Assessment of diagnostic biomarkers of liver injury in the setting of microcystin-LR (MC-LR) hepatotoxicity

• Published in: Chemosphere (Oxford) 2020-10, Vol.257, p.127111-127111, Article 127111
• Main Authors: Su, Robin C., Lad, Apurva, Breidenbach, Joshua D., Kleinhenz, Andrew L., Modyanov, Nikolai, Malhotra, Deepak, Haller, Steven T., Kennedy, David J.
• Format: Article
• Language: English
• Subjects: ALP; ALT; Diagnostic biomarkers; Liver; Microcystin
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2020.127111

Microcystin-leucine arginine (MC-LR) is a potent liver toxin produced by freshwater cyanobacteria, also known as blue-green algae. While harmful algal blooms are increasing in frequency and severity worldwide, there is still no established method for the diagnosis and assessment of MC-LR induced liver damage. The guidelines for MC-LR safe exposure limits have been previously established based on healthy animal studies, however we have previously demonstrated that pre-existing non-alcoholic fatty liver disease (NAFLD) increases susceptiblity to the hepatotoxic effects of MC-LR. In this study, we sought to investigate the suitability of clinically used biomarkers of liver injury, specifically alanine aminotransferase (ALT) and alkaline phosphatase (ALP), as potential diagnostic tools for liver damage induced by chronic low dose administration of MC-LR in the setting of pre-existing NAFLD. In our Leprdb/J mouse model of NAFLD, we found that while MC-LR induced significant histopathologic damage in the setting of NAFLD, gene expression of ALT and ALP failed to increase with MC-LR exposure. Serum ALT and ALP also failed to increase with MC-LR exposure, except for a moderate increase in ALP with the highest dose of MC-LR used (100 μg/kg). In HepG2 human liver epithelial cells, we observed that increasing MC-LR exposure levels do not lead to an increase in ALT or ALP gene expression, intracellular enzyme activity, or extracellular activity, despite a significant increase in MC-LR induced cytotoxicity. These findings demonstrate that ALT and ALP may be unsuitable as diagnostic biomarkers for MC-LR induced liver damage. [Display omitted] •Effects of MC-LR on ALT and ALP were thoroughly evaluated both In vitro and In vivo.•MC-LR did not appreciably increase the activity or expression of ALT and ALP.•More sensitive and specific diagnostics for MC-LR induced liver injury are needed.