Microcystin-LR and its health impacts: Chemistry, transmission routes, mechanisms of toxicity and target organs
Roshni Rajpoot, Siddharth Rajput, Raj Kumar Koiri
Abstract
Microcystin-LR, a hepatotoxin produced by cyanobacteria, poses significant health risks to humans and other animals through various routes of exposure. This review comprehensively explores the chemistry, transmission pathways, mechanisms of toxicity, and target organs affected by MC-LR to provide a detailed understanding of its health impacts on animals and humans. MC-LR exposure occurs through different transmission routes, including ingestion of contaminated water and food, algal dietary supplements, direct body contact with harmful algal blooms, and inhalation of aerosolized toxins. In this review, we explored that the toxic effects of MC-LR are mediated through multiple complex mechanisms. A key mechanism of its toxicity is the inhibition of protein phosphatases PP1 and PP2A which results in abnormal cellular signalling pathways. Additionally, MC-LR induces oxidative stress and disrupts cellular homeostasis. The findings suggest that MC-LR modulates the activity of various antioxidant enzymes and also activates apoptosis pathways by different mechanisms. It also induces cytoskeletal disruption, ultimately compromising cellular integrity and function. MC-LR also induces activation of oncogenes such as Gankyrin, PI3K/AKT, HIF-1α, RAC1/JNK and NEK2 pathway and upregulates the inflammatory molecules such as NF-κβ, and TNF-α, hence leading to carcinogenesis. MC-LR has toxicological effects on multiple organs . The liver is the primary target, where MC-LR accumulates and causes hepatotoxicity, but other organs are affected as well. MC-LR shows neurotoxicity, nephrotoxicity, cardiotoxicity and reproductive toxicity. • In the MC family, Microcystin-leucine arginine (MC-LR) is the most common and toxic compound. • MC-LR causes toxicity in different organs such as the liver, brain, kidney, lung, intestine, heart and gonads. • MC-LR toxicity mechanisms involves PP1/PP2A inhibition, oxidative stress, oncogenic & apoptosis pathways, and cytoskeleton disruption. • Long-term exposure to low concentrations of MCs increases the risk of cancer development.