Cyanobacterial toxins are a growing threat to human and animal welfare in many parts of the world. Microcystin-LR is the most widely studied of the cyanotoxins and has been implicated with hepatotoxicity, neuropathology, and genotoxicity. Numerous studies investigated the effect of microcystin-LR exposure on the proteome using various animal models, and together they form a large database of potential protein biomarkers. However, it is extremely difficult to establish which proteins are specifically affected by microcystin-LR, and which represent a more general toxin response. The goal of this review was to filter out inconsistently reported protein abundancy changes after microcystin-LR exposure. We explored online search engines for studies investigating the effect of microcystin-LR toxicity on the proteome. The selected studies were examined to find overlapping protein abundancy changes. The protein names, their synonyms, and relevant orthologues were used as search terms. This review has produced, for the first time, a comprehensive list of proteins whose abundancies changed in at least two proteomic studies investigating microcystin-LR toxicity in rodents and zebrafish. Proteins involved in oxidoreductase activity and cytoskeletal processes are persistently affected by microcystin-LR exposure. Several oxidative stress markers are consistently altered across multiple proteomic studies, which correlates with findings from epidemiological studies that linked chronic microcystin exposure to increased incidences of liver and colorectal cancer. This study unveils which proteins' abundancies are consistently altered after microcystin-LR exposure and opens new doors to understanding the mechanisms behind microcystin-LR toxicity.

The global increase of toxin-producing cyanobacteria poses a serious risk to humans. Many investigations have shown that the cyanotoxin microcystin-LR induces hepatotoxicity in rodents. However, many of these studies applied the toxin intraperitoneally or used high oral concentrations, leading to an unrealistically high bioavailability of the toxin. Such approaches have put into question how these results translate to human exposure scenarios. Epidemiology studies have linked microcystin-LR with hepatotoxicity and liver cancer in humans, though by design these investigations cannot provide direct evidence. The present work investigated the effect of microcystin-LR exposure on pigs closely mimicking real-life human conditions. In two animal experiments, pigs were administered microcystin-LR daily by oral gavage for 35 days. Metabolomic and lipidomic tools were used to analyse blood and liver samples. In addition, blood biochemistry parameters indicative of liver function and health were studied to further investigate the potential hepatotoxic effects of microcystin-LR. Results indicated that the metabolomic and lipidomic analyses did not show a gross treatment effect in blood and liver. Furthermore, no significant alterations were found in the tested blood biochemistry parameters. No evidence of hepatotoxicity was found. These results shed more light onto the effects (or lack of effects) of low-dose oral microcystin-LR exposure. The data suggests that the risk of oral microcystin-LR exposure may be overestimated.