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1.
Braz. j. biol ; 84: e253061, 2024. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1364520

ABSTRACT

Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.


A fibrose hepática é a fase inicial de qualquer doença hepática crônica, e em sua fase final desenvolve-se para cirrose. As doenças hepáticas crônicas são uma questão de saúde global crucial e a causa de aproximadamente 2 milhões de mortes por ano em todo o mundo. A cirrose, hoje em dia, é a 11ª causa mais comum de morte globalmente. O tratamento da célula-tronco mesenquimal (MSCs) é uma maneira eletiva de tratar a doença hepática aguda e crônica. O objetivo deste estudo é melhorar o potencial terapêutico dos MSCs combinados com a melatonina (MLT) para superar a fibrose hepática induzida por CCl4 e também investigar o impacto individual da melatonina e MSCs contra o comprometimento do fígado induzido por CCl4 no modelo animal. Os ratos BALB / C fêmeas foram usados ​​como modelo de animal fibrótico de fígado induzido por CCl4. Cinco grupos de modelo animal foram feitos: Controle Negativo, Controle Positivo, CCl4 + MSCs Tratados Grupo, Grupo Tratado CCl4 + MLT e Grupo Tratado CCl4 + MSCs + MLT. MSCs cultivados da medula óssea dos ratos foram transplantados para o modelo de camundongos de fígado induzido por CCl4, individualmente, bem como em conjunto com a melatonina. Duas semanas após a administração MSCs e MLT, todos os grupos de camundongos foram sacrificados para o exame. Os resultados morfológicos e histopatológicos mostraram que a terapia combinada do MSCs + MLT mostrou impacto benéfico substancial no modelo ferido no fígado induzido pelo CCl4, em comparação com o MSCs e o MLT individualmente. A redução bioquimicamente considerável foi observada em bilirrubina sérica e níveis ALT de ratinhos tratados com MLT + MSCs, em comparação com outros grupos. Os resultados de PCR mostraram regulação negativa do BAX e regulação positiva do BCL-XL e da albumina, confirmando um efeito terapêutico significativo do MSCs + MLT na fibrose hepática induzida por CCl4. Dos resultados, conclui-se que a terapia combinada de MSCs e MLT mostram um forte efeito terapêutico na fibrose hepática induzida por CCl4, em comparação com MSCs e MLT individualmente.


Subject(s)
Rats , Stem Cells , Fibrosis , Liver , Liver Diseases , Melatonin
2.
Medwave ; 22(8): e2568, 30/09/2022.
Article in English, Spanish | LILACS-Express | LILACS | ID: biblio-1396262

ABSTRACT

Introducción La encefalopatía hipóxico-isquémica neonatal es una patología caracterizada por una disfunción neurológica aguda, de severidad variable, causada por un episodio asfíctico perinatal. Se presenta en uno a seis de cada 1000 recién nacidos de término, asociándose a una alta morbimortalidad neonatal y a desenlaces neurológicos adversos. El uso de hipotermia es considerado como la terapia estándar para esta condición. Sin embargo, debido a su limitada eficacia clínica, se han propuesto diferentes opciones terapéuticas adyuvantes, incluyendo el uso de fármacos como la melatonina. Existe controversia sobre si la terapia combinada con melatonina es superior a la monoterapia con hipotermia. Métodos Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta-análisis y preparamos una tabla de resumen de los resultados utilizando el método Grading of Recommendations Assessment, Development and Evaluation, GRADE Resultados Identificamos dos revisiones sistemáticas que en conjunto incluyeron dos estudios primarios, ambos ensayos aleatorizados. Se incluyeron los dos ensayos aleatorizados en el análisis del presente trabajo. Conclusiones No es posible establecer con claridad si la adición de melatonina disminuye la mortalidad o la probabilidad de presentar alteraciones reflejadas en la resonancia magnética cerebral, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja. Por otro lado, adicionar melatonina a la terapia con hipotermia, comparado con la monoterapia con hipotermia, podría aumentar la probabilidad de que el examen neurológico sea normal a los seis meses, y que la cognición sea normal a los 18 meses. Finalmente, la adición de melatonina a la terapia con hipotermia probablemente disminuya la probabilidad de presentar convulsiones.


Introduction Neonatal hypoxic-ischemic encephalopathy is caused by perinatal asphyxia, resulting in an acute neurological dysfunction of variable severity. It occurs in one to six of every 1000 full-term newborns and is associated with high neonatal morbimortality and adverse neurological outcomes. The use of hypothermia is considered the standard therapy for this condition. However, different adjuvant therapeutic options have been proposed due to limited clinical efficacy, including drugs like melatonin. There is controversy about whether combined therapy with melatonin is superior to monotherapy with hypothermia. Methods We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, and Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of the findings table using the GRADE approach. Results We identified two systematic reviews that included two primary studies, both randomized trials. The two randomized trials were included in the analysis of the present work. Conclusion It is not possible to establish whether the addition of melatonin decreases mortality or the probability of alterations in brain magnetic resonance imaging because the certainty of the existing evidence has been assessed as very low. On the other hand, the addition of melatonin to hypothermia therapy, compared to hypothermia monotherapy, may increase the probability of normal neurological examination at six months and the probability of normal cognition at 18 months. Finally, adding melatonin to hypothermia therapy likely reduces the probability of seizures.

