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      Melatonin receptor 1A gene polymorphism rs13140012 and serum melatonin in atherosclerotic versus non-atherosclerotic Egyptian ESRD patients: pilot study

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          Abstract

          Aim

          To study the relationship between melatonin levels and Melatonin membrane receptor 1A ( MTNR1A) SNP (rs13140012) in end-stage renal disease patients (ESRD) in Alexandria, Egypt on maintenance hemodialysis with or without atherosclerosis.

          Materials and methods

          40 end-stage renal disease patients on regular hemodialysis were divided into 2 subgroups, one with (n = 20) and one without atherosclerosis (n = 20) and normal subjects (n = 40). Serum melatonin, carotid intimal medial thickness (CIMT) were measured. Melatonin membrane receptor 1A ( MTNR1A) SNP (rs13140012) genotyping was done using 5'nuclease Allelic discrimination.

          Results

          Serum melatonin was significantly lower in ESRD patients [1.6 to 11.30 (pg/mL) with a median of 2.5] than the control group [20.50 to 56.40 (pg/mL) with a median of 35.20]. Serum melatonin was significantly lower in atherosclerotic patients subgroup [1.6–2.50 (pg/mL) with a median value of 2.30] than non-atherosclerotic patients subgroup [2.0–11.30 (pg/mL) with a median of 4.9]. No significant association was found between serum melatonin and ( MTNR1A) SNP (rs13140012) (p = 0.633).

          Conclusion

          These results lead us to suggest that melatonin production is impaired in ESRD patients (included in this pilot study), and this impairment is more evident in atherosclerotic ESRD patients.

          Abstract

          Health sciences; Renal system; Internal medicine; Endocrinology; Clinical research; Diagnostics; Melatonin; Single nucleotide polymorphism (SNP); rs13140012; Atherosclerosis; End-stage renal disease (ESRD); Hemodialysis (HD); Carotid intima-media thickness (CIMT)

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          Melatonin as a natural ally against oxidative stress: a physicochemical examination.

          Annia Galano, Dun Tan, Russel Reiter (2011)
          Oxidative stress has been proven to be related to the onset of a large number of health disorders. This chemical stress is triggered by an excess of free radicals, which are generated in cells because of a wide variety of exogenous and endogenous processes. Therefore, finding strategies for efficiently detoxifying free radicals has become a subject of a great interest, from both an academic and practical points of view. Melatonin is a ubiquitous and versatile molecule that exhibits most of the desirable characteristics of a good antioxidant. The amount of data gathered so far regarding the protective action of melatonin against oxidative stress is overwhelming. However, rather little is known concerning the chemical mechanisms involved in this activity. This review summarizes the current progress in understanding the physicochemical insights related to the free radical-scavenging activity of melatonin. Thus far, there is a general agreement that electron transfer and hydrogen transfer are the main mechanisms involved in the reactions of melatonin with free radicals. However, the relative importance of other mechanisms is also analyzed. The chemical nature of the reacting free radical also has an influence on the relative importance of the different mechanisms of these reactions. Therefore, this point has also been discussed in detail in the current review. Based on the available data, it is concluded that melatonin efficiently protects against oxidative stress by a variety of mechanisms. Moreover, it is proposed that even though it has been referred to as the chemical expression of darkness, perhaps it could also be referred to as the chemical light of health. © 2011 John Wiley & Sons A/S.
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            Melatonin: Physiological effects in humans.

