Hepatic Oxidative Stress Following Prolonged Sublethal Microcystin LR Exposure

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 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.

Oxidative stress response after prolonged exposure of domestic rabbit to a lower dosage of extracted microcystins

“…Usually, cellular oxidative stress is established when the pro-oxidant forces overwhelm the antioxidant defenses (Packer, 1995). Some acute MC exposure tests showed serious oxidative stress in different organs in mammals (Guzman and Solter, 1999;Moreno et al, 2005). In the present study, we detected increased LPO and significant changes of antioxidant enzymes in liver, kidney and brain of domestic animals under prolonged extracted microcystins exposure at a lower dosage.…”

“…This exposure is important since it could become an important form of exposure which is similar with the natural route of potential presence of MCs in daily drinking water. Guzman and Solter (1999) have pointed out that, in the pathogenesis of chronic MC-LR toxicosis, oxidative stress played a significant role. So the aim of this study was to detect the oxidative stress response in domestic animals under the prolonged sub-chronic exposure of low dose of MCs, and to get a broader understanding on the response of different organisms exposed to microcystins in a different exposure way.…”

Plasma biochemical responses of the planktivorous filter-feeding silver carp (Hypophthalmichthys molitrix) and bighead carp (Aristichthys nobilis) to prolonged toxic cyanobacterial blooms in natural waters

“…However, we have revealed that the subcellular organs in hepatocytes of H. molitrix and A. nobilis were in good condition during the blooms (Qiu et al, 2007). A dosedependent-decrease in ALT activity was confirmed on rats after a prolonged sublethal microcystin-LR exposure (Guzman and Solter, 1999), which resulted from the reduction in both ALT protein concentration and ALT mRNA level (Solter et al, 2000). Therefore, the decreasing trends of aminotransferase activities might be due to the alteration of basal gene expression and protein synthesis in phytoplanktivorous fish.…”

Effects of pure microcystin-LR on the transcription of immune related genes and heat shock proteins in larval stage of zebrafish (Danio rerio)

“…One obvious toxic effects of MC-LR is the oxidative stress (Guzman and Solter, 1999;Ding and Ong, 2003;Zegura et al, 2003), and HSPs induction has been suggested as early marker of oxidative stress (Peng et al, 2000). Oxidative stress may occur either due to the over production of reactive oxygen species (ROS) or to decrease of cellular antioxidant levels.…”