Sediment pollutant exposures caused hepatotoxicity and disturbed glycogenesis

• Published in: Ecotoxicology and environmental safety Vol. 251; p. 114559
• Main Authors: Lin, Meng-Wei, Yu, Xin-Ru, Chen, Jai-Yu, Wei, Yu-Shan, Chen, Hsin-Yi, Tsai, Yi-Ting, Lin, Li-Hsun, Liao, En-Chi, Kung, Hsiang-Yu, Young, Shuh-Sen, Chan, Hong-Lin, Chou, Hsiu-Chuan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.02.2023; Elsevier
• Subjects: Apoptosis; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - metabolism; Environmental Pollutants - metabolism; Environmental pollution; Glycogen Synthase - metabolism; Glycogen Synthase - pharmacology; Glycogenesis; Humans; Liver; Liver damage; Liver Glycogen - metabolism; Liver Glycogen - pharmacology; Sediment; DMSO; IRS-1; Liver damage; GPT; BSA; DMEM; SD; DSE; GYS; PBS; Glycogenesis; Sediment; HSP; Environmental pollution; IR; Ctrl; GOT; PVDF; DCM; GSK3β; SDS-PAGE; APF; FCS; ROS; Apoptosis
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2023.114559

Liver metabolic syndrome, which involves impaired hepatic glycogen synthesis, is persistently increased by exposure to environmental pollutants. Most studies have investigated the pathogenesis of liver damage caused by single metal species or pure organics. However, under normal circumstances, the pollutants that we are exposed to are usually chemical mixtures that accumulate over time. Sediments are long-term repositories for environmental pollutants due to their environmental cycles, which make them good samples for evaluating the effect of environmental pollutants on the liver via bioaccumulation. This study aimed to clarify the effects of sediment pollutants on liver damage. Our results indicate that industrial wastewater sediment (downstream) is more cytotoxic than sediments from other zones. Downstream sediment extract (DSE) causes hepatotoxicity, stimulates reactive oxygen species (ROS) generation, triggers mitochondrial dysfunction, induces cell apoptosis, and results in the release of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) proteins. Additionally, to elucidate the underlying mechanism by which sediment pollutants disturb hepatic glycogen synthesis, we investigated the effects of different sediment samples from different pollution situations on glycogen synthesis in liver cell lines. It was found that DSE induced multiple severe impairments in liver cells, and disturbed glycogen synthesis more than under other conditions. These impairments include decreased hepatic glycogen synthesis via inhibition and insulin receptor substrate 1 (IRS-1) /AKT /glycogen synthase kinase3β (GSK3β)-mediated glycogen synthase (GYS) inactivation. To our knowledge, this study provides the first detailed evidence of in vitro sediment-accumulated toxicity that interferes with liver glycogen synthesis, leading to hepatic cell damage through apoptosis. •The first in vitro evidence of time-cumulative toxicity linked to liver damage.•Overproduction of reactive oxygen species occurred in polluted human hepatocytes.•Pollution-derived ROS induced mitochondrial dysfunction and hepatic apoptosis.•Medical markers GOT/GPT were released from pollution-derived injured hepatocytes.•Polluted sediment disturbed glycogenesis through insulin resistance pathway.