Dose-Response Study of Microcystin Congeners MCLA, MCLR, MCLY, MCRR, and MCYR Administered Orally to Mice

Toxins (Basel). 2021 Jan 24;13(2):86. doi: 10.3390/toxins13020086.

Abstract

Microcystins are common freshwater cyanobacterial toxins that affect liver function. The toxicities of five microcystin congeners (microcystin-LA (MCLA), MCLR, MCLY, MCRR, and MCYR) commonly observed in harmful algal blooms (HABs) were evaluated in BALB/c mice after a single oral administration of doses ranging from those that were no observed adverse effect levels (NOAELs) to lowest observed adverse effect levels (LOAELs). Animals were monitored for changes in behavior and appearance, and euthanized 24 h after dosing. Test endpoints included clinical changes, necropsy observations, and serum indicators of hepatic toxicity and general homeostasis. Doses were 0.5-7 mg/kg MCLA, 0.5-11 mg/kg MCLR, 1-7 mg/kg MCLY, 7-22 mg/kg MCRR, and 3-11 mg/kg MCYR. MCLA at 3 mg/kg elevated liver/body weight ratio and liver score, ALT, AST, and GLDH, indicating hepatic toxicity, reduced serum glucose and highly elevated total serum bilirubin. MCLR and MCLY induced similar effects with LOAELs of 5 mg/kg, although a greater extent and severity of effects were observed in MCLR animals. MCRR exposure at 22 mg/kg was associated with reduced serum glucose. MCYR induced scattered liver effects at 7 mg/kg and reduced serum glucose levels at 5 mg/kg. The results indicate significant differences in congener-induced toxicity after microcystin exposure.

Keywords: cyanobacteria; cyanotoxin; harmful algal bloom; hepatic toxicology; microcystin; mouse; oral administration.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Bilirubin / blood
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Cyanobacteria / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Harmful Algal Bloom
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Marine Toxins / administration & dosage
  • Marine Toxins / toxicity*
  • Mice
  • Mice, Inbred BALB C
  • Microcystins / administration & dosage
  • Microcystins / toxicity*
  • No-Observed-Adverse-Effect Level

Substances

  • Biomarkers
  • Blood Glucose
  • Marine Toxins
  • Microcystins
  • microcystin LY
  • cyanoginosin-LA
  • cyanoginosin LR
  • Bilirubin