Journal Article

Sub-Chronic Microcystin-LR Liver Toxicity in Preexisting Diet-Induced Nonalcoholic Steatohepatitis in Rats

Lynch, Katherine D., Clarke, John D., Arman, Tarana, Montonye, Michelle L., Goedken, Michael

2019

Overview

Microcystin-LR (MCLR) is a hepatotoxic cyanotoxin reported to cause a phenotype similar to nonalcoholic steatohepatitis (NASH). NASH is a common progressive liver disease that advances in severity due to exogenous stressors such as poor diet and toxicant exposure. Our objective was to determine how sub-chronic MCLR toxicity affects preexisting diet-induced NASH. Sprague-Dawley rats were fed one of three diets for 10 weeks: control, methionine and choline deficient (MCD), or high fat/high cholesterol (HFHC). After six weeks of diet, animals received vehicle, 10 µg/kg, or 30 µg/kg MCLR via intraperitoneal injection every other day for the final 4 weeks. Incidence and severity scoring of histopathology endpoints suggested that MCLR toxicity drove NASH to a less fatty and more fibrotic state. In general, expression of genes involved in de novo lipogenesis and fatty acid esterification were altered in favor of decreased steatosis. The higher MCLR dose increased expression of genes involved in fibrosis and inflammation in the control and HFHC groups. These data suggest MCLR toxicity in the context of preexisting NASH may drive the liver to a more severe phenotype that resembles burnt-out NASH.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Chemical and Drug Induced Liver Injury - etiology / Chemical and Drug Induced Liver Injury - metabolism / Chemical and Drug Induced Liver Injury - pathology / Cholesterol / Choline / Cyanobacteria / Diabetes / Diet / Diet, High-Fat / Esterification / Fatty acids / Fatty Acids - metabolism / Fibrosis / Gene expression / Genes / Glucose / Histopathology / Hypoglycemia / Inflammation / Insulin resistance / Lipid Metabolism - drug effects / Lipogenesis / Liver / Liver - drug effects / Liver - pathology / Liver cancer / Liver Cirrhosis, Experimental - etiology / Liver Cirrhosis, Experimental - metabolism / Liver Cirrhosis, Experimental - pathology / Liver diseases / Male / Marine Toxins / Metabolism / Metabolites / Methionine / Microcystin-LR / Microcystins / Microcystins - toxicity / Non-alcoholic Fatty Liver Disease - etiology / Non-alcoholic Fatty Liver Disease - metabolism / Non-alcoholic Fatty Liver Disease - pathology / nonalcoholic steatohepatitis / Pathogenesis / Phenotypes / Plasma / Protein expression / Proteins / Rats, Sprague-Dawley / Spleen / Steatosis / sub-chronic toxicity / Toxicants / Toxicity / Triglycerides