animal Science and Technology in addition to serving as Director of the BET Research Institute at Chung-Ang University in South Korea. He holds a doctorate. in Cellular Endocrinology and Reproductive Biology from Eastern Virginia Medical School, USA. He is a member of the prestigious Korea Academy of Science and Technology and previously held notable research positions at Seoul National University, Korea Advanced Institute of Science and Technology during his career. Professor Pang and his team have received numerous accolades for their work on environmental health and male fertility.