The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ Toxicity

Microcystins (MCs) are common cyanobacterial toxins that occur in freshwaters worldwide. Only two of the >200 MC variants have been tested for potential toxicity after oral exposure. This paper reports on the toxicity of 10 different MC congeners identified in algal blooms, microcystin-LR (MCLR),...

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Main Authors: Neil Chernoff, Donna Hill, Johnsie Lang, Judy Schmid, Thao Le, Amy Farthing, Hwa Huang
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/12/6/403
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author Neil Chernoff
Donna Hill
Johnsie Lang
Judy Schmid
Thao Le
Amy Farthing
Hwa Huang
author_facet Neil Chernoff
Donna Hill
Johnsie Lang
Judy Schmid
Thao Le
Amy Farthing
Hwa Huang
author_sort Neil Chernoff
collection DOAJ
description Microcystins (MCs) are common cyanobacterial toxins that occur in freshwaters worldwide. Only two of the >200 MC variants have been tested for potential toxicity after oral exposure. This paper reports on the toxicity of 10 different MC congeners identified in algal blooms, microcystin-LR (MCLR), MCLA, MCLF, MCLW, MCLY, MCRR, [Asp3]MCRR, [Asp3,Dhb7]MCRR, MCWR, and MCYR after single administrations to BALB/c mice. In a preliminary MCLR dose–response study of 3 to 9 mg/kg doses, ≥5 mg/kg induced clinical changes, increased serum levels of ALT, AST, and GLDH, liver congestion, increased liver/body weight ratios, and reduced serum glucose and total protein. Based on the extent of these effects, the 10 congeners were administered as single 7 mg/kg oral doses and toxicity evaluated. The greatest toxicity was observed with MCLA and MCLR including a high percentage of moribundity. In addition to eliciting effects similar to those listed above for MCLR, MCLA also induced serum alterations indicative of jaundice. MCLY, and MCYR induced changes like those noted with MCLR, but to lesser extents. MCLW and MCLF exhibited some serum and morphological changes associated with hepatic toxicity, while there were few indications of toxicity after exposures to MCRR, [Asp<sup>3</sup>]MCRR, [Asp<sup>3</sup>,Dhb<sup>7</sup>]MCRR, or MCWR. These data illustrate a wide spectrum of hepatic effects and different potencies of these MC congeners.
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spelling doaj.art-8b06b377eaf742dd9df9bb0b49e95fa12023-11-20T04:13:24ZengMDPI AGToxins2072-66512020-06-0112640310.3390/toxins12060403The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ ToxicityNeil Chernoff0Donna Hill1Johnsie Lang2Judy Schmid3Thao Le4Amy Farthing5Hwa Huang6Center for Public Health & Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USACenter for Public Health & Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USAOak Ridge Institute for Science and Education, Oak Ridge, TN 37830, USACenter for Public Health & Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USAOak Ridge Institute for Science and Education, Oak Ridge, TN 37830, USAOak Ridge Institute for Science and Education, Oak Ridge, TN 37830, USAOak Ridge Institute for Science and Education, Oak Ridge, TN 37830, USAMicrocystins (MCs) are common cyanobacterial toxins that occur in freshwaters worldwide. Only two of the >200 MC variants have been tested for potential toxicity after oral exposure. This paper reports on the toxicity of 10 different MC congeners identified in algal blooms, microcystin-LR (MCLR), MCLA, MCLF, MCLW, MCLY, MCRR, [Asp3]MCRR, [Asp3,Dhb7]MCRR, MCWR, and MCYR after single administrations to BALB/c mice. In a preliminary MCLR dose–response study of 3 to 9 mg/kg doses, ≥5 mg/kg induced clinical changes, increased serum levels of ALT, AST, and GLDH, liver congestion, increased liver/body weight ratios, and reduced serum glucose and total protein. Based on the extent of these effects, the 10 congeners were administered as single 7 mg/kg oral doses and toxicity evaluated. The greatest toxicity was observed with MCLA and MCLR including a high percentage of moribundity. In addition to eliciting effects similar to those listed above for MCLR, MCLA also induced serum alterations indicative of jaundice. MCLY, and MCYR induced changes like those noted with MCLR, but to lesser extents. MCLW and MCLF exhibited some serum and morphological changes associated with hepatic toxicity, while there were few indications of toxicity after exposures to MCRR, [Asp<sup>3</sup>]MCRR, [Asp<sup>3</sup>,Dhb<sup>7</sup>]MCRR, or MCWR. These data illustrate a wide spectrum of hepatic effects and different potencies of these MC congeners.https://www.mdpi.com/2072-6651/12/6/403HABcyanobacteriacyanotoxinmicrocystinhepatic toxicologyoral administration
spellingShingle Neil Chernoff
Donna Hill
Johnsie Lang
Judy Schmid
Thao Le
Amy Farthing
Hwa Huang
The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ Toxicity
Toxins
HAB
cyanobacteria
cyanotoxin
microcystin
hepatic toxicology
oral administration
title The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ Toxicity
title_full The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ Toxicity
title_fullStr The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ Toxicity
title_full_unstemmed The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ Toxicity
title_short The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ Toxicity
title_sort comparative toxicity of 10 microcystin congeners administered orally to mice clinical effects and organ toxicity
topic HAB
cyanobacteria
cyanotoxin
microcystin
hepatic toxicology
oral administration
url https://www.mdpi.com/2072-6651/12/6/403
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