3.
Acta odontol. latinoam ; 35(2): 90-97, Sept. 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1403029

ABSTRACT

ABSTRACT Melatonin (MLT) is a hormone responsible for regulating several physiological processes. It has been shown that MLT can be an important mediator in bone formation and stimulation, promoting osteoblast differentiation. In clinical practice, in tissue regeneration procedures, it is necessary to use membranes or barriers, associated with biomaterials, or not. The aim of this in vitro study was to assess the effect of melatonin on the activity of osteoblastic cells, associated, or not, with a resorbable collagen membrane (Bio-Gideä). For this, mice-derived pre-osteoblastic cells MC3T3 obtained from the ATCC (American Type Culture Collection) were used. Cultured cells were subject to the following treatments: MLT with a concentration of 1mM, a Bio-Gideä membrane and a membrane associated with MLT (Bio-Gideä + MLT). Proliferation and cell viability assays and protein lysate (ELISA test) quantification for the BMP-2 protein were carried out, in periods of 72 hours, 7 days and 10 days. After analyzing the data (one-way ANOVA, alpha=5%) it was observed that when MLT was used in isolation, there was an increase in cell proliferation and viability in osteoblastic cells (p<0.05). But, when MLT was associated with resorbable membranes, there was an inverse behavior, both in terms of proliferation and viability (p<0.05). In the case of the ELISA test, no secretion of BMP-2 was detected in any of the analyzed groups. It is concluded that MLT has a stimulatory effect on osteoblasts, but, when associated with Bio-Gideä resorbable membranes, it does not show any viable action in osteoblastic cell stimulation.


RESUMO A melatonina (MLT) é um hormônio responsável pela regulação de diversos processos fisiológicos no nosso organismo. Tem sido demonstrado que a melatonina possa ser um importante mediador na formação e estimulação óssea, promovendo a diferenciação dos osteoblastos. Clinicamente, para o procedimento de regeneração tecidual, faz-se necessário a utilização de membranas ou barreiras, associadas ou não a biomateriais. Assim, o objetivo deste estudo in vitro foi avaliar o efeito da melatonina na atividade de células osteoblásticas, associada ou não a uma membrana de colágeno reabsorvível (Bio-Gide®). Para isto foram utilizadas células pré-osteoblásticas MC3T3 do ATCC (American Type Culture Collection), de camundongos. As células em cultura foram submetidas aos seguintes tratamentos: MLT na concentração de 1mM, membrana Bio Gide® e membrana associada à MLT (Bio-Gide® + MLT). Foram realizados os ensaios de proliferação e viabilidade celular e quantificação do lisado proteico (teste ELISA), para a proteína BMP-2, nos períodos de 72 horas, 7 e 10 dias. Após a análise dos dados (ANOVA um critério, alfa=5%) pode-se observar que a MLT quando utilizada sozinha, resultou em um aumento na proliferação e viabilidade celular nas células osteoblásticas (p<0,05). Entretanto, quando a MLT foi associada à membrana reabsorvível foi observado um comportamento inverso, tanto na proliferação quanto na viabilidade (p<0,05). Para o teste ELISA realizado, não houve secreção detectável de BMP-2 para nenhum grupo analisado. Conclui-se que a melatonina possui uma ação estimuladora nos osteoblastos, mas quando associada à membrana reabsorvível Bio-Gide®, não demonstra uma ação viável na estimulação de células osteoblásticas.

4.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 44(3): 342-348, May-June 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1374615

ABSTRACT

Objective: The prevalence of sleep disorders during the perinatal period is high and large health administrative database surveys have shown that the use of exogenous melatonin in pregnant populations is quite common, about 4%. Much of the concern about using melatonin during pregnancy and breastfeeding stems from animal research. Thus, the objective of this article is to provide a critical review of human studies related to exogenous melatonin use during pregnancy and breastfeeding. Methods: The electronic databases Ovid, MEDLINE, Embase, and the Cochrane Library were searched using terms and keywords related to melatonin, pregnancy, and breastfeeding. Results: Fifteen studies were included in this review. Eight focused on melatonin use during pregnancy and seven focused on melatonin use during breastfeeding. There was a variety of study designs, including case reports, cohort studies, and clinical trials. There is a lack of randomized, controlled trials examining the efficacy and safety of melatonin as a treatment for sleep disorders during pregnancy or breastfeeding and, notably, insomnia was not the primary outcome measure in any of the studies included in this review. Clinical trials that used exogenous melatonin during pregnancy and breastfeeding for other clinical conditions have not suggested major safety concerns or adverse events. Conclusion: Contrary to what animal studies have suggested, evidence from clinical studies to date suggests that melatonin use during pregnancy and breastfeeding is probably safe in humans. This review further emphasizes the need for clinical studies on sleep disorders, including exogenous melatonin, during pregnancy and lactation.

