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

Richard D. Welten, Julie P. Meneely, Olivier P. Chevallier, Vít Kosek, Brett Greer, Jana Hajšlová, Christopher T. Elliott*

*Corresponding author for this work

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Number of pages18
JournalExposure and Health
Early online date02 Dec 2019
DOIs
Publication statusEarly online date - 02 Dec 2019

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pig
Liver
Blood
Swine
Biochemistry
blood
toxin
biochemistry
Metabolomics
Epidemiology
epidemiology
Animals
rodent
bioavailability
Health
cyanobacterium
cancer
Liver Neoplasms
effect
cyanoginosin LR

Keywords

  • Cyanobacteria
  • Cyanotoxins
  • Metabolomics
  • Microcystin-LR
  • Microcystins
  • Toxicity

Cite this

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title = "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.",
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Oral Microcystin-LR Does Not Cause Hepatotoxicity in Pigs: Is the Risk of Microcystin-LR Overestimated? / Welten, Richard D.; Meneely, Julie P.; Chevallier, Olivier P.; Kosek, Vít; Greer, Brett; Hajšlová, Jana; Elliott, Christopher T.

In: Exposure and Health, 02.12.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Oral Microcystin-LR Does Not Cause Hepatotoxicity in Pigs: Is the Risk of Microcystin-LR Overestimated?

AU - Welten, Richard D.

AU - Meneely, Julie P.

AU - Chevallier, Olivier P.

AU - Kosek, Vít

AU - Greer, Brett

AU - Hajšlová, Jana

AU - Elliott, Christopher T.

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Y1 - 2019/12/2

N2 - 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.

AB - 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.

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