Journal Article

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

Lang, Johnsie, Schmid, Judith, Farthing, Amy, Huang, Hwa, Chernoff, Neil, Hill, Donna

2021

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Administration, Oral / Algae / Algal blooms / Amino acids / Animals / Apoptosis / Aquatic ecosystems / Bilirubin / Bilirubin - blood / Biomarkers - blood / Blood Glucose - drug effects / Blood Glucose - metabolism / Body weight / Chemical and Drug Induced Liver Injury - etiology / Chemical and Drug Induced Liver Injury - metabolism / Chemical and Drug Induced Liver Injury - pathology / Congeners / Cyanobacteria / Cyanobacteria - metabolism / cyanotoxin / Dosage / Dose-Response Relationship, Drug / Eutrophication / Female / Glucose / Harmful Algal Bloom / hepatic toxicology / Homeostasis / Liver / Liver - drug effects / Liver - metabolism / Liver - pathology / Male / Marine Toxins - administration & dosage / Marine Toxins - toxicity / Mice / Mice, Inbred BALB C / microcystin / Microcystins / Microcystins - administration & dosage / Microcystins - toxicity / Necropsy / No-Observed-Adverse-Effect Level / Oral administration / Phosphatase / Proteins / Side effects / Toxicity / Toxicology / Toxins / Water quality