5.
Article in Chinese | WPRIM | ID: wpr-933333

ABSTRACT

Objective:To evaluate the effect of melatonin preconditioning on hepatic ischemia-reperfusion (I/R) injury in rats with non-alcoholic fatty liver disease (NAFLD).Methods:Forty-eight SPF male Sprague-Dawley rats, aged 10-12 weeks, weighing 200-230 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (Con group), NAFLD group, NAFLD + hepatic I/R group (NAFLD+ HIR group), and NAFLD + hepatic I/R + melatonin treatment group (NAFLD+ HIR+ MT group). The NAFLD model was developed by a high-fat and high-glucose diet (10% glucose, 10% fat) for 8 consecutive weeks in NAFLD, NAFLD+ HIR and NAFLD+ HIR+ M groups, and rats were fed with common chow and freely drank water in the other groups.Melatonin 10 mg/kg was given intragastrically daily for 2 consecutive weeks before developing the model in group NAFLD+ HIR+ MT.The model of liver I/R injury was developed by clipping the hepatic artery and portal vein for 20 min, opening for 5 min, and re-clamping for 20 min followed by restoration of perfusion.Blood samples from inferior vena cava were collected and liver tissues were obtained at 6 h of reperfusion to detect serum levels of insulin, blood glucose, free fatty acid (FFA), triglyceride (TG), alanine aminotransferase (ALT), aspartate amino transferase (AST) and ferritin, and insulin resistance index was calculated.The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), reactive oxygen species (ROS) and Fe 2+ in liver tissues were detected by enzyme-linked immunosorbent assay, the pathological changes of liver tissues were examined with a light microscope after hematoxylin-eosin staining.The expression of nuclear factor E2-related factor 2 (Nrf2), lysophosphatidylcholine acyltransferase 3 (LPCAT3), long-chain fatty acyl-CoA synthase 4 (ACSL4) and glutathione peptide peroxidase 4 (GPX4) was detected by Western blot. Results:Compared with Con group, the levels of serum FFA, TG, ALT, AST and ferritin and insulin resistance index were significantly increased, the levels of ROS and Fe 2+ in liver tissues were increased, the levels of GSH-Px and SOD were decreased, the expression of ACSL4 and LPCAT3 was up-regulated, and the expression of Nrf2 and GPX4 was down-regulated in NAFLD group ( P<0.05). Compared with NAFLD group, the serum levels of FFA, TG, ALT, AST and ferritin and insulin resistance index were significantly increased, the levels of ROS and Fe 2+ were decreased, the levels of GSH-Px and SOD were increased, the expression of ACSL4 and LPCAT3 was up-regulated, and the expression of Nrf2 and GPX4 was down-regulated in NAFLD+ HIR group ( P<0.05). Compared with NAFLD+ HIR group, the serum levels of FFA, TG, ALT, AST and ferritin and insulin resistance index were significantly increased, the levels of ROS and Fe 2+ were decreased, the levels of GSH-Px and SOD were increased, the expression of ACSL4 and LPCAT3 was down-regulated, and the expression of Nrf2 and GPX4 was up-regulated in NAFLD+ HIR+ MT group ( P<0.05). Conclusions:Melatonin preconditioning can alleviate hepatic I/R injury in rats with NAFLD, and the mechanism may be related to activation of Nrf2 signaling pathway, reduction of lipid peroxidation and inhibition of ferroptosis.

6.
Chinese Critical Care Medicine ; (12): 207-210, 2022.
Article in Chinese | WPRIM | ID: wpr-931852

ABSTRACT

The etiology of neonatal lung injury is complicated. Because neonatal lungs are immature in the vesicles and alveolar period, they are easy to be injured by various factors. Clinically, the main manifestations of neonatal lung injury are refractory hypoxemia, respiratory distress, and decreased lung compliance, etc. In recent years, newborn treatment technology has been rapidly developed, but the incidence of neonatal lung injury is still very high, so more attention has been paid by the medical community. Oxidative stress refers to a state of imbalance between oxidation and antioxidant in the body. After newborns transition from amniotic fluid to the air, oxidative stress is relatively higher in the first few weeks of life, and oxidative stress injury will be further aggravated under the stimulation of adverse factors. Melatonin, as an important antioxidant factor in the human body, participates in many vital physiological and pathological processes, and can directly scavenge oxygen free radicals, enhance the activity of antioxidant enzymes, inhibit cell apoptosis. Researches have showed that the antioxidant properties of melatonin played an important role in neonatal lung injury, however, the specific mechanism has not yet been fully clarified. The aim of this article is to review the antioxidant effects of melatonin in neonatal lung injury and provide new ideas for the treatment of neonatal lung injury.

