Protective Effect of Melatonin Against Mitomycin C‐Induced Genotoxic Damage in Peripheral Blood of Rats

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.

Xanthoria elegans (Link) (lichen) extract counteracts DNA damage and oxidative stress of mitomycin C in human lymphocytes

“…Similar to our findings, MMC was reported to be bioactivated by P450 reductase through one electron reduction and produces oxygen radicals (Seow et al 2004). Ortega-Gutiérrez et al (2009) revealed that MMC generated free radicals when metabolized. Activity of anti-oxidant enzymes like superoxide dismutase (SOD) and glutathione peroxidases (GSH-Px) content had declined after exposure to MMC in blood and liver samples of mice (Li et al 2009).…”

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.…”

“…The induction of SCE is responsible for activating the mechanism to repair double strand breakage, including homologous recombination (HB) (Johnson & Jasin, 2000;Stoilov et al, 2002). The increasing rate of SCE reflects the mutagenic effect of stimulants like radiation or chemical drugs, and this effect on the SCE rate can be reversed by genoprotective agents, including MLT (Assayed & Abd El-Aty, 2009;Awara et al, 1998;Kontek & Nowicka, 2013;Lialiaris et al, 2008;Ortega-Gutiérrez et al, 2009). MLT possesses a variety of mechanisms for genoprotective effects, including direct free radical scavenging, regulation of gene transcription for antioxidative enzymes and induction of DNA repair (Fischer et al, 2008;Tomás-Zapico & Coto-montes, 2005;Vijayalaxmi et al, 1996).…”

“…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).…”

Role of recombinant human erythropoietin against mitomycin C-induced cardiac, hepatic and renal dysfunction in Wistar rats

“…Many efforts have been made to improve the therapeutic index of MMC using pharmacological strategies, such as the administration of melatonin, curcumin, or flavonoid compound like quercitin. [18][19][20] rhEPO, apart its hematopoietic role, has been shown to prevent several injuries. 21,22 In fact, it has been demonstrated that rhEPO receptors are expressed in many tissues, including heart, kidney, and liver.…”