Etudes sur les hormones

Actions santé de la mélatonine

11/01/2019 | Etudes sur les hormones et Echauffement et blessures et Etudes Compléments alimentaires et Etudes Anti-âge

 

The multiple protective roles and molecular mechanisms of melatonin and its precursor N-acetylserotonin in targeting brain injury and liver damage and in maintaining bone health
ChengliangLuoa       Free Radical Biology and Medicine Volume 130, January 2019, Pages 215-233

Highlights
• Melatonin and NAS are protective agents for brain injury, liver damage and bone health.
• Melatonin and NAS are anti-oxidative stress and anti-inflammation.
• Melatonin and NAS are against autophagy dysfunction and anti-apoptosis.
• MT1/MT2 are needed for brain and liver injuries and MT2 is important for bone health.
• Melatonin and NAS will be likely to show utility in clinical trials.

Melatonin is a neurohormone associated with sleep and wakefulness and is mainly produced by the pineal gland. Numerous physiological functions of melatonin have been demonstrated including anti-inflammation, suppressing neoplastic growth, circadian and endocrine rhythm regulation, and its potent antioxidant activity as well as its role in regeneration of various tissues including the nervous system, liver, bone, kidney, bladder, skin, and muscle, among others.

In this review, we summarize the recent advances related to the multiple protective roles of melatonin receptor agonists, melatonin and N-acetylserotonin (NAS), in brain injury, liver damage, and bone health. Brain injury, including traumatic brain injury, ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and newborn perinatal hypoxia-ischemia encephalopathy, is a major cause of mortality and disability. Liver disease causes serious public health problems and various factors including alcohol, chemical pollutants, and drugs induce hepatic damage. Osteoporosis is the most common bone disease in humans. Due in part to an aging population, both the cost of care of fracture patients and the annual fracture rate have increased steadily. Despite the discrepancy in the pathophysiological processes of these disorders, time frames and severity, they may share several common molecular mechanisms. Oxidative stress is considered to be a critical factor in these pathogeneses. We update the current state of knowledge related to the molecular processes, mainly including anti-oxidative stress, anti-apoptosis, autophagy dysfunction, and anti-inflammation as well as other properties of melatonin and NAS. Particularly, the abilities of melatonin and NAS to directly scavenge oxygen-centered radicals and toxic reactive oxygen species, and indirectly act through antioxidant enzymes are disscussed. In this review, we summarize the similarities and differences in the protection provided by melatonin and/or NAS in brain, liver and bone damage.

We analyze the involvement of melatonin receptor 1A (MT1), melatonin receptor 1B (MT2), and melatonin receptor 1C (MT3) in the protection of melatonin and/or NAS. Additionally, we evaluate their potential clinical applications. The multiple mechanisms of action and multiple organ-targeted properties of melatonin and NAS may contribute to development of promising therapies for clinical trials.

Combien de mélatonine pour la santé?

26/12/2018 | Etudes sur les hormones et Etudes Compléments alimentaires et Etudes Anti-âge

 

Melatonin as a chronobiotic/cytoprotector: its role in healthy aging
Daniel P. Cardinali         Biological Rhythm Research Volume 50, 2019 - Issue 1

Preservation of sleep, a proper nutrition and adequate physical exercise are key elements for healthy aging. Aging causes sleep alterations, and in turn, sleep disturbances lead to numerous pathophysiological changes that accelerates the aging process. In the central nervous system, sleep loss impairs the clearance of waste molecules like amyloid-β or tau peptides. Melatonin, a molecule of unusual phylogenetic conservation present in all known aerobic organisms, is effective both as a chronobiotic and a cytoprotective agent to maintain a healthy aging.

The late afternoon increase of melatonin “opens the sleep doors” every night and its therapeutic use to preserve slow wave sleep has been demonstrated. Melatonin reverses inflammaging via prevention of insulin resistance, suppression of inflammation and down regulation of proinflammatory cytokines. Melatonin increases the expression of α- and γ-secretase and decreases β-secretase expression. It also inhibits tau phosphorylation. Clinical data support the efficacy of melatonin to treat Alzheimer’s disease, particularly at the early stages of disease. From animal studies the cytoprotective effects of melatonin need high doses to become apparent (i.e. in the 40–100 mg/day range). The potentiality of melatonin as a nutraceutical is discussed.

De la carnosine pour la régénération nerveuse?

