
Jose Cipolla-NetoUniversity of São Paulo | USP · Instituto de Ciências Biomédicas (ICB)
Jose Cipolla-Neto
MD, PhD, Full Professor
Melatonin physiology and the consequent pathophysiology of its dysfunction, both in experimental and clinical studies
About
246
Publications
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Introduction
Additional affiliations
Education
March 1972 - April 1978
Institute of Biomedical Sciences, University of São Paulo
Field of study
- Physiology
February 1964 - July 1971
Faculty of Medicine- University of São Paulo
Field of study
- Medicine
Publications
Publications (246)
Shift work was recently described as a factor that increases the risk of Type 2 diabetes mellitus. In addition, rats born to mothers subjected to a phase shift throughout pregnancy are glucose intolerant. However, the mechanism by which a phase shift transmits metabolic information to the offspring has not been determined. Among several endocrine s...
Melatonin is an old and ubiquitous molecule in nature showing multiple mechanisms of action and functions in practically every living organism. In mammals, pineal melatonin function as a hormone and a chronobiotic, playing a major role in the regulation of the circadian temporal internal order. The anti-obesogen and the weight-reducing effects of m...
Melatonin is a neurohormone that works as a nighttime signal for circadian integrity and health maintenance. It is crucial for energy metabolism regulation and the diabetes effects on its synthesis are unresolved. Using diverse techniques that included pineal microdialysis and ultrahigh performance liquid chromatography, the present data show a cle...
Melatonin is a ubiquitous molecule present in almost every live being from bacteria to humans. In vertebrates, besides being produced in peripheral tissues and acting as an autocrine and paracrine signal, melatonin is centrally synthetized by a neuroendocrine organ, the pineal gland. Independently of the considered specie, pineal hormone melatonin...
Melatonin is a ubiquitous molecule in nature, being locally synthesized in several cells and tissues, besides being a hormone that is centrally produced in the pineal gland of vertebrates, particularly in mammals. Its pineal synthesis is timed by the suprachiasmatic nucleus, that is synchronized to the light-dark cycle via the retinohypothalamic tr...
The book “Noninvasive Methods in Cardiology 2024” include the results from close cooperation with Masaryk University and the university of Minnesota. The editors and authors present the results of chronobiology and variability of blood pressure in healthy subjects and patients with hypertension and ischemic coronary diseases, The results were prese...
Poor sleep quality is associated with unhealthy dietary choices and worse body composition among night-shift workers and women during the climacteric period. This study aimed to evaluate the effect of exogenous melatonin administration on the dietary intake and body composition in healthcare workers exposed to fixed-shift work during the climacteri...
Melatonin is a pineal hormone synthesized exclusively at night, in several organisms. Its action on sperm is of particular interest, since they transfer genetic and epigenetic information to the offspring, including microRNAs, configuring a mechanism of paternal epigenetic inheritance. MicroRNAs are known to participate in a wide variety of mechani...
Glaucoma is a chronic optic neuropathy characterized by the progressive degeneration of retinal ganglion cells (RGC). These cells play a crucial role in transmitting visual and non‐visual information to brain regions, including the suprachiasmatic nucleus (SCN), responsible for synchronizing biological rhythms. To understand how glaucoma affects ci...
Background
Ovarian cryopreservation is a promising technique despite being hindered by damage from freezing and thawing. Melatonin can mitigate this outcome.
Objective
This study aimed to evaluate the effect of melatonin on the follicular dynamics of ovarian tissue in a cryopreserved cell culture.
Methods
Three-month-old adult female Wistar rats...
Pineal melatonin participates in the control of numerous biological functions through its immediate effects, which result from its high presence in the systemic circulation during the dark phase of the circadian cycle or, through its prolonged effects, when its level is extremely low during the light phase. At pregnancy, maternal melatonin signals...
Background and objective
A single session of aerobic exercise lowers blood pressure (BP), known as postexercise hypotension (PEH). Bright light (BL) exposure increases BP at rest compared to dim light (DL). However, whether BL exposure can attenuate PEH remains unknown, and this hypothesis was tested in the current study.
Methods
Twenty healthy me...
