Hepatic oxidative stress following prolonged sublethal microcystin LR exposure
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Published on: April 28, 2020
1Department of Veterinary Pathobiology, University of Illinois, Urbana 61802, USA.
Abstract:
Microcystin LR (MCLR) is a naturally occurring protein phosphatase inhibitor and potent hepatotoxin produced by strains of Microcystis aeruginosa. Although its acute toxicity has been well characterized, little is known about its chronic effects. In this study, we sought to acquire evidence that oxidative stress may play a role in the pathogenesis of prolonged sublethal MCLR toxicity. Twelve rats (3 per group) weighing on average 185 g were exposed to 1 of 3 different concentrations of MCLR (16, 32, and 48 microg/kg/day) or to saline via intraperitoneal osmotic pumps for 28 days. Histologic evidence of dose-dependent hepatic inflammation was seen, including infiltration of centrilobular regions by lymphocytes, macrophages, and neutrophils, centrilobular fibrosis, apoptosis, and steatosis. Analysis of lipid peroxidation products revealed a dose-dependent increase in malondialdehyde concentrations with an approximate 4-fold increase in the livers of the high-dose rats over those of the saline-treated controls. Livers from MCLR-exposed rats were more sensitive than those of controls to the cytotoxic effects of the organic oxidizing agent tert-butyl hydroperoxide, based on an MTT (3-[dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) viability assay. These histopathologic and biochemical findings indicate that oxidative stress may play a significant role in the pathogenesis of chronic MCLR toxicosis.
Insights
Chronic exposure to microcystin LR (MCLR), a toxin from Microcystis aeruginosa, causes liver damage and inflammation in rats. Oxidative stress markers increased, suggesting a key role in long-term MCLR toxicity.
Area of Science:
- Environmental Toxicology
- Hepatology
- Oxidative Stress Research
Background:
- Microcystin LR (MCLR) is a potent hepatotoxin produced by Microcystis aeruginosa.
- While acute toxicity is known, chronic effects of MCLR remain under-investigated.
Purpose of the Study:
- To investigate the role of oxidative stress in the pathogenesis of chronic sublethal Microcystin LR toxicity.
Main Methods:
- Rats were exposed to varying concentrations of MCLR (16, 32, 48 microg/kg/day) or saline for 28 days.
- Histopathological analysis examined liver tissue for inflammation, fibrosis, apoptosis, and steatosis.
- Biochemical assays measured lipid peroxidation products (malondialdehyde) and cellular sensitivity to oxidative stress (MTT assay).
Main Results:
- Dose-dependent hepatic inflammation, fibrosis, apoptosis, and steatosis were observed.
- Malondialdehyde concentrations significantly increased in a dose-dependent manner.
- MCLR-exposed livers showed increased sensitivity to tert-butyl hydroperoxide-induced cytotoxicity.
Conclusions:
- Oxidative stress is implicated in the pathogenesis of chronic Microcystin LR toxicosis.
- Prolonged sublethal MCLR exposure induces significant liver damage through oxidative mechanisms.