Activity and gene expression profile of certain antioxidant enzymes to microcystin-LR induced oxidative stress in mice.
Microcystins are cyclic heptapeptide toxins produced by certain strains of Microcystis aeruginosa and microcystin-LR (MC-LR) is the most toxic among the 70 variants isolated so far. These toxins have been implicated in both human and livestock mortality. In the present study we investigated the microcystin-LR induced oxidative stress in mice in terms of its effect on activity and gene expression profile of certain antioxidant enzymes and expression of heat shock protein-70 (HSP-70). Mice were treated with 0.5 LD50 (38.31 microg/kg) and 1 LD50 (76.62 microg/kg) and the biochemical variables were determined at 1, 3, 7 days and 15, 30, 60 and 120 min post-exposure for 0.5 and 1 LD50 dose, respectively. A significant time-dependent increase in HSP-70 expression over control was observed at 1 LD50 dose. The toxin induced significant increase in liver body weight index, hepatic lipid peroxidation and depletion of GSH levels at 1 LD50 compared to control group. There was significant decrease in the activity of antioxidant enzymes glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione-S-transferase (GST) at 1 LD50. Except catalase, there was no effect on other antioxidant enzymes at 0.5 LD50 dose. In contrast to activity of antioxidant enzymes the gene expression profile did not show any significant difference compared to control at 1 LD50. GR showed significant decrease in expression at 1, 3 and 7 days in animals dosed with 0.5 LD50 MC-LR. The results of our in vivo study clearly show the oxidative stress induced by MC-LR, and a correlation with activity and regulation at gene expression level of antioxidant enzymes.
Jayaraj
R
R
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
Anand
T
T
Rao
P V Lakshmana
PV
D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D005981:Glutathione Synthase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007928:Lethal Dose 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008387:Marine Toxins; D051379:Mice; D052998:Microcystins; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010456:Peptides, Cyclic / Q000633:toxicity*
D018840:HSP70 Heat-Shock Proteins; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D010088:Oxidoreductases; D005982:Glutathione Transferase; D005981:Glutathione Synthase; C057862:cyanoginosin LR; D005978:Glutathione