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

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

doi:10.3390/toxins11070398

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

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

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

Toxins, Vol.11(7), p.398

07/09/2019

DOI: https://doi.org/10.3390/toxins11070398

PMID: 31323923

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Abstract

Chemical and Drug Induced Liver Injury - etiology

Chemical and Drug Induced Liver Injury - metabolism

Chemical and Drug Induced Liver Injury - pathology

Diet, High-Fat

Fatty Acids - metabolism

Lipid Metabolism - drug effects

Liver - drug effects

Liver - pathology

Liver Cirrhosis, Experimental - etiology

Liver Cirrhosis, Experimental - metabolism

Liver Cirrhosis, Experimental - pathology

Marine Toxins

Microcystins - toxicity

Non-alcoholic Fatty Liver Disease - etiology

Non-alcoholic Fatty Liver Disease - metabolism

Non-alcoholic Fatty Liver Disease - pathology

Rats, Sprague-Dawley

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 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.

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Title: Sub-Chronic Microcystin-LR Liver Toxicity in Preexisting Diet-Induced Nonalcoholic Steatohepatitis in Rats
Creators: Tarana Arman - Washington State University Spokane
Katherine D Lynch - Washington State University Spokane
Michelle L Montonye - Washington State University Spokane
Michael Goedken - Rutgers, The State University of New Jersey
John D Clarke - Washington State University, Department of Pharmaceutical Sciences
Publication Details: Toxins, Vol.11(7), p.398
Academic Unit: Department of Pharmaceutical Sciences
Grant note: R00 ES024455 / NIEHS NIH HHS K99/R00ES024455 / NIH HHS K99 ES024455 / NIEHS NIH HHS
Identifiers: 99901181236201842
Language: English
Resource Type: Journal article