            B Claustrat, J Leston (2015)
            Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland at night under normal light/dark conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained to the light/dark cycle. Light is able to either suppress or synchronize melatonin production according to the light schedule. The nycthohemeral rhythm of this hormone can be evaluated by repeated measurement of plasma or saliva melatonin or urine sulfatoxymelatonin, the main hepatic metabolite. The primary physiological function of melatonin, whose secretion adjusts to night length, is to convey information concerning the daily cycle of light and darkness to body structures. This information is used for the organisation of functions, which respond to changes in the photoperiod such as the seasonal rhythms. Seasonal rhythmicity of physiological functions in humans related to possible alteration of the melatonin message remains, however, of limited evidence in temperate areas under field conditions. Also, the daily melatonin secretion, which is a very robust biochemical signal of night, can be used for the organisation of circadian rhythms. Although functions of this hormone in humans are mainly based on correlations between clinical observations and melatonin secretion, there is some evidence that melatonin stabilises and strengthens coupling of circadian rhythms, especially of core temperature and sleep-wake rhythms. The circadian organisation of other physiological functions depend also on the melatonin signal, for instance immune, antioxidant defences, haemostasis and glucose regulation. The difference between physiological and pharmacological effects of melatonin is not always clear but is based upon consideration of dose and not of duration of the hormone message. It is admitted that a "physiological" dose provides plasma melatonin levels in the same order of magnitude as a nocturnal peak. Since the regulating system of melatonin secretion is complex, following central and autonomic pathways, there are many pathophysiological situations where melatonin secretion can be disturbed. The resulting alteration could increase the predisposition to disease, add to the severity of symptoms or modify the course and outcome of the disorder. Since melatonin receptors display a very wide distribution in the body, putative therapeutic indications of this compound are multiple. Great advances in this field could be achieved by developing multicentre trials in a large series of patients, in order to establish efficacy of melatonin and absence of long-term toxicity.
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              Pathophysiology and treatment of atherosclerosis

              S. Bergheanu, M. Bodde, J. Jukema (2017)
              Recent years have brought a significant amount of new results in the field of atherosclerosis. A better understanding of the role of different lipoprotein particles in the formation of atherosclerotic plaques is now possible. Recent cardiovascular clinical trials have also shed more light upon the efficacy and safety of novel compounds targeting the main pathways of atherosclerosis and its cardiovascular complications. In this review, we first provide a background consisting of the current understanding of the pathophysiology and treatment of atherosclerotic disease, followed by our future perspectives on several novel classes of drugs that target atherosclerosis. The focus of this update is on the pathophysiology and medical interventions of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and lipoprotein(a) (Lp(a)).
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                Author and article information

                Contributors
                Mohamed Hesham El Nashar
                Journal
                Journal ID (nlm-ta): Heliyon
                Journal ID (iso-abbrev): Heliyon
                Title: Heliyon
                Publisher: Elsevier
                ISSN (Electronic): 2405-8440
                Publication date PMC-release: 11 July 2020
                Publication date Collection: July 2020
                Publication date (Electronic): 11 July 2020
                Volume: 6
                Issue: 7
                Electronic Location Identifier: e04394
                Affiliations
                [a ]Department of Internal Medicine, Endocrinology Unit, Faculty of Medicine, University of Alexandria, Egypt
                [b ]Department of Clinical and Chemical Pathology, Faculty of Medicine, University of Alexandria, Egypt
                [c ]Department of Internal Medicine, Nephrology Unit, Faculty of Medicine, University of Alexandria, Egypt
                [d ]Department of Nephrology, Gamal Abd El Nasser Hospital, General Authority for Health Insurance, Alexandria Branch, Egypt
                Author notes
                [∗ ]Corresponding author. ehesho@ 123456me.com
                Article
                Publisher ID: S2405-8440(20)31238-X Publisher ID: e04394
                DOI: 10.1016/j.heliyon.2020.e04394
                PMC ID: 7358736
                SO-VID: ad372843-caf0-4285-9109-2a091fa30dd3
                Copyright © © 2020 The Author(s)
                License:

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 5 January 2020
                Date revision received : 20 May 2020
                Date accepted : 1 July 2020
                Categories
                Subject: Article

                Keywords: health sciences,renal system,internal medicine,endocrinology,clinical research,diagnostics,melatonin,single nucleotide polymorphism (snp),rs13140012,atherosclerosis,end-stage renal disease (esrd),hemodialysis (hd),carotid intima-media thickness (cimt)
                Data availability:
                Keywords: health sciences, renal system, internal medicine, endocrinology, clinical research, diagnostics, melatonin, single nucleotide polymorphism (snp), rs13140012, atherosclerosis, end-stage renal disease (esrd), hemodialysis (hd), carotid intima-media thickness (cimt)

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