This page has only limited features, please log in for full access.
Microcystins are ubiquitous toxins produced by photoautotrophic cyanobacteria. Human exposures to microcystins occur through the consumption of contaminated drinking water, fish and shellfish, vegetables, and algal dietary supplements and through recreational activities. Microcystin-leucine-arginine (MCLR) is the prototypical microcystin because it is reported to be the most common and toxic variant and is the only microcystin with an established tolerable daily intake of 0.04 µg/kg. Microcystin toxicokinetics is characterized by low intestinal absorption, rapid and specific distribution to the liver, moderate metabolism to glutathione and cysteinyl conjugates, and low urinary and fecal excretion. Molecular toxicology involves covalent binding to and inhibition of protein phosphatases, oxidative stress, cell death (autophagy, apoptosis, necrosis), and cytoskeleton disruption. These molecular and cellular effects are interconnected and are commonly observed together. The main target organs for microcystin toxicity are the intestine, liver, and kidney. Preclinical data indicate microcystins may also have nervous, pulmonary, cardiac, and reproductive system toxicities. Recent evidence suggests that exposure to other hepatotoxic insults could potentiate microcystin toxicity and increase the risk for chronic diseases. This review summarizes the current knowledge for microcystin toxicokinetics, molecular toxicology, and pathophysiology in preclinical rodent models and humans. More research is needed to better understand human toxicokinetics and how multifactorial exposures contribute to disease pathogenesis and progression.
Tarana Arman; John Clarke. Microcystin Toxicokinetics, Molecular Toxicology, and Pathophysiology in Preclinical Rodent Models and Humans. Toxins 2021, 13, 537 .
AMA StyleTarana Arman, John Clarke. Microcystin Toxicokinetics, Molecular Toxicology, and Pathophysiology in Preclinical Rodent Models and Humans. Toxins. 2021; 13 (8):537.
Chicago/Turabian StyleTarana Arman; John Clarke. 2021. "Microcystin Toxicokinetics, Molecular Toxicology, and Pathophysiology in Preclinical Rodent Models and Humans." Toxins 13, no. 8: 537.
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.
Tarana Arman; Katherine D. Lynch; Michelle L. Montonye; Michael Goedken; John D. Clarke. Sub-Chronic Microcystin-LR Liver Toxicity in Preexisting Diet-Induced Nonalcoholic Steatohepatitis in Rats. Toxins 2019, 11, 398 .
AMA StyleTarana Arman, Katherine D. Lynch, Michelle L. Montonye, Michael Goedken, John D. Clarke. Sub-Chronic Microcystin-LR Liver Toxicity in Preexisting Diet-Induced Nonalcoholic Steatohepatitis in Rats. Toxins. 2019; 11 (7):398.
Chicago/Turabian StyleTarana Arman; Katherine D. Lynch; Michelle L. Montonye; Michael Goedken; John D. Clarke. 2019. "Sub-Chronic Microcystin-LR Liver Toxicity in Preexisting Diet-Induced Nonalcoholic Steatohepatitis in Rats." Toxins 11, no. 7: 398.