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Published on: August 23, 2018
The potential ameliorative effects of melatonin against cyclophosphamide-induced DNA damage in murine bone marrow
M Shokrzadeh1, F Naghshvar, A Ahmadi
1Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Amirhossein_pharma@yahoo.com.
Objectives:
The protection afforded by melatonin, a pineal secretory product, against cyclophosphamide (CP)-induced genotoxicity in murine bone marrow cells was tested using micronuclei as an index of induced chromosomal damage.
Materials And Methods:
Mice were pretreated with four different doses of melatonin (2.5, 5, 10 and 20 mg/kg by weight, b.w.) via intraperitoneal injection for five consecutive days followed by injection with CP (60 mg/kg b.w.) 1 hr after the last injection of melatonin on the fifth day. After 24 hr, mice were euthanized by cervical dislocation to evaluate micronucleated polychromatic erythrocytes (MnPCEs) and the ratio of polychromatic erythrocyte/polychromatic erythrocyte+normochromatic erythrocyte [PCE/(PCE+NCE)]. Histological examination of the bone marrow was also performed.
Results:
Treatment with melatonin significantly reduced the number of MnPCEs induced by CP at all doses (p < 0.0001). At 20 mg/kg, melatonin had a maximum chemoprotective effect and reduced the number of MnPCEs by 6.93 fold and completely normalized the PCE/ (PCE+NCE) ratio. Administration of 20 mg/kg of melatonin led to marked proliferation and hypercellularity of immature myeloid elements after mice were treated with CP, as well as mitigated bone marrow suppression induced by CP.
Conclusions:
Our study revealed that melatonin has a potent antigenotoxic effect against CP-induced toxicity in mice, which may be due to the scavenging of free radicals and increased antioxidant status. Because melatonin is a safe, natural compound, it could be used concomitantly as a supplement to protect people undergoing chemotherapy.
Insights
Melatonin significantly protects against cyclophosphamide-induced genotoxicity in mice by reducing chromosomal damage. This natural compound may serve as a protective supplement during chemotherapy.
Area of Science:
- Toxicology
- Pharmacology
- Genetics
Background:
- Cyclophosphamide (CP) is a widely used chemotherapy agent.
- CP-induced genotoxicity poses a significant risk to patients.
- Melatonin, a natural pineal hormone, possesses antioxidant properties.
Purpose of the Study:
- To evaluate the chemoprotective effects of melatonin against CP-induced genotoxicity.
- To assess melatonin's impact on bone marrow cell damage and recovery.
Main Methods:
- Mice were pretreated with varying doses of melatonin (2.5-20 mg/kg) for five days.
- Cyclophosphamide (60 mg/kg) was administered 1 hour after the final melatonin dose.
- Genotoxicity was assessed by quantifying micronucleated polychromatic erythrocytes (MnPCEs) and bone marrow cellularity.
Main Results:
- Melatonin significantly reduced CP-induced MnPCEs across all tested doses (p < 0.0001).
- The highest dose (20 mg/kg) demonstrated maximum chemoprotection, reducing MnPCEs by 6.93-fold and normalizing the erythrocyte ratio.
- Melatonin treatment mitigated CP-induced bone marrow suppression and promoted myeloid element proliferation.
Conclusions:
- Melatonin exhibits potent antigenotoxic effects against cyclophosphamide-induced toxicity in mice.
- These protective effects are likely mediated by free radical scavenging and enhanced antioxidant status.
- Melatonin's safety and natural origin suggest its potential as a chemoprotective adjunct therapy.
