Effects of melatonin on DNA damage induced by cyclophosphamide in rats

Abstract

The antioxidant and free radical scavenger properties of melatonin have been well described in the literature. In this study, our objective was to determine the protective effect of the pineal gland hormone against the DNA damage induced by cyclophosphamide (CP), an anti-tumor agent that is widely applied in clinical practice. DNA damage was induced in rats by a single intraperitoneal injection of CP (20 or 50 mg/kg). Animals received melatonin during the dark period for 15 days (1 mg/kg in the drinking water). Rat bone marrow cells were used for the determination of chromosomal aberrations and of formamidopyrimidine DNA glycosylase enzyme (Fpg)-sensitive sites by the comet technique and of Xpf mRNA expression by qRT-PCR. The number (mean ± SE) of chromosomal aberrations in pinealectomized (PINX) animals treated with melatonin and CP (2.50 ± 0.50/100 cells) was lower than that obtained for PINX animals injected with CP (12 ± 1.8/100 cells), thus showing a reduction of 85.8% in the number of chromosomal aberrations. This melatonin-mediated protection was also observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both 24 and 48 h after CP administration. The expression of Xpf mRNA, which is involved in the DNA nucleotide excision repair machinery, was up-regulated by melatonin. The results indicate that melatonin is able to protect bone marrow cells by completely blocking CP-induced chromosome aberrations. Therefore, melatonin administration could be an alternative and effective treatment during chemotherapy.

Hepatoprotective and antiapoptotic role of aged black garlic against hepatotoxicity induced by cyclophosphamide

“…Many investigations have reported that CP induces gene mutations, DNA strand breaks, chromosome aberrations, micronuclei and sister chromatid exchanges, apoptosis, and generation of free radicals (Ferreira et al, 2013). Data are represented as mean ± SD, n = 7 *Significant increase at P < 0.05 compared with the control group **Significant decrease at P < 0.05 compared with the cyclophosphamide group CP-induced hepatocytes apoptosis was investigated by Alqahtani and Mahmoud (2016) as they determined immunohistochemically both gene and protein expression levels of the proapoptotic factors caspase-3 and BAX.…”

Protective effects of melatonin-loaded lipid-core nanocapsules on paraquat-induced cytotoxicity and genotoxicity in a pulmonary cell line

“…Mel may also enhance repair of strand breaks caused by methyl methanesulfonate (MMS) in the breast cancer cell line MCF-7, by regulation of several key genes responsible for DNA damage repair [16]. Moreover, Mel confers protection from oxidative DNA damage caused by cyclophosphamide in rats [44]. The greater effects of Mel-LNC in comparison with Mel could be explained due to the mechanism of distribution of melatonin when associated with nanocapsules and the antioxidant properties of LNC per se.…”

In vitroandin vivoeffects of melatonin on sister chromatid exchange in human blood lymphocytes exposed to hypoxia

“…MLT is also called N-acetyl-5-methoxytryptamine (MLT) and it is synthesized by the pineal gland in the brain where it participates in the regulation of a number of important physiological and pathological processes in mammals (Reiter, 1991). Various studies have confirmed that MLT has a protective effect against DNA damage, although the mechanisms by which MLT produced such protective effects are not clear (Assayed & Abd El-Aty, 2009;Awara et al, 1998;Erenberk et al, 2014;Ferreira et al, 2013;Kontek & Nowicka, 2013;Lialiaris et al, 2008;Ortega-Gutiérrez et al, 2009;Purohit & Rao, 2014;Vijayalaxmi et al, 1995). The aim of this study is to clarify whether MLT has a protective effect against hypoxia at the cytogenetic level by examining SCE formation both in vitro and in vivo.…”

“…Previous studies have described that MLT is an anti-mutagenic agent against a variety of toxic stimulations (Carbamazepine, radiation and melphalan) in vitro (Assayed & Abd El-Aty, 2009;Awara et al, 1998;Erenberk et al, 2014;Kontek & Nowicka, 2013;Lialiaris et al, 2008;Ortega-Gutiérrez et al, 2009;Purohit & Rao, 2014). According to the data, some chemicals for the treatment increased the frequency of SCE due to their cytotoxic effect; however, co-treatment of MLT may prevent the DNA damage via various mechanisms like JAK2/STAT3 signaling (Awara et al, 1998;Duan et al, 2013;Ferreira et al, 2013;Lialiaris et al, 2008). Though hypoxia is the most important factor causing DNA damage in various tissues, there was little study about the effect of MLT against hypoxia by using cytogenetic methods.…”