07/12/2018 | Etudes sur les hormones et Echauffement et blessures et Etudes Compléments alimentaires et Etudes Anti-âge

 

Carnosine improves functional recovery and structural regeneration after sciatic nerve crush injury in rats
Navideh Mirzakhani             Life Sciences volume 215, 15 December 2018, Pages 22-30


Aims
Peripheral nerve injury represents a substantial clinical problem with insufficient or unsatisfactory treatment options. Current researches have extensively focused on the new approaches for the treatment of peripheral nerve injuries. Carnosine is a naturally occurring pleotropic dipeptide and has many biological functions such as antioxidant property. In the present study, we examined the regenerative ability of carnosine after sciatic nerve crush injury using behavioral, biochemical, histological and ultrastructural evaluations.

Materials and methods
Seventy-two rats were divided into six groups including control, sham, crush and carnosine (10, 20 and 40 mg/kg) groups. Crush injury in left sciatic nerve was induced by a small haemostatic forceps. Carnosine was administered for 15 consecutive days after induction of crush injury. Sciatic functional index (SFI) was recorded weekly. Histopathological and ultrastructural evaluations were made using light and electron microscopes, respectively. Sciatic nerve tissue malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-alpha (TNF-α) levels were measured. Gastrocnemius muscle weight was determined.

Key findings
Carnosine at the doses of 20 and 40 mg/kg accelerated SFI recovery. Wallerian degeneration severity and myelinated fibers density, myelin sheath thickness and diameter as well as ultrastructural changes of myelinated axons were improved. It also recovered nerve tissue biochemical (MDA, SOD and TNF-α) changes induced by crush injury. Muscle weight ratio was reached to near normal values.

Our results suggest a regenerative effect of carnosine. Inhibition of oxidative stress and inflammatory pathways, along with provocation of myelination and prevention of muscular atrophy might be involved in this effect of carnosine.

Significance
Carnosine treatment might be considered as a therapeutic agent for peripheral nerve regeneration and its functional recovery.

Utilisation de plaquettes contre les blessures

25/10/2018 | Etudes sur les hormones et Echauffement et blessures

 

Platelet releasate promotes skeletal myogenesis by increasing muscle stem cell commitment to differentiation and accelerates muscle regeneration following acute injury
David Scully Acta Physiol : 19 October 2018

Aim
The use of platelets as biomaterials has gained intense research interest. However, the mechanisms regarding platelet‐mediated skeletal myogenesis remain to be established. The aim of this study was to determine the role of platelet releasate in skeletal myogenesis and muscle stem cell fate in vitro and ex vivo respectively.

Methods
We analysed the effect of platelet releasate on proliferation and differentiation of C2C12 myoblasts by means of cell proliferation assays, immunohistochemistry, gene expression and cell bioenergetics. We expanded in vitro findings on single muscle fibres by determining the effect of platelet releasate on murine skeletal muscle stem cells using protein expression profiles for key myogenic regulatory factors.

Results
TRAP6 and collagen used for releasate preparation had a more pronounced effect on myoblast proliferation versus thrombin and sonicated platelets (P<0.05). In addition, platelet concentration positively correlated with myoblast proliferation. Platelet releasate increased myoblast and muscle stem cell proliferation in a dose‐dependent manner, which was mitigated by VEGFR and PDGFR inhibition. Inhibition of VEGFR and PDGFR ablated MyoD expression on proliferating muscle stem cells, compromising their commitment to differentiation in muscle fibres (P<0.001). Platelet releasate was detrimental for myoblast fusion and affected differentiation of myoblasts in a temporal manner. Most importantly we show that platelet releasate promotes skeletal myogenesis through the PDGF/VEGF‐Cyclin D1‐MyoD‐Scrib‐Myogenin axis and accelerates skeletal muscle regeneration after acute injury.

Conclusion
This study provides novel mechanistic insights on the role of platelet releasate in skeletal myogenesis and set the physiological basis for exploiting platelets as biomaterials in regenerative medicine.

Irisine: le lien entre la muscu et le renforcement osseux?

14/03/2018 | Etudes sur les hormones et Etudes Perte de poids et Etudes Anti-âge

 

Myokine—Irisin—and Its Effects Linking Bone and Muscle Function
Graziana Colaianni           Clinical Reviews in Bone and Mineral Metabolism March 2018, Volume 16, Issue 1, pp 16–21

Irisin is a myokine secreted by the skeletal muscle during physical activity both in mice and humans. Its first identified role was to activate the browning response in white adipocytes, subsequently triggering non-shivering thermogenesis; therefore, Irisin has raised great expectations as a potential target in the treatment of obesity. In 2015, we demonstrated that Irisin plays a central role in the control of bone mass, driving positive effects on cortical mineral density and bone mechanical properties. This effect on the bone was triggered using an Irisin dosage 70 times lower than the one needed to induce the browning response, suggesting that the skeleton is the primary target organ of this myokine. Moreover, our studies also highlighted the autocrine effect of Irisin on the skeletal muscle, overall suggesting that Irisin plays a fundamental role in the physiology of the musculoskeletal system. More recently, we demonstrated the efficacy of Irisin in preventing and restoring bone and muscle losses in a mouse model affected by disuse-induced osteoporosis and muscular atrophy. Hopefully, if future investigations will be confirmed in humans, it may lead to develop an Irisin-based therapy for physically disable or bedridden patients and it might also represent a countermeasure for astronauts subjected to microgravity.

