Chlordecone potentiates hepatic fibrosis in chronic liver injury induced by carbon tetrachloride in mice

Abstract

Chronic liver damage due to viral or chemical agents leads to a repair process resulting in hepatic fibrosis. Fibrosis may lead to cirrhosis, which may progress to liver cancer or a loss of liver function, with an associated risk of liver failure and death. Chlordecone is a chlorinated pesticide used in the 1990s. It is not itself hepatotoxic, but its metabolism in the liver triggers hepatomegaly and potentiates hepatotoxic agents. Chlordecone is now banned, but it persists in soil and water, resulting in an ongoing public health problem in the Caribbean area. We assessed the probable impact of chlordecone on the progression of liver fibrosis in the population of contaminated areas, by developing a mouse model of chronic co-exposure to chlordecone and a hepatotoxic agent, carbon tetrachloride (CCl4). After repeated administrations of chlordecone and CCl4 by gavage over a 12-week period, we checked for liver damage in the exposed mice, by determining serum liver transaminase (AST, ALT) levels, histological examinations of the liver and measuring the expression of genes encoding extracellular matrix components. The co-exposure of mice to CCl4 and chlordecone resulted in significant increases in ALT and AST levels. Chlordecone also increased expression of the Col1A2, MMP-2, TIMP-1 and PAI-1 genes in CCl4-treated mice. Finally, we demonstrated, by quantifying areas of collagen deposition and alpha-SMA gene expression, that chlordecone potentiated the hepatic fibrosis induced by CCl4. In conclusion, our data suggest that chlordecone potentiates hepatic fibrosis in mice with CCl4-induced chronic liver injury.

Moderate chronic ethanol consumption exerts beneficial effects on nonalcoholic fatty liver in mice fed a high-fat diet: possible role of higher formation of triglycerides enriched in monounsaturated fatty acids

“…In order to have more information regarding fibrosis, deposition of fibrillary collagen was assessed by using second-harmonic generation (SHG) microscopy available at the light microscopyimaging center (MRic facility of Biosit, University of Rennes 1), as previously described [24,25].…”

Differential Proteomic Analysis of Dimethylnitrosamine (DMN)‐Induced Liver Fibrosis

“…After a 4‐week treatment, the rats were sacrificed immediately under anesthesia after an overnight fast. The liver index (liver wet weight/body weight) and spleen index (spleen wet weight/body weight) were calculated, and serum and liver samples were collected prior to further analysis . All animal experiments in this study were approved by the ethics committee of the school of life, Beijing Institute of Technology (Beijing, China).…”

Lindane, kepone and pentachlorobenzene: chloropesticides banned by Stockholm convention

“…It is also neurotoxicant and is provokes seizures at the concentration of 1.9 lg/mL of blood (Croom et al 2015). Kepone on the other hand is cancerogenic and hepatotoxic in mice and rats (Tabet et al 2016;Fournier et al 2017) and affects also their reproductive capabilities at high chlordecone concentrations (Brown et al 1991).…”