Chung-Ang University Study Reports Hepatic Toxicity from Endocrine Disrupting Chemical Mixtures
Scientists evaluate the impact of toxic, endocrine-disrupting chemicals like bisphenol A and phthalates on liver function and metabolic homeostasis
Humans are constantly exposed to harmful endocrine-disrupting chemicals (EDCs), including phthalates and bisphenol A (BPA) through cosmetics and plastics. Now scientists from South Korea have demonstrated that EDCs, particularly in mixture forms, may damage the mammalian liver and cause metabolic diseases. While mice exposed to these compounds at permissible human exposure limits suffered minimal effects, their liver function was greatly affected by higher levels of EDCs because of disruptions in genetic and non-genetic pathways.
We are increasingly being exposed to endocrine-disrupting chemicals (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 EDCs.
Since both BPA and phthalates are structurally similar to steroid hormones that regulate chemical signaling in the body, they are capable of manipulating and disrupting hormonal functions. The liver, the seat of energy metabolism and xenobiotic detoxification, is the main target of these EDCs. The liver converts these EDCs 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 EDCs and abnormal liver function. However, they fail to consider real-life scenarios where uncontrolled multi-chemical exposure occurs simultaneously.
To address this issue, Professor Myung-Geol Pang and his colleagues from Chung-Ang University, Korea investigated the effects of the combined exposure to BPA and phthalates on liver function and metabolic homeostasis in mice models. Elaborating on their study’s design, Prof. Pang observes, “We determined the combined effects of multiple EDCs using a real-life risk simulation concept.” Their study was made available online on May 26, 2022 and is to be published on August 15, 2022, in volume 436 of the Journal of Hazardous Materials.
Prof. 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 (DE) limits defined by the Ministry of Food and Drug Safety in Korea. 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 the overall weight of the liver. The study recorded lipid, triglyceride, and cholesterol — forms in which fat is stored in the body — buildup in the liver in addition to elevated blood glucose levels with these high levels of EDC exposure. The scientists speculated that the EDCs induced the expression of key genes involved in glucose production and transport pathways, which ultimately impacted liver health.
Since EDC exposure is known to alter liver enzymes, the team examined the levels of blood serum components that are indicative of liver injury. Increased levels of the enzyme aminotransferase were observed upon exposure to EDC mixture levels that were over 25 times the recommended DE level, indicating liver damage. Additionally, an aspartate and alanine aminotransferase ratio of >1 was also observed, which indicated a higher risk of non-alcoholic fatty liver disease and the progression of liver fibrosis owing to an increased deposition of collagen fiber. Moreover, anti-inflammatory cytokines were found to be aggravated in EDC-exposed mice, which resulted in steatohepatitis, a condition where excessive fat accumulates in the liver causing cell death and progression of liver fibrosis. It must be noted here that the mammalian immune system secretes pro-inflammatory cytokines in response to hazardous chemicals, such as EDCs, or infections, thereby contributing to liver inflammation.
Interestingly, markers of oxidative stress and cell death by apoptosis were also observed to be abundant in the EDC-exposed mice. The scientists attributed this to the reduced antioxidant capacity of the liver damaged by the EDCs.
This study is important in that it evaluates the impact of toxic chemicals in real-life scenario, which is much needed to underscore and define their permissible levels in consumer products. “Combined EDC exposure may increase overall EDC ingestion, resulting in significant health consequences,” explains Prof. Pang. What implications might their findings have? “Our study tried to change the conventional toxicological approach and we hope it has an enormous impact on regulatory and public health perspectives,” says Prof. Pang.
Authors: Md Saidur Rahman, Won-Ki Pang, Shehreen Amjad, Do-Yeal Ryu, Elikanah Olusayo Adegoke, Yoo-Jin Park, Myung-Geol Pang
Title of original paper: Hepatic consequences of a mixture of endocrine-disrupting chemicals in male mice
Journal: Journal of Hazardous Materials
Department of Animal Science & 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 culture and arts programs are considered the best in Korea. It was established in 1916. The birth of many disciplines, i.e. pharmacy, business, media, social welfare, arts, etc. began at CAU in Korea. Its new vision for completing 100 years is becoming “The Global Creative Leader.” 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 & Natural Resource are attracting attention globally.
About Professor Myung-Geol Pang
Professor Myung-Geol Pang presently works at the Department of Animal Science and Technology in addition to serving as the Director of the BET Research Institute at Chung-Ang University in South Korea. He holds a Ph.D. in Cellular Endocrinology and Reproductive Biology from Eastern Virginia Medical School, USA. He is a fellow of the prestigious Korean Academy of Science and Technology and has previously held notable research positions in Seoul National University, Korea Advanced Institute of Science and Technology over the course of his career. Prof. Pang and his team have received numerous accolades for their work on environmental health and male fertility.
Read more about Prof. Pang here: https://scholarworks.bwise.kr/cau/researcher-profile?ep=315