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Protective effect of melatonin against nodularin-induced oxidative stress
Anna Lankoff1, Anna Banasik, Monika Nowak
1Department of Radiobiology and Immunology, Institute of Biology, Swietokrzyska Academy, Swietokrzyska 15, 25-406 Kielce, Poland. alankoff @pu.kielce.pl
Abstract:
Nodularin is a hepatotoxin from a cyanobacterium, Nodularia spumigena, that inhibits protein phosphatases 1 and 2 and posseses tumor-promoting activity. The aim of this paper was to examine whether nodularin is able to induce oxidative stress in mouse liver tissue and whether melatonin (protective compound against oxidative damage) could supress the activity of nodularin. We studied the effect of nodularin (1, 5, and 10 microg/kg body weight) and melatonin (5, 10, and 15 mg/kg body weight) administration on the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in mouse liver. Intraperitoneal treatment of mice with nodularin per 7 days decreased the activities of all estimated enzymes in a dose-dependent manner. Intraperitoneal treatment of animals with melatonin per 7 days increased the activities of SOD, CAT, and GSH-Px and this effect was concentration-dependent. Co-treatment (nodularin 5 microg/kg body weight + melatonin 5, 10, and 15 mg/kg body weight per 7 days) and post-treatment with melatonin (nodularin 5 microg/kg body weight per 7 days + melatonin 5, 10, and 15 mg/kg body weight per next 7 days) increased the activities of SOD, CAT, and GSH-Px in comparison to the nodularin group. No significant differences from the nodularin group were noted in the group after pre-treatment with melatonin. In conclusion, these findings suggest that oxidative damage may be involved in the toxicity of nodularin. Moreover, co-treatment and post-treatment with 10 and 15 mg/kg body weight of melatonin may protect against nodularin-induced oxidative stress. There was no protective effect of pre-treatment with melatonin.
Insights
Nodularin, a cyanobacterial hepatotoxin, induces oxidative stress in mouse liver by decreasing antioxidant enzyme activity. Melatonin, particularly through co- and post-treatment, shows protective effects against this nodularin-induced damage.
Area of Science:
- Toxicology
- Biochemistry
- Pharmacology
Background:
- Nodularin is a potent hepatotoxin produced by the cyanobacterium Nodularia spumigena.
- It is known to inhibit protein phosphatases 1 and 2 and exhibit tumor-promoting activity.
- Oxidative stress is implicated in the toxicity of various environmental contaminants.
Purpose of the Study:
- To investigate if nodularin induces oxidative stress in mouse liver.
- To determine if melatonin can counteract nodularin's effects.
- To examine the impact of nodularin and melatonin on key antioxidant enzymes.
Main Methods:
- Mice were treated with varying doses of nodularin and melatonin via intraperitoneal injection over 7 days.
- Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were measured in liver tissue.
- Different treatment regimens were employed: nodularin alone, melatonin alone, co-treatment, pre-treatment, and post-treatment.
Main Results:
- Nodularin administration dose-dependently decreased SOD, CAT, and GSH-Px activities.
- Melatonin administration dose-dependently increased SOD, CAT, and GSH-Px activities.
- Co- and post-treatment with melatonin significantly increased antioxidant enzyme activities compared to nodularin alone, while pre-treatment showed no protective effect.
Conclusions:
- Oxidative damage is likely involved in nodularin-induced liver toxicity.
- Melatonin, especially via co- and post-treatment at 10 and 15 mg/kg, demonstrates a protective role against nodularin-induced oxidative stress.
- Pre-treatment with melatonin does not confer protection against nodularin's toxic effects.