Integrated histopathological and urinary metabonomic investigation of the pathogenesis of microcystin-LR toxicosis

Veterinary Pathology
Glenn H CantorJeremy K Nicholson

Abstract

Patterns of change of endogenous metabolites may closely reflect systemic and organ-specific toxic changes. The authors examined the metabolic effects of the cyanobacterial (blue-green algal) toxin microcystin-LR by (1)H-nuclear magnetic resonance (NMR) analysis of urinary endogenous metabolites. Rats were treated with a single sublethal dose, either 20 or 80 µg/kg intraperitoneally, and sacrificed at 2 or 7 days post dosing. Changes in the high-dose, 2-day sacrifice group included centrilobular hepatic necrosis and congestion, accompanied in some animals by regeneration and neovascularization. By 7 days, animals had recovered, the necrotizing process had ended, and the centrilobular areas had been replaced by regenerative, usually hypertrophic hepatocytes. There was considerable interanimal variation in the histologic process and severity, which correlated with the changes in patterns of endogenous metabolites in the urine, thus providing additional validation of the biomarker and biochemical changes. Similarity of the shape of the metabolic trajectories suggests that the mechanisms of toxic effects and recovery are similar among the individual animals, albeit that the magnitude and timing are different for the individual anim...Continue Reading

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Citations

May 11, 2013·Chemosphere·Xianing HuangKangding Gu
Nov 2, 2015·Journal of Hazardous Materials·Liang ChenPing Xie
Dec 7, 2018·Biomarkers in Medicine·Wen-Tao ZhangXu-Dong Yao
Jun 3, 2021·Environment International·Ya MaHuizhen Zhang
Aug 9, 2021·Ecotoxicology and Environmental Safety·Yuanyuan ZhangLiansheng Wang

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Methods Mentioned

BETA
genetic modification
NMR
blood-draw
PCA
urine collection

Software Mentioned

MATLAB
STOCSY
Xybion Path / Tox System
SIMCA

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