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Protective effect of melatonin against mitomycin C-induced genotoxic damage in peripheral blood of rats
S Ortega-Gutiérrez1, M López-Vicente, F Lostalé
1Department of Pharmacology and Physiology, University of Zaragoza, 50009 Zaragoza, Spain.
Abstract:
Mitomycin C (MMC) generates free radicals when metabolized. We investigated the effect of melatonin against MMC-induced genotoxicity in polychromatic erythrocytes and MMC-induced lipid peroxidation in brain and liver homogenates. Rats (N = 36) were classified into 4 groups: control, melatonin, MMC, and MMC + melatonin. Melatonin and MMC doses of 10 mg/kg and 2 mg/kg, respectively, were injected intraperitoneally. Peripheral blood samples were collected at 0, 24, 48, 72, and 96 hours posttreatment and homogenates were obtained at 96 hours posttreatment. The number of micronucleated polychromatic erythrocytes (MN-PCE) per 1000 PCE was used as a genotoxic marker. Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) levels were used as an index of lipid peroxidation. The MMC group showed a significant increase in MN-PCE at 24, 48, 72, and 96 hours that was significantly reduced with melatonin begin coadministrated. No significant differences were found in lipid peroxidation. Our results indicate that MMC-induced genotoxicity can be reduced by melatonin.
Insights
Melatonin effectively reduced Mitomycin C-induced genotoxicity in rats, as shown by fewer micronucleated polychromatic erythrocytes. This study highlights melatonin
Area of Science:
- Toxicology
- Biochemistry
- Pharmacology
Background:
- Mitomycin C (MMC) is a chemotherapeutic agent known to generate free radicals during metabolism.
- Free radical generation by MMC can lead to cellular damage, including genotoxicity.
- Lipid peroxidation is another indicator of oxidative stress that may be induced by MMC.
Purpose of the Study:
- To investigate the protective effects of melatonin against Mitomycin C-induced genotoxicity.
- To assess the impact of melatonin on Mitomycin C-induced lipid peroxidation in rat brain and liver homogenates.
Main Methods:
- Rats were divided into four groups: control, melatonin, MMC, and MMC + melatonin.
- MMC (2 mg/kg) and melatonin (10 mg/kg) were administered intraperitoneally.
- Genotoxicity was assessed by counting micronucleated polychromatic erythrocytes (MN-PCE) in peripheral blood.
- Lipid peroxidation was measured by quantifying malondialdehyde (MDA) and 4-hydroxyalkenal (4-HDA) levels in brain and liver homogenates.
Main Results:
- Mitomycin C administration significantly increased the number of MN-PCE at 24, 48, 72, and 96 hours post-treatment.
- Co-administration of melatonin significantly reduced the MMC-induced increase in MN-PCE.
- No significant differences in lipid peroxidation levels were observed between the groups.
Conclusions:
- Melatonin demonstrates a protective effect against Mitomycin C-induced genotoxicity in polychromatic erythrocytes.
- Melatonin may serve as a potential agent to mitigate the genotoxic side effects of Mitomycin C.
- Further research is needed to elucidate the mechanisms underlying melatonin's protective action and its effects on lipid peroxidation.
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