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Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the Severity of Liver Disease in Rodents

Meaghan Labine, Yuewen Gong, Gerald Y. Minuk

Abstract

Background. Acute exposure to high concentrations of microcystin-LR (MC-LR) can cause significant hepatocyte injury. Aim. To document the effects of long-term, low-dose MC-LR exposure on hepatic inflammation and fibrosis in mice with healthy and diseased livers. Material and methods. Male CD1 mice (N = 20/group) were exposed to 1.0 μg/L of MC-LR in drinking water; 1.0 μg/L MC-LR plus 300 mg/L of the hepatotoxin thioacetamide (MC-LR/TAA); or 300 mg/L TAA alone for 28 weeks. Liver biochemistry and histology were documented at the end of the study period. In addition, hepatic stellate cells (HSCs), were exposed in vitro to MC-LR (0.1-10,000 μg/L) and monitored for changes in cell metabolism, proliferation and activation. Results. Liver biochemistry and histology were essentially normal in MC-LR alone exposed mice. MC-LR/TAA and TAA alone exposed mice had significant hepatic inflammation and fibrosis but the extent of the changes were similar in the two groups. In vitro, MC-LR had no effect on HSC metabolism, proliferation or activation. Conclusion. Long-term, low-dose exposure to MC-LR is unlikely to lead to chronic liver disease in the setting of a normal liver or exacerbate existing liver disease in the setting of ongoing hepatitis.

Key words. Cyanobacteria., Blue-green algae., Cyanotoxins., Microcystins., Hepatic fibrosis., Cirrhosis., Chronic liver disease., Hepatic stellate cells.

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The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

ALEH Hepatología CASL ACEF Médica Sur
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