7.
Article in Chinese | WPRIM | ID: wpr-931089

ABSTRACT

Objective:To investigate the inhibitory effect of melatonin on pyroptosis of lens epithelium cells (HLECs) induced by hydrogen peroxide (H 2O 2) and its mechanism. Methods:The cultured HLECs were divided into normal control group, model control group, melatonin group, vitamin E group, and vitamin E solvent group.Cells in melatonin group, vitamin E group and vitamin E solvent group were pre-cultured with 1×10 -6 mol/L melatonin, 100 μmol/L vitamin E or equal volume of vitamin E solvent, then cultured with 100 μmol/L H 2O 2, respectively, and the cells in the normal control group and model control group were cultured with normal condition or 100 μmol/L H 2O 2, respectively.The HLECs transfected with nuclear factor erythroid 2-related factor 2 short hairpin RNA (shNrf2) or shNrf2 negtive control lentivirus and following with 100 μmol/L H 2O 2 treatment were served as shNrf2 group and shNrf2 negative control group, respectively; and the transfected cells treated with 1×10 -6 mol/L melatonin and subsequent 100 μmol/L H 2O 2 treatment were served as melatonin+ shNrf2 group and melatonin+ shNrf2 negative control group.The activity of lactic dehydrogenase (LDH) and the expression levels of interleukin (IL)-1β and IL-18 in the culture supernatant were detected by the enzyme linked immunosorbent assay (ELISA) kit.The concentration of reactive oxygen species (ROS) was assessed by flow cytometry.The expression level of Nrf2, NLRP3, apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), caspase-1 p20 and GSDMD-N proteins were evaluated by Western blot. Results:Compared with model control group, the activity of LDH and the concentrations of IL-1β and IL-18 were significantly decreased in melatonin group and vitamin E group, showing statistically significant differences (all at P<0.05). The ROS fluorescence intensities were 13 040.67±1 550.66 and 12 593.67±1 677.06 in melatonin group and vitamin E group, respectively, which were significantly lower than 18 310.33±1 248.01 in model control group (both at P<0.05). The relative expression levels of Nrf2 protein were 4.24±0.44 and 3.73±0.38 in melatonin group and vitamin E group, respectively, which were significantly higher than 2.28±0.34 in model control group, and the relative expression levels of NLRP3, ASC, caspase-1 p20 and GSDMD-N in melatonin group and vitamin E group were significantly decreased than model control group (all at P<0.05). The relative expression level of Nrf2 protein in shNrf2 group and melatonin+ shNrf2 group was significantly reduced, and the expression levels of LDH, IL-1β, IL-18, ROS content, NLRP3, ASC, caspase-1 p20 and GSDMD-N were significantly increased in comparison with shNrf2 negative control group and melatonin+ shNrf2 negative control group, respectively (all at P<0.05). Conclusions:Melatonin can inhibit the release of NLRP3 inflammasome by activating Nrf2, and has an inhibitory effect on the pyroptosis of HLECs.

8.
Acta cir. bras ; 37(2): e370208, 2022. graf
Article in English | LILACS, VETINDEX | ID: biblio-1374071

ABSTRACT

Purpose: The present study explored the role of melatonin in cisplatin-induced cardiac injury along with the possible role of brain-derived neurotrophic factor (BDNF) in melatonin-mediated effects. Methods: Wistar rats were administered cisplatin (10 mg/kg), and cardiac injury was assessed by measuring the levels of cardiac troponin (cTnT) and lactate dehydrogenase (LDH-1).The extent of apoptosis was measured by measuring caspase-3 (pro-apoptotic) and Bcl-2 (anti-apoptotic) in hearts. The levels of BDNF, tumour necrosis factor α (TNF-α) and reduced glutathione were measured in heart. Melatonin (5 and 10 mg/kg) was administered for 15 days, and the role of BDNF was identified by co-administering BDNF inhibitor, ANA-12 (0.25 and 0.5 mg/kg). Results: Melatonin attenuated cTnT and LDH-1 levels along with reduction in caspase-3 and increase in Bcl-2. It also increased cisplatin-induced decrease in BDNF, increase in TNF-α and decrease in reduced glutathione levels. Moreover, ANA-12 abolished the cardioprotective effects, anti-inflammatory and antioxidant effects of melatonin suggesting the role of BDNF in melatonin-mediated effects in cisplatin-induced cardiac injury. Conclusions: Melatonin is useful in cisplatin-induced cardiac injury, which may be due to an increase in BDNF, decrease in inflammation and increase in antioxidant activities.


Subject(s)
Animals , Rats , Tumor Necrosis Factor-alpha/analysis , Cisplatin/toxicity , Brain-Derived Neurotrophic Factor/analysis , Melatonin/analysis , Cardiotoxicity/drug therapy , Cardiotoxicity/veterinary
9.
Braz. j. med. biol. res ; 55: e11614, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1360238

ABSTRACT

The aim of the present investigation was to study the toxic influences of taxol (TXL) on the testes of rats and the protective impact of melatonin (MLT) against such effects. Rats were classified into control, sham, TXL, MLT, and MLT+TXL-treated groups. Histological and ultrastructural changes were observed in testicular tissues of TXL-intoxicated rats including thickening of tunica albuginea and degenerative alterations in spermatogenic, Sertoli, and Leydig cells. A significant increase (P≤0.05) was found in the thickness of tunica albuginea and numbers of tubules without sperm, apoptotic germinal epithelia, and apoptotic Leydig cells, whereas the diameter of tubules and height of germinal epithelia displayed a significant decrease (P≤0.05) compared with the control, sham, and MLT-treated groups. Immunohistochemically, a marked decrease (P≤0.05) in Bcl-2 immunoreactivity and significant elevation (P≤0.05) in P53 and caspase-3 immunoreactivities were recorded. Co-treatment of MLT and TXL modulated such histological, histomorphometrical, and ultrastructural changes induced by TXL. Also, MLT had a protective effect against testicular apoptosis induced by TXL, as shown by the elevated expression of Bcl-2 and decreased expression of P53 and caspase-3. In conclusion, the current investigation proved that MLT had a protective role against TXL-induced testicular cytotoxicity, which may be a result of inhibition of testicular apoptosis.