Deca dick?

14/02/2018 | Etudes sur les hormones et Etudes Anti-âge

 

Nandrolone combined with strenuous resistance training reduces vascular nitric oxide bioavailability and impairs endothelium-dependent vasodilation
Steroids Volume 131, March 2018, Pages 7-13     ViniciusGuzzoni

Highlights
• Nandrolone plus strenuous RT impairs acetylcholine-mediated aorta vasodilation.
• Nandrolone plus strenuous RT increased reactive species of oxygen levels.
• Nandrolone plus strenuous RT dramatically reduced vascular NO bioavailability.
• Nandrolone plus strenuous RT increased arterial wall thickness.
• Combination of nandrolone and strenuous RT might lead endothelial dysfunction.

Anabolic Androgenic Steroids (AASs) misuse has increased among adolescents and recreational athletes due to their potential effects on muscle hypertrophy. On the other hand, AAS might induce alterations on cardiovascular system, although some controversies regarding AAS on vascular properties remain unknown. To address this question, we aimed to investigate the effects of high doses of nandrolone combined with strenuous resistance training (RT) on function and structure of thoracic aorta. Rats were randomized into four groups: non-trained vehicle (NTV), trained vehicle (TV), non-trained nandrolone (NTN), and trained nandrolone (TN), and submitted to 6 weeks of treatment with nandrolone (5 mg/kg, twice a week) and/or resistance training. In vitro response of thoracic aorta to acetylcholine (ACh) was analyzed. Vascular nitric oxide (NO) and reactive oxygen species (ROS) synthesis were evaluated using 4,5-diaminofluorescein diacetate (DAF-2) and hydroethidine fluorescent techniques, respectively. Thoracic aorta was processed for microscopy analyses and tunica media thickness was measured. ACh-mediated relaxation response was impaired in endothelium intact aortic rings isolated from trained rats (TV and TN) as compared with their matched non-trained groups. TN rats showed reduced ACh-mediated vasodilatation than NTN rats. NO production and bioavailability decreased in thoracic aorta of nandrolone-treated rats in relation to their matched non-trained group (NTN vs. NTV; TN vs. TV). ROS production and tunica media thickness were increased in TN rats when compared with TV rats.

These findings indicate that high doses of nandrolone combined with strenuous RT affect NO bioavailability and might induce endothelial dysfunction and arterial morphological alterations.

Rôle des recepteurs aux androgènes sur la masse grasse

02/02/2018 | Etudes sur les hormones et Etudes Perte de poids

 

The androgen receptor in bone marrow progenitor cells negatively regulates fat mass
Patricia K Russell J Endo 2018

It is well established that testosterone negatively regulates fat mass in humans and mice, however the mechanism by which testosterone exerts these effects is poorly understood. We and others have shown that deletion of the androgen receptor (AR) in male mice results in a phenotype that mimics the three key clinical aspects of hypogonadism in human males; increased fat mass, and decreased bone and muscle mass. We now show that replacement of the AR gene specifically in mesenchymal progenitor cells (PCs) residing in the bone marrow of Global-ARKO mice, in the absence of the AR in all other tissues (PC-AR Gene Replacements), completely attenuates their increased fat accumulation. Inguinal subcutaneous white adipose tissue and intra-abdominal retroperitoneal visceral adipose tissue depots in PC-AR Gene Replacement mice were 50-80% lower than wild type (WT) and 75-90% lower than Global-ARKO controls at 12 weeks of age. The marked decrease in subcutaneous and viceral fat mass in PC-AR Gene Replacements was associated with an increase in the number of small adipocytes and a healthier metabolic profile compared to WT controls, characterised by normal serum leptin and elevated serum adiponectin levels. Euglycaemic/hyperinsulinaemic clamp studies reveal that the PC-AR Gene replacement mice have improved whole-body insulin sensitivity with higher glucose infusion rates compared to WT mice and increased glucose uptake into subcutaneous and intra-abdominal fat.

In conclusion, these data provide the first evidence for an action of androgens via the AR in mesenchymal bone marrow PCs to negatively regulate fat mass and improve metabolic function.

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