Pineal melatonin participates in the control of numerous biological functions through its immediate effects, which result from its high presence in the systemic circulation during the dark phase of the circadian cycle or, through its prolonged effects, when its level is extremely low during the light phase. At pregnancy, maternal melatonin signals...
This study aimed to test whether bright light (BL) exposure attenuates the reduction in blood pressure (BP) postexercise compared to dim light (DL). Twenty healthy men (27 ± 5 years) randomly underwent two experimental sessions: one under BL (5000 lux) and another under dim light (DL <8lux). In each session, subjects executed a bout of aerobic exer...
Shiroma, M.E.; Damous, L.L.; Simões, M.d.J.; Simões, R.d.S.; Cipolla-Neto, J.; Baracat, E.C.; Soares-Jr., J.M. Antioxidant Actions of Melatonin: A Systematic Review of Animal Studies. Antioxidants 2024, 13, 439. https:// Abstract: Melatonin is an indoleamine with crucial antioxidant properties that are used to combat inflammatory and neoplastic pro...
Aim
The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to antioxidant pathways modulate susceptibility to these complications. Considering that melatonin is a powerful antioxidant compound, our aim was to explore, in a longitudinal cohor...
Introduction
Interactions between circadian clocks and key mediators of chronic low-grade inflammation associated with fat consumption may be important in maintaining metabolic homeostasis and may pose a risk for the development of obesity-associated comorbidities, especially type 2 diabetes (T2DM).
Objective
The aims of the present study were to...
The book “Noninvasive Methods in Cardiology 2024” include the results from close cooperation with Masaryk University and the university of Minnesota. The editors and authors present the results of chronobiology and variability of blood pressure in healthy subjects and patients with hypertension and ischemic coronary diseases, The results were prese...
The molecular circadian timing system involves genes known as "clock genes," such as the PER3 gene. Studies have demonstrated associations among a repeat polymorphism (VNTR) of the PER3 gene with chronotypes, with the occurrence of circadian rhythm disorders and with sleep home-ostasis phenotypes. The aim of this study was to investigate, by actigr...
Melatonin concentration is several folds higher in the follicular fluid than that in blood suggesting an important role of this molecule on follicular physiology. However, the actions of melatonin on angiogenesis in granulosa cells are currently unknown. In this study, we have specifically investigated the potential effects of melatonin on the angi...
This review presents the main metrics developed so far to correlate physical properties of light and its effects on melatonin suppression. Melatonin is a hormone secreted at night and its production is suppressed by exposure to light. In this context, the negative effects of lighting at night and high exposure to light raise the need for a better q...
Unlabelled:
Suppressive therapy of recurrent genital herpes is a challenge, and melatonin may be an alternative.
Objective:
To evaluate the action of melatonin, acyclovir, or the association of melatonin with acyclovir as a suppressive treatment in women with recurrent genital herpes.
Design:
The study was prospective, double-blind, and random...
This study investigated the seasonal variations in mRNA expression of FSH (Fshr), LH (Lhr) receptors, melatonin (Mt1 and Mt2) receptors, melatonin-synthetizing enzymes (Asmt and Aanat) and melatonin concentration in developing follicles from mares raised in natural photoperiods. For one year, ultrasonographic follicular aspiration procedures were p...
Simple Summary: Reproductive activity in mares shows a seasonal pattern that is associated with an increasing photoperiod with a pronounced incidence of ovulations during spring and summer. The photoperiodic control of reproductive activity is mediated by melatonin, secreted by the pineal gland, which plays an inhibitory role in ovulatory activity...
Several psychosocial, sleep/circadian, and cardiometabolic disorders have intricately interconnected pathologies involving melatonin disruption. Therefore, we hypothesize that melatonin could be a therapeutic target for treating potential comorbid diseases associated with this triad of psychosocial-sleep/circadian-cardiometabolic disorders. We inve...
A large research portfolio indicates that an activated renal renin-angiotensin system or a deficit on melatonin is associated with several cardiovascular pathologies. In this observational clinical study, we hypothesized that alterations in urinary melatonin or angiotensinogen levels may be altered in two common conditions, preeclampsia and gestati...
Melatonin may have a role in the pathophysiology of a set of three diseases categories that interact with each other, namely psychosocial stress disorders, sleep/circadian rhythm disturbances, and cardiometabolic diseases, forming a therapeutic target triad for melatonin (stress-sleep/circadian- cardiometabolic disorders triad). Establishing a rela...