10.
Biol. Res ; 552022.
Article in English | LILACS-Express | LILACS | ID: biblio-1403571

ABSTRACT

Abstract Background: Ionizing radiations (IR) have widespread useful applications in our daily life; however, they have unfavorable effects on reproductive health. Maintaining testicular health following IR exposure is an important requirement for reproductive potential. The current study explored the role of melatonin (MLT) in mitigating IR-induced injury in young adult rat testis. Methods: Rats were given daily MLT (25 mg/kg) for 3 and 14 days after receiving 4 Gy γ-radiation. Results: Serum MLT levels and other antioxidants, including glutathione content, and the activity of glutathione peroxidase and glutathione reductase in the testis of the irradiated rats were remarkably maintained by MLT administration in irradiated rats. Hence, the hydrogen peroxide level declined with remarkably reduced formation of oxidative stress markers, 4-hydroxynonenal, and 8-Hydroxy-2′-deoxyguanosine in the testis of irradiated animals after MLT administration. The redox status improvement caused a remarkable regression of proapoptotic protein (p53, Cyto-c, and caspase-3) in the testis and improved inflammatory cytokines (CRP and IL-6), and anti-inflammatory cytokine (interleukin IL-10) in serum. This is associated with restoration of disturbed sex hormonal balance, androgen receptor upregulation, and testicular cell proliferation activity in irradiated rats, explaining the improvement of sperm parameters (count, motility, viability, and deformation). Consequently, spermatogenic cell depletion and decreased seminiferous tubule diameter and perimeter were attenuated by MLT treatment post irradiation. Moreover, the testis of irradiated-MLT-treated rats showed well-organized histological architecture and normal sperm morphology. Conclusions: These results show that radiation-induced testicular injury is mitigated following IR exposure through synergistic interdependence between the antioxidant, anti-inflammatory, anti-apoptotic, and anti-DNA damage actions of MLT.

11.
Clinics ; 77: 100119, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1404319

ABSTRACT

Abstract Objectives: This study sought to further verify the protective mechanism of Melatonin (MT) against ovarian damage through animal model experiments and to lay a theoretical and experimental foundation for exploring new approaches for ovarian damage treatment. Method: The wet weight and ovarian index of rat ovaries were weighted, and the morphology of ovarian tissues and the number of follicles in the pathological sections of collected ovarian tissues were recorded. And the serum sex hormone levels, the key proteins of the autophagy pathway (PI3K, AKT, mTOR, LC3II, LC3I, and Agt5) in rat ovarian tissues, as well as the viability and mortality of ovarian granulosa cells in each group were measured by ELISA, western blotting, CCK8 kit and LDH kit, respectively. Results: The results showed that MT increased ovarian weight and improved the ovarian index in ovarian damage rats. Also, MT could improve autophagy-induced ovarian tissue injury, increase the number of primordial follicles, primary follicles, and sinus follicles, and decrease the number of atretic follicles. Furthermore, MT upregulated serum AMH, INH-B, and E2 levels downregulated serum FSH and LH levels in ovarian damage rats and activated the PI3K/AKT/mTOR signaling pathway. Besides, MT inhibited autophagic apoptosis of ovarian granulosa cells and repressed the expression of key proteins in the autophagic pathway and reduced the expression levels of Agt5 and LC3II/I. Conclusions: MT inhibits granulosa cell autophagy by activating the PI3K/Akt/mTOR signaling pathway, thereby exerting a protective effect against ovarian damage.

12.
Braz. J. Pharm. Sci. (Online) ; 58: e19745, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1383961

ABSTRACT

Abstract Carbon tetrachloride (CCl4) represents an organic chemical that causes reactive oxygen species derived organ disturbances including male infertility. Melatonin (MLT) is a neurohormone with strong antioxidant capacity, involved in numerous physiological processes. In this study we evaluated the capability of MLT, administered in a single dose of 50 mg/kg, to preserve the testicular tissue function after an acute administration of CCl4 to rats. The disturbance in testicular tissue and the effects of MLT after CCl4 exposure were estimated using biochemical parameters that enabled us to determine the tissue (anti)oxidant status and the intensity of arginine/nitric oxide metabolism. Also, the serum levels of testosterone and the histopathological analysis of tissue gave us a better insight into the occurring changes. A significant diminution in tissue antioxidant defences, arginase activity and serum testosterone levels, followed by the increased production of nitric oxide and extensive lipid and protein oxidative damage, was observed in the CCl4-treated group. The application of MLT after the CCl4 caused changes, clearly visible at both biochemical and histological level, which could be interpreted mainly as a consequence of general antioxidant system stimulation and a radical scavenger. On the other hand, the application of MLT exerted a limited action on the nitric oxide signalling pathway.

13.
Braz. j. med. biol. res ; 55: e11938, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1384138

ABSTRACT

The aim of this study was to assess the effect of two types of stressors, regarding the extent of involvement of ouabain (OUA), hippocampal sodium/potassium ATPase (NKA) expression, and the hippocampal corticosterone receptors (CR)/melatonin receptors (MR) expression ratio, on the behavioral and cardiovascular responses and on the hippocampal cornu ammonis zone 3 (CA3) and dentate gyrus (DG). Thirty adult male Wistar albino rats aged 7-8 months were exposed to either chronic immobilization or a disturbed dark/light cycle and treated with either ouabain or vehicle. In the immobilized group, in the absence of hippocampal corticosterone (CORT) changes, rats were non-responsive to stress, despite experiencing increased pulse rate, downregulated hippocampal sodium/potassium pump, and enhanced hippocampal CR/MR expression ratio. Prolonged darkness precipitated a reduced upright attack posture, with elevated CORT against hippocampal MR downregulation. Both immobilization and, to a lesser extent, prolonged darkness stress resulted in histopathological and ultrastructural neurodegenerative changes in the hippocampus. OUA administration did not change the behavioral resilience in restrained rats, despite persistence of the underlying biochemical derangements, added to decreased CORT. On the contrary, with exposure to short photoperiods, OUA reverted the behavior towards a combative reduction of inactivity, with unvaried CR/MR and CORT, while ameliorating hippocampal neuro-regeneration, with co-existing NKA and MR repressions. Therefore, the extent of OUA, hippocampal NKA expression, and CR/MR expression, and subsequent behavioral and cardiac responses and hippocampal histopathology, differ according to the type of stressor, whether immobilization or prolonged darkness.

