Oral Microcystin-LR Does Not Cause Hepatotoxicity in Pigs: Is the Risk of Microcystin-LR Overestimated?

Abstract

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.