Pineal gland secretes the hormone melatonin at night with a circadian rhythm. The synthesis and secretion of melatonin are stimulated at night by norepinephrine released by sympathetic postganglionic neurons projecting from the superior cervical ganglia. Norepinephrine simultaneously activates α- and β-adrenoceptors, triggering melatonin synthesis....
Melatonin is synthesized and secreted by the pineal gland in mammals. Its synthesis is triggered at night by norepinephrine released in the interstices of the gland. This nocturnal production is dependent on the transcription, translation, and/or activation of the enzymes arylalkylamine-N-acetyltransferase (AANAT), acetylserotonin O-methyltransfera...
The pinealectomy technique consists of the surgical removal of the superficial pineal gland. This procedure allows the ablation of circulating indoles produced by this gland. Withdrawal of systemic melatonin, a pineal hormone, affects animal circadian rhythms and induces several physiological changes that are the subject of many investigations. In...
Mammalian pineal glands are composed mostly of pinealocytes, which are the melatonin secretory cells, and also importantly of glial cells in special astrocytes. With the aim of studying the interactions between pinealocytes and astrocytes, the methodologies for obtaining and maintaining isolated pinealocytes and astrocytes in culture were standardi...
Pineal microdialysis is characterized by the real-time monitoring of melatonin, neurotransmitters, metabolites, and other compounds released by the pineal gland throughout 24 h. It is a technique with great advantages that allows in vivo study of the ongoing pineal gland metabolism. In this chapter, we describe the entire process of pineal microdia...
Background and aims:
Melatonin is a pineal hormone that plays an important role as an endogenous synchronizer of circadian rhythms and energy metabolism. As this circadian component has been closely related to eating behavior, an important question on this topic would be whether melatonin administration could influence eating habits. However, this...
Studies have suggested that dietary composition and meal timing of night workers differs from day workers, and it may be associated with sleep disturbances. The aim of the present study was to assess the relationship of macronutrient intake and meal timing during work-days and days-off with objective and subjective parameters of sleep among overwei...
Melatonin, a phylogenic conserved molecule, presents in almost all living organisms and it is believed to be originated to protect the unicellular organisms from oxidative products which were emerged from aerobic respiration. Even with the acquisition of a variety of other functions along evolution, the crucial autocrine, paracrine and endocrine ac...
The effects of pinealectomy and melatonin replacement therapy on the mRNA expression of melatonin (Mt1, Mt2 and Rora), steroidogenic (Era - Estrogen a, Erb - Estrogen b, Ar - Androgen, Pgr - Progesterone, Lhr - LH and Oxr - Oxytocin receptors) -related receptors and melatonin-synthetic enzyme genes (Tph1, Asmt and Aanat) in oviduct and uterus of Wi...
Objective: To assess the adherence to a set of evidence-based recommendations to support mental health during the coronavirus disease 2019 (COVID-19) pandemic and its association with depressive and anxiety symptoms.
Methods: A team of health workers and researchers prepared the recommendations, formatted into three volumes (1: COVID-19 prevention;...
Objective: To assess the adherence to a set of evidence-based recommendations to support mental
health during the coronavirus disease 2019 (COVID-19) pandemic and its association with depressive
and anxiety symptoms.
Methods: A team of health workers and researchers prepared the recommendations, formatted into
three volumes (1: COVID-19 prevention;...
Background: A large research portfolio indicates that an activated renal renin-angiotensin system or a deficit on melatonin is associated with several cardiovascular pathologies. In this observational clinical study, we hypothesized that alterations in urinary melatonin or angiotensinogen levels may be altered in two common conditions, preeclampsia...
Diabetes mellitus (DM) leads to complications, the majority of which are nephropathy, retinopathy, and neuropathy. Redox imbalance and inflammation are important components of the pathophysiology of these complications. Many studies have been conducted to find a specific treatment for these neural complications, and some of them have investigated t...
Night workers tend to eat irregularly, both in terms of meal times and composition. The disruption in energy metabolism caused by inappropriate eating habits can negatively affect the sleep quality of these individuals. The objectives of this study were to determine the interval between the last meal and bedtime and its relationship with both diurn...
