The potential ameliorative effects of melatonin against cyclophosphamide-induced DNA damage in murine bone marrow cells

M. Shokrzadeh, F. Naghshvar, A. Ahmadi, A. Chabra, F. Jeivad

Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Amirhossein_pharma@yahoo.com

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• Pharmacology

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.

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