Identification of Environmental Chemicals Associated with the Development of Toxicant-associated Fatty Liver Disease in Rodents

Abstract

Background Toxicant associated fatty liver disease (TAFLD) is a recently identified form of non-alcoholic fatty liver disease (NAFLD) associated with exposure to industrial chemicals and environmental pollutants. Numerous studies have been conducted to test the association between industrial chemicals/ environmental pollutants and fatty liver disease both in vivo and in vitro. Objectives The objective of the paper is to report a list of chemicals associated with TAFLD. Methods Two federal databases of rodent toxicology studies– ToxRefDB (Environmental Protection Agency) and Chemical Effects in Biological Systems (CEBS, National Toxicology Program) were searched for liver endpoints. Combined, these two databases archive nearly 2000 rodent studies. TASH descriptors including fatty change, fatty necrosis, Oil red O positive staining, steatosis and lipid deposition were queried. Results Using these search terms, 123 chemicals associated with fatty liver were identified. Pesticides and solvents were the most frequently identified chemicals, while PCBs/dioxins were the most potent. About 44% of identified compounds were pesticides or their intermediates, and nearly 10% of pesticide registration studies in ToxRefDB were associated with fatty liver. Fungicides and herbicides were more frequently associated with fatty liver than insecticides. Conclusions More research on pesticides, solvents, metals and PCBs/dioxins in NAFLD/TAFLD is warranted due to their association with liver damage.

Metabolism disrupting chemicals and metabolic disorders

“…In utero and lactational exposure to BPA in a rat model demonstrated a reduction in hepatic glycogen content at 21 weeks of age with evidence that the promoter for hepatic glucokinase was hypermethylated, suggesting a reduction in the expression of this key enzyme [537]. In a multigenerational rat model, BPA exposure in the F0 generation promoted glucose intolerance and insulin resistance in the F2 generation with an associated reduction in hepatic glucokinase expression and concomitant hypermethylation of the gene promoter [547]. Interestingly, adult mice exposed to BPA have also been shown to exhibit reduced hepatic glucokinase activity [548].…”

Hepatoprotective Effect of Microemulsion-Based System of Prunus Cerasus Kernel Extract on CCL4-induced Liver Damage in Mice

“…Hundreds of millions of people worldwide have liver diseases, which are one of the prominent reasons of morbidity and mortality (33). A number of environmental toxicants, chemicals, and drugs can cause se-rious cellular injuries in various organs of the body by metabolic activation (34). CCL 4 is one of the environmental chemicals that cause hepatic injuries.…”

<b>Maternal and fetal toxicity of Wistar rats exposed to herbicide metolachlor

“…A study of Al-Eryani et al (2015) identified 123 chemicals associated with fatty liver. Pesticides and their intermediates corresponded to 44% of these chemicals, and herbicides and fungicides were more frequently associated to this hepatic injury.…”