14.
Article in Chinese | WPRIM | ID: wpr-936313

ABSTRACT

OBJECTIVE@#To investigate the effects of melatonin on the growth and metastasis of MDA-MB-231 breast cancer cells and explore the mechanism.@*METHODS@#MDA-MB-231 cells were treated with 1, 3 or 5 mmol/L melatonin, and the changes in cell proliferation were examined using CCK-8 assay. Colony-forming assay and wound healing assay were used to assess the effects of melatonin treatmnent on colony-forming ability and migration of the cells. Flow cytometry and immunofluoresnce assay were employed to examine apoptosis and positive staining for autophagy-related proteins in the cells treated with 3 mmol/L melatonin. The effects of melatonin treatment alone or in combination with 3-methyladenine (3-MA) on the expressions of the proteins associated with autophagy (LC3, P62 and Beclin1), apoptosis (Bcl2 and Bax) and epithelial-mesenchymal transition (E-cadherin and Snail) were examined with Western blotting.@*RESULTS@#Melatonin treatment significantly inhibited the proliferation of breast cancer cells in a concentration- and time-dependent manner (P < 0.05), suppressed colony-forming ability and migration (P < 0.01), and promoted apoptosis of the cells (P < 0.01). Melatonin treatment alone significantly increased the expressions of Bax (P < 0.05), E-cadherin, LC3-II/LC3-I, and Beclin1 and lowered the expressions of Bcl2 (P < 0.05), Snail, P62 (P < 0.05), and Bcl2/Bax ratio (P < 0.01) in the cells, and caused enhanced positive staining of Beclin1 protein and attenuated staining of P62 protein. Compared with melatonin treatment alone, melatonin treatment combined with 3-MA significantly decreased the expressions of Beclin1 (P < 0.001), LC3-II/LC3-I (P < 0.05), Bax (P < 0.01), and E-cadherin (P < 0.001) and increased the expressions of Bcl2 (P < 0.05), Snail, and Bcl2/Bax ratio (P < 0.01).@*CONCLUSION@#Melatonin can induce autophagy of MDA-MB-231 breast cancer cells to inhibit cell proliferation and metastasis and promote cell apoptosis, and suppressing autophagy can weaken the inhibitory effect of melatonin on the growth and metastasis of breast cancer cells.


Subject(s)
Autophagy , Autophagy-Related Proteins/metabolism , Breast Neoplasms , Cell Line, Tumor , Female , Humans , Melatonin/pharmacology
15.
Arq. neuropsiquiatr ; 79(8): 732-742, Aug. 2021. tab, graf
Article in English | LILACS | ID: biblio-1339229

ABSTRACT

ABSTRACT Background: Insomnia is a sleep disorder characterized by difficulty of falling asleep or maintaining sleep, which affects different age groups. Currently, melatonin is used as a therapeutic treatment in cases of insomnia in children, adults, and elderly people. Objective: To evaluate the effectiveness of melatonin in sleep disorders, its dosage, potential adverse effects, as well as labeling laws and regulations in Brazil. Methods: This integrative review was carried out using the Cochrane Library, Medline (Pubmed), and Science Direct databases. Twenty-five articles and three documents available on the Brazilian Society of Endocrinology and Metabology (SBEM) and National Health Surveillance Agency (ANVISA) websites published between 2015 and 2020 were selected to be evaluated in full. Results: It was found that in most of the selected articles the use of melatonin reduces sleep latency. The effective melatonin doses varied according to each age group, from 0.5 to 3 mg in children, 3 to 5 mg in adolescents, 1 to 5 mg in adults, and 1 to 6 mg in elderly people. Side effects are mild when taking usual doses. In Brazil, no registered drug and current regulation on the use and marketing of melatonin has been identified. Conclusion: The use of melatonin is an alternative therapy that can be used for sleeping disorders. According to the evidences found, it did not demonstrate toxicity or severe side effects, nor dependence even when administered at high doses, suggesting that it is a safe medication to treat patients of different ages suffering from sleeping disorders.


RESUMO Antecedentes: Insônia é um distúrbio do sono caracterizado por dificuldade de iniciar e manter o sono, afetando diferentes faixas etárias. Atualmente, a melatonina é utilizada no tratamento de insônia em crianças, adultos e idosos. Objetivo: Avaliar a eficácia da melatonina nos distúrbios do sono, posologia e potenciais efeitos adversos, bem como a regulamentação vigente no Brasil. Métodos: Trata-se de uma revisão integrativa, os artigos foram identificados nas bases de dados Cochrane Library, Medline (Pubmed) e Science Direct, totalizando 25 artigos, e foram selecionados três materiais disponíveis no site da Sociedade Brasileira de Endocrinologia e Metabologia e Agência Nacional de Vigilância Sanitária, publicados entre 2015 e 2020. Resultados: Verificou-se na maioria dos artigos selecionados que a melatonina reduz a latência do sono. Quanto as dosagens de melatonina identificou-se variação em cada faixa etária, para crianças de 0,5 a 3mg; adolescentes de 3 a 5mg; adultos de 1 a 5mg e idosos 1 mg a 6 mg demostraram serem eficazes. Em doses habituais os efeitos colaterais são leves. No Brasil, não foi identificado medicamento registrado e regulamentação vigente sobre o uso e comercialização de melatonina. Conclusão: A utilização da melatonina é uma alternativa que pode ser utilizada em distúrbios do sono. De acordo com as evidências encontradas, não demonstrou toxicidade ou efeitos colaterais severos, nem dependência mesmo em doses elevadas, sendo, portanto, segura para tratamento de pacientes desde crianças a idosos que sofrem de distúrbios do sono.