Nocturnal melatonin secretion is important for preservation of ß-cell mass and function. Knowing that type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia caused by the elevated resistance of peripheral tissues to insulin, reduction in pineal melatonin and disturbances of insulin secretion by pancreatic ß-c...
Melatonin, a hormone released by the pineal gland, demonstrates several effects on the cardiovascular system. Herein, we performed a systematic review and meta-analysis to verify the effects of melatonin in an experimental model of myocardial infarction. We performed a systematic review according to PRISMA recommendations and reviewed MEDLINE, Emba...
Shift workers experience chronic circadian misalignment, which can manifest itself in reduced melatonin production, and has been associated with metabolic disorders. In addition, chronotype modulates the effect of night shift work, with early types presenting greater circadian misalignment when working night shift as compared to late types. Melaton...
Night work can lead to social jetlag (SJL), which can be briefly defined as the difference between social and biological time. In this sense, SJL has been viewed as a proxy for circadian misalignment. Studies have suggested that SJL may modify physiological processes, such as blood pressure, glucose metabolism, cortisol, and melatonin production. T...
Melatonin, an indolamine mainly released from the pineal gland, is associated with many biological functions namely the modulation of circadian and seasonal rhythms, sleep inducer, regulator of energy metabolism, antioxidant and anticarcinogenic. Although several evidences also recognize the influence of melatonin in the reproductive physiology, th...
Backgroud
Melatonin has anti-inflammatory and antioxidative actions at the mitochondrial level. This indole-containing molecule may protect ovarian grafts during the process of cryopreservation. Therefore, we aimed to determine whether melatonin pretreatment improves rat ovarian graft quality.
Methods
Twenty-six female rats were allocated to two s...
The endocrine pancreas of pregnant rats shows evident plasticity, which allows the morphological structures to return to the nonpregnant state right after delivery. Furthermore, it is well‐known the role of melatonin in the maintenance of the endocrine pancreas and its trophism. Studies indicate increasing nocturnal serum concentrations of maternal...
The pineal gland synthesizes melatonin exclusively at night, which gives melatonin the characteristic of a temporal synchronizer of the physiological systems. Melatonin is a regulator of insulin activities centrally and also peripherally and its synthesis is reduced in diabetes. Since monosodium glutamate (MSG) is often used to induce the type 2 di...
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Aims: Investigate the role of melatonin on the regulation of body temperature in aged animals that have impaired melaton...
Objective
To evaluate the relationship between proxy for circadian disruption, eating habits, sleep characteristics and dyslipidemic parameters.
Methods
This is a randomized, double-blind, crossover controlled clinical trial, and for this study, only baseline data were used. The sample was composed of 36 overweight female nurses who worked on a fi...
Objective:
The aim of this study was to evaluate the relationship between proxy for circadian disruption, eating habits, sleep characteristics, and dyslipidemic parameters.
Methods:
This was a randomized, double-blind, crossover controlled clinical trial, and for this study, only baseline data were used. The sample was composed of 36 overweight...
Despite the evolving advances in clinical approaches to obesity and its inherent comorbidities, the therapeutic challenge persists. Among several pharmacological tools already investigated, recent studies suggest that melatonin supplementation could be an efficient therapeutic approach in the context of obesity. In the present review, we have amalg...
Background: Melatonin has anti-inflammatory and antioxidative actions at the mitochondrial level. This indole may protect the ovarian graft during the cryopreservation process. Therefore, our study aimed to determine whether melatonin pretreatment improves rat ovarian graft quality.
Methods: Twenty female rats were allocated to two study groups of...
This study investigated the effects of melatonin supplementation on the daily mRNA expression of Bmp-15, Gdf-9, FSH (Fshr) and LH (Lhr) receptor genes and the effect of gonadotropin supplementation on protein expression of melatonin-synthetizing enzymes (ASMT and AANAT) during in vitro maturation (IMV) of rat follicle-enclosed oocytes. We also stud...
Objective:
Melatonin has been shown to increase brown adipose tissue (BAT) mass, which can lead to important metabolic effects, such as bodyweight reduction and glycemic improvement. However, BAT mass can only be measured invasively and. The gold standard for non-invasive measurement of BAT activity is positron emission tomography with 2-deoxy-2-[...