Hepatic Oxidative Stress Following Prolonged Sublethal Microcystin LR Exposure

Roberto E. Guzman, Philip F. Solter

Research output: Contribution to journalArticlepeer-review


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 μg/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.

Original languageEnglish (US)
Pages (from-to)582-588
Number of pages7
JournalToxicologic Pathology
Issue number5
StatePublished - Sep 1999


  • Alanine aminotransferase
  • apoptosis
  • aspartate aminotransferase
  • cyanobacteria
  • fibrosis
  • lipid peroxidation
  • liver slices
  • malonaldehyde
  • microcystin
  • protein phosphatases 1 and 2A
  • steatosis
  • tert-butylhydroperoxide

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology


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