Subject(s)
Humans , Child , Adolescent , Adult , Aged , Sleep Wake Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/drug therapy , Melatonin/therapeutic use , Sleep , Brazil
16.
Arch. med ; 21(2): 370-385, 2021-04-25.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1291707

ABSTRACT

Objetivo: determinar cambios y correlaciones de niveles salivales de melatonina, ingesta de alimentos, concentraciones séricas de leptina, insulina, glucosa e índice de resistencia a insulina después de siete noches de trabajo nocturno. Se han registrado mayores riesgos de padecer obesidad y diabetes en los trabajadores por turnos, así como, variaciones en las concentraciones de melatonina. Materiales y métodos: estudio exploratorio de tipo descriptivo comparativo; participaron diez hombres, vigilantes de seguridad quienes laboraban turnos diurnos de 6 a.m. a 3 p.m. y nocturnos de 10 p.m. a 6 a.m. Se determinaron variables antropométricas. Durante el último turno diurno y al finalizar el último turno nocturno se estimó la ingesta de alimentos y para medir los diferentes biomarcadores se tomaron muestras de sangre y saliva a las 7 a.m., y a continuación los sujetos recolectaron muestras de saliva a la 1 p.m., 9 p.m. y 2 a.m. Resultados: después de siete noches de trabajo, los niveles de melatonina a la 1 pm, glucemia y leptina fueron mayores, asimismo, el consumo de calorías totales aumentó a expensas de proteínas y carbohidratos. La correlación negativa entre melatonina e insulinorresistencia no fue estadísticamente significativa. Conclusiones: se confirmaron efectos del turno nocturno sobre los niveles de melatonina al día siguiente de culminada la rotación laboral. Durante el turno nocturno, los trabajadores consumieron más calorías y presentaron mayor glucemia, situaciones que incrementan la susceptibilidad a desarrollar obesidad y diabetes. Asimismo, la leptina sérica aumentó, lo que puede acrecentar el riesgo de padecer síndrome metabólico..(Au)


Objective: to determine changes and correlations of salivary melatonin levels, food intake, serum concentrations of leptin, insulin and glucose and insulin resistance index (IRI) after seven night shifts. Higher risk of obesity and diabetes and modifications in melatonin concentrations have been registered in night shift workers. Materials and Methods: ten male security guards who work day shifts from 6 a.m. to 3 p.m. and night shifts from 10 p.m. to 6 a.m. were chosen to participate in this comparative - descriptive exploratory study. Anthropometric variables from the subjects were taken. Food intake data was taken the last daily shift and after the end of the last night shift. Also blood and saliva samples were taken at 7 a.m. and saliva samples were taken at 1 p.m. 9 p.m and 2 p.m in order to determine several biochemical parameters. Results: after seven nights of work, the levels of melatonin, glycemia and leptin at 1pm were greater. Total consumption of calories increased, at the expense of proteins and carbohydrates. The negative correlation between melatonin and insulin resistance was not statistically significant. Conclusions: the effects of the night shift over melatonin levels were confirmed the day after the work shift ended. Throughout the night shift, workers consumed more calories, and had higher levels of glycemia increasing the risk of developing obesity and diabetes. Leptin level increases were also observed, which may increment the risk of suffering metabolic syndrome..(Au)

17.
Article in Chinese | WPRIM | ID: wpr-880839

ABSTRACT

OBJECTIVE@#To evaluate the effect of general anesthesia on postoperative melatonin secretion in 4-to 6-year-old children with snoring.@*METHODS@#Twenty children with snoring aged 4-6 years of either gender (ASA grade Ⅰ and Ⅱ) were selected for adenoidectomy.Before, during and 3 days after the operation, salivary melatonin levels of the children were measured at 11 selected time points (T1-T11).The illumination intensity and body temperature of the children were recorded at each time point of measurement.The sleep time of the children in 3 days after the operation was recorded, and postoperative pain scores (FLACC) and Riker and Rehabilitation Quality Rating Scale-15(QoR-15) scores were assessed.Sleep Apnea Life Quality Evaluation Questionnaire (OSA-18) was used to evaluate postoperative recovery of the children at 28 days after the operation.The incidence of major adverse events of the children during hospitalization was recorded.@*RESULTS@#No significant difference was found in baseline salivary melatonin level among the 20 children before the operation.Salivary melatonin level at 7 am after the operation (T8) was significantly lowered as compared with that before the surgery (T4)(@*CONCLUSIONS@#In preschool children with snoring, general anesthesia affects but does not inhibit melatonin secretion on the first night after surgery, and minor surgeries under general anesthesia in the morning do not cause significant changes in melatonin secretion to cause disturbance of the circadian rhythm in these children.


