Preventive and curative effect of melatonin on mammary carcinogenesis induced by dimethylbenz[a]anthracene in the female Sprague–Dawley rat

INTRODUCTION: It has been well documented that the pineal hormone, melatonin, which plays a major role in the control of reproduction in mammals, also plays a role in the incidence and growth of breast and mammary cancer. The curative effect of melatonin on the growth of dimethylbenz [a]anthracene-induced (DMBA-induced) mammary adenocarcinoma (ADK) has been previously well documented in the female Sprague–Dawley rat. However, the preventive effect of melatonin in limiting the frequency of cancer initiation has not been well documented. METHODS: The aim of this study was to compare the potency of melatonin to limit the frequency of mammary cancer initiation with its potency to inhibit tumor progression once initiation, at 55 days of age, was achieved. The present study compared the effect of preventive treatment with melatonin (10 mg/kg daily) administered for only 15 days before the administration of DMBA with the effect of long-term (6-month) curative treatment with the same dose of melatonin starting the day after DMBA administration. The rats were followed up for a year after the administration of the DMBA. RESULTS: The results clearly showed almost identical preventive and curative effects of melatonin on the growth of DMBA-induced mammary ADK. Many hypotheses have been proposed to explain the inhibitory effects of melatonin. However, the mechanisms responsible for its strong preventive effect are still a matter of debate. At least, it can be envisaged that the artificial amplification of the intensity of the circadian rhythm of melatonin could markedly reduce the DNA damage provoked by DMBA and therefore the frequency of cancer initiation. CONCLUSION: In view of the present results, obtained in the female Sprague–Dawley rat, it can be envisaged that the long-term inhibition of mammary ADK promotion by a brief, preventive treatment with melatonin could also reduce the risk of breast cancer induced in women by unidentified environmental factors

Differential effects of melatonin as a broad range UV-damage preventive dermato-endocrine regulator

Melatonin or N-acetyl-5-methoxytryptamine, is a compound derived from tryptophan that is found in all organisms from single cells to vertebrates and the human. It is one of the most evolutionarily conserved and pleiotropic hormone still active in humans and has been implicated in vital skin functions such as hair growth, fur pigmentation as well as melanoma control. Being a main secretory product of the pineal gland, melatonin regulates seasonal biorhythms, reproductive mechanisms or mammary gland metabolism. Due to its wide range endocrine properties it is also recognized to modulate numerous additional functions ranging from scavenging free radicals, immunomodulation-mediated DNA repair, wound healing, involvement in gene expression connected with circadian clocks and modulation of secondary endocrine signaling including prolactin release. Recently, apart from above mentioned entities, it was shown that melatonin suppresses ultraviolet (UV)-induced damage in human skin and human derived cell lines (e.g., keratinocytes, fibroblasts). The magnitude of UV-induced damage is mediated apparently by various molecular mechanisms related to generation of reactive oxygen species (ROS), apoptosis and mitochondrial-mediated cell death which are all counteracted or modulated by melatonin. We provide here an update of the relevant protective effects and molecular mechanisms of action of melatonin in the skin

Role of Melatonin in Regulating Matrix Metalloproteinase-9 Via Tissue Inhibitors of Metalloproteinase-1 During Protection against endometriosis

Endometriosis is a gynecological disease of women and plausibly Nregulated by matrix metalloproteinases (MMPs). However, mechanisms of alterations in MMPs during endometriosis remain unclear. Human endometriotic tissues possessing varying degrees of severity were examined for expression of MMPs and tissue inhibitors of metalloproteinase (TIMP)-1. In addition, endometriosis was generated in mice and endometriotic tissues were tested for MMP-9 activity. Results show significant upregulation of secreted and synthesized proMMP-9 activity with duration and severity of endometriosis. Along with upregulation of activity, the expression of proMMP-9 was found increased while TIMP-1 expression followed an inverse trend. The effect of melatonin, a major secretory product of the pineal gland, on endometriosis was examined in preventive and therapeutic models in mice. The results show that melatonin arrested lipid peroxidation and protein oxidation and downregulated proMMP-9 activity and expression in a time and dose-dependent manner while protecting and regressing peritoneal endometriosis. Moreover, the attenuated activity and expression of proMMP-9 were associated with subsequent elevation in the expression of TIMP-1. Our study reveals for the first time the role of melatonin in arresting peritoneal endometriosis in mice and a novel marker, expression ratio of proMMP-9 versus TIMP-1, was identified for assessing severity and progression of endometriosis

Overweight in young males reduces in a half the normal pregnancy success in rabbit model

[EN] Semen quality has certainly declined over the past few decades, possibly owing to modern lifestyle factors. In this sense, the role of overweight and obesity in the development of subfertility in males has generated a considerable amount of interest in recent years. However, there is no consensus on whether overweight or obesity impaired sperm quality. Thus, based on the ongoing debate about risk factors for subfertility associated with overweight and obesity in men, this study was designed to investigate the effect of overweight on sperm quality parameters and fertility success in randomized controlled trial in a rabbit model. Fourteen male rabbits were randomly assigned to a control group in which nutritional requirements were satisfied or a group fed to satiety from 12 to 32 weeks of age. At 24 weeks of age, semen samples were analysed weekly by conventional semen analysis for 8 weeks. In addition, during the trial female rabbits were artificially inseminated by each male to assess the fertility success and the number of offspring. Young males fed to satiety were associated with a significant increase in body weight (13.6% overweight) and perirenal fat thickness (5%). Male overweight presented a significant decrease in sperm concentration. There were no differences in the remaining sperm parameters. However, male overweight showed a clear and significant decrease in fertility success (control group, 64±8.9% versus fed to satiety group, 35±9.2%), but not in the number of offspring. Taken together, our findings provide new evidence on the loss of fertility induced by overweight in males.This research was supported by the projects: Spanish Research project AGL2014-5 3405-C2-1-P Comision Interministerial de Ciencia y Tecnologia (FMJ, JSV). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Marco-Jiménez, F.; Vicente Antón, JS. (2017). Overweight in young males reduces in a half the normal pregnancy success in rabbit model. PLoS ONE. 12(7):1-11. https://doi.org/10.1371/journal.pone.0180679S11112