Subject(s)
Anesthesia, General/adverse effects , Bodily Secretions , Child , Child, Preschool , Circadian Rhythm , Humans , Melatonin , Snoring
18.
Article in Chinese | WPRIM | ID: wpr-906329

ABSTRACT

Objective:To observe the effects of Cnidii Fructus hypnotic active components (CHC) on the behaviors of rats with p-chlorophenylalanine (PCPA)-induced insomnia and melatonin (MT) synthesis rate-limiting enzyme arylalkylamine <italic>N</italic>-acetyltransferase (AANAT), and explore the protective mechanism of CHC on the pineal gland. Method:Male SD rats of SPF grade were randomly divided into a blank control group, a model group, a MT group, and high-, medium-, and low-dose CHC groups with 10 rats in each group. Except for the blank control group, other groups received 4.5% PCPA suspension at 10 mL·kg<sup>-1</sup>, intragastric administration, for two consecutive days. After PCPA model of insomnia was established, normal and model groups were gavaged at the same volume of 2% Tween-80, MT control group (10 mg·kg<sup>-1</sup>), CHC was high, medium and low (60, 30, 15 mg·kg<sup>-1</sup>), 10 mL·kg<sup>-1</sup>, once a day, for consecutive 7 days. Four days after administration, open field, elevated cross maze, and pentobarbital sodium-induced sleep tests were conducted, respectively. Serum MT was detected by enzyme-linked immunosorbent assay. The mRNA expression level of AANAT was determined by real-time fluorescence-based quantitative polymerase chain reaction (Real-time PCR). The expression of AANAT protein in the pineal gland was detected by Western blot. Result:Compared with the results in the blank control group, the total distance of open field activity and standing times and duration in the central area were increased (<italic>P</italic><0.05, <italic>P</italic><0.01), the proportions of open arm entry (OE%) and open arm time (OT%) were decreased (<italic>P</italic><0.05), and the sleep latency was prolonged (<italic>P</italic><0.01) in the model group. Compared with the model group, no significant difference was observed in the low-dose CHC group, while other groups exhibited reduced total distance of activity (<italic>P</italic><0.05, <italic>P</italic><0.01), elevated OE% (<italic>P</italic><0.05), shortened sleep latency, and prolonged sleep time (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the serum MT in the blank control group, that in the model group was decreased (<italic>P</italic><0.01). Compared with the model group, no significant difference was observed in the low-dose CHC group, while other groups displayed increased serum MT (<italic>P</italic><0.05). The mRNA and protein expression of AANAT was decreased in the model group as compared with that in the blank control group (<italic>P</italic><0.01). Compared with the model group, the MT group and the high-dose CHC group showed up-regulated expression (<italic>P</italic><0.05). Conclusion:CHC improved the behavioral indexes of PCPA-induced insomnia, increased the synthesis and secretion of MT in pineal cells, and elevated the serum MT level, which was related to the up-regulation of the mRNA and protein expression of AANAT in the pineal gland.

19.
Article in Chinese | WPRIM | ID: wpr-906123

ABSTRACT

Objective:To investigate the effect of iron nanoparticles and melatonin on yield and quality of <italic>Fritillaria przewalskii</italic> and provide technical support for its domesticated cultivation. Method:Hundred grain weight was measured by conventional method;alkaloid content was detected according to protocols of the edition of 2020 <italic>Chinese Pharmacopoeia</italic>,chlorophyll,hydrogen peroxide,malondialdehyde,superoxide dismutase (SOD),peroxidase (POD) and catalase (CAT) were detected by spectrophotometric analysis,auxins,cytokinins,gibberellins,salicylic acid,jasmonic acid and abscisic acid were detected by ultra performance liquid chromatography tandem mass spectrometry analysis. Result:Zero-valent iron nanoparticles and melatonin significantly increased the hundred grain weight without affecting the quality. The effect of the two treatments on physiological and biochemical indexes in different stages were quite different,but the effects on content of endogenous hormones were basically the same. Correlation analysis showed that hundred grain weight was negatively correlated with malondialdehyde content,SOD activity and jasmonic acid content,but positively correlated with POD activity,salicylic acid content,gibberellins content,auxin content and abscisic acid content. The two treatments were separated effectively by principal component analysis,indicating that there were some differences in the mechanisms of growth promoting. The treatment of zero-valent iron nanoparticles mainly affected auxins,salicylic acid and abscisic acid. The treatment of melatonin mainly affected SOD,malondialdehyde and gibberellins. Conclusion:Zero-valent iron nanoparticles and melatonin can be used as a simple and practical technology to improve the stress resistance and yields of <italic>F. przewalskii</italic> in domesticated cultivation conditions.

20.
Article in Chinese | WPRIM | ID: wpr-904348

ABSTRACT

Objective To explore the improvement effect of typical hot spring bathing on sleep and anxiety and its correlation with serum melatonin level in Guizhou province. Methods Five typical characteristic hot springs in Guizhou were selected according to the geological type of hot spring water. A total of 226 residents in these areas were selected for the survey and the self-rating scale of sleep(SRSS)and the self-rating anxiety scale(SAS)were used to measure their scores before and after hot spring bathing, and the correlation between the changes of SRSS and SAS scores and the serum melatonin levels were analyzed. Results The SRSS and SAS scores of the respondents after hot spring bathing were lower than before, and the difference was statistically significant(P < 0.05). Serum melatonin levels after hot spring bathing were significantly higher than before(P < 0.05), and there was a negative correlation between the changes of SRSS and SAS scores and serum melatonin levels(P < 0.05). Conclusion Typical hot springs in Guizhou Province can significantly improve the sleep quality and anxiety state, which are related to the elevation of serum melatonin level.

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