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1.
Sci Rep ; 14(1): 15215, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956409

RESUMO

Increasing evidence has shown that many environmental and toxic factors can cause testicular damage, leading to testicular ferroptosis and subsequent male reproductive disorders. Melatonin is a major hormone and plays an vital role in regulating male reproduction. However, there is a lack of research on whether Mel can alleviate testicular cell ferroptosis and its specific mechanism. In this study, the results indicated that Mel could enhance the viability of swine testis cells undergoing ferroptosis, reduce LDH enzyme release, increase mitochondrial membrane potential, and affect the expression of ferroptosis biomarkers. Furthermore, we found that melatonin depended on melatonin receptor 1B to exert these functions. Detection of MMP and ferroptosis biomarker protein expression confirmed that MT2 acted through the downstream Akt signaling pathway. Moreover, inhibition of the Akt signaling pathway can eliminate the protective effect of melatonin on ferroptosis, inhibit AMPK phosphorylation, reduce the expression of mitochondrial gated channel (VDAC2/3), and affect mitochondrial DNA transcription and ATP content. These results suggest that melatonin exerts a beneficial effect on mitochondrial function to mitigate ferroptosis through the MT2/Akt signaling pathway in ST cells.


Assuntos
Ferroptose , Melatonina , Mitocôndrias , Proteínas Proto-Oncogênicas c-akt , Receptor MT2 de Melatonina , Transdução de Sinais , Testículo , Animais , Melatonina/farmacologia , Masculino , Ferroptose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Suínos , Testículo/metabolismo , Testículo/efeitos dos fármacos , Receptor MT2 de Melatonina/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos
2.
PeerJ ; 12: e17608, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978756

RESUMO

According to our preliminary study, melatonin and its N-amide derivatives (N-(2-(1-4-bromobenzoyl-5-methoxy-1H-indol-3-yl)ethyl)acetamide (BBM) and 4-bromo-N-(2-(5-methoxy-1H-indol-3-yl)ethyl)benzamide (EBM)) inhibited the marker of acute inflammation in tests in vitro and in vivo. The anti-inflammatory agent is intended for the prevention and treatment of chemotherapy-induced toxicity. In this study aimed to evaluate the effect of melatonin and its derivatives on mechanisms related to chemotherapy-induced oral mucositis by in vitro ROS and 5-FU-induced human keratinocyte cells as well as in vivo oral mucositis model. In in vitro H2O2-induced HaCaT cells, BBM had the highest level of protection (34.57%) at a concentration 50 µM, followed by EBM (26.41%), and melatonin (7.9%). BBM also protected cells against 5-FU-induced to 37.69-27.25% at 12.5-100 µM while EBM was 36.93-29.33% and melatonin was 22.5-11.39%. In in vivo 5-FU-induced oral mucositis in mice, melatonin, BBM, and EBM gel formulations protected tissue damage from 5-FU similar to the standard compound, benzydamine. Moreover, the weight of mice and food consumption recovered more quickly in the BBM group. These findings suggested that it was possible to develop BBM and EBM as new therapeutic agents for the treatment of oral mucositis.


Assuntos
Melatonina , Estomatite , Melatonina/farmacologia , Melatonina/uso terapêutico , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Estomatite/prevenção & controle , Estomatite/patologia , Animais , Humanos , Camundongos , Queratinócitos/efeitos dos fármacos , Fluoruracila/efeitos adversos , Fluoruracila/toxicidade , Masculino , Espécies Reativas de Oxigênio/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia
3.
Reprod Domest Anim ; 59(7): e14668, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38982684

RESUMO

The aim of this study was to determine the effect of exogenous melatonin administration on transferable embryos by increasing total antioxidant status before superovulation in Assaf ewes. Selected ewes were randomly divided into two equal groups: melatonin (n = 9) and control (n = 9). In the melatonin group, a melatonin implant (18 mg melatonin, Regulin®, Ceva, Turkey) was placed under the skin of the ear 7 days prior to insertion of the progesterone-containing sponge. In the control group, a physiological saline solution was injected under the skin of the ear on the same day. The same superovulation protocol was used in both groups. In addition, blood samples for determination of Glutathione peroxidase, superoxide dismutase, total antioxidant status and total oxidant status concentrations were collected on five different days, including the day of melatonin implant placement (Day-7), vaginal sponge insertion (Day 0), vaginal sponge removal (Day 11), mating (Day 12-13) and uterine flushing (Day 19). Embryos were collected by laparotomy on the 7th day after mating. Uterine flushing taken into petri dishes were scanned under a stereomicroscope, and the quality and developmental stages of the embryos were recorded. In the study, total corpus luteum count and total cell count were found to be higher in the control group than in the melatonin group (p < .05). When the results were evaluated in terms of oxidative stress index, a negative correlation was found between the total number of corpus luteum, number of cells obtained, count of transferable embryos and number of Grade 1 embryos on Day 0. There was also a positive correlation oxidative stress index and the number of unfertilized oocytes on Day-7. As a result, exogenous melatonin administration prior to superovulation during the breeding season is thought to have a negative effect on embryo yield and quality. Therefore, the use of exogenous melatonin in MOET studies during the breeding season is recommended to be investigated in new studies.


Assuntos
Antioxidantes , Transferência Embrionária , Melatonina , Superovulação , Animais , Melatonina/farmacologia , Melatonina/administração & dosagem , Feminino , Superovulação/efeitos dos fármacos , Antioxidantes/farmacologia , Transferência Embrionária/veterinária , Carneiro Doméstico , Gravidez , Corpo Lúteo/efeitos dos fármacos , Ovinos/embriologia
4.
Clinics (Sao Paulo) ; 79: 100397, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38971124

RESUMO

BACKGROUND: Melatonin is a hormone produced by the pineal gland and it has antioxidant properties. AIM: This study aimed to evaluate the effects of melatonin on assisted reproductive technologies through a systematic review and a meta-analysis. MATERIALS AND METHODS: Search strategies were used in PubMed and in other databases covering the last 15 years. After screening for eligibility, 17 articles were selected for the systematic review. For the meta-analysis statistics, two groups were formed, the treatment group (with melatonin) and the control group (without melatonin) for various assisted reproduction outcomes. RESULTS: The main results were that no statistical differences were found concerning the clinical pregnancy outcome (p = 0.64), but there was a statistical difference with respect to Mature Oocytes (MII) (p = 0.001), antral follicle count (p = 0.0002), and the fertilization rate (p ≤ 0.0001). CONCLUSIONS: Melatonin had beneficial effects such as the improvement in the fertilization rate, although the authors did not obtain significance in the clinical pregnancy rate.


Assuntos
Melatonina , Taxa de Gravidez , Melatonina/uso terapêutico , Melatonina/farmacologia , Humanos , Feminino , Gravidez , Técnicas de Reprodução Assistida , Antioxidantes/farmacologia , Fertilização in vitro/métodos , Fertilização in vitro/efeitos dos fármacos , Resultado da Gravidez , Fertilização/efeitos dos fármacos , Fertilização/fisiologia
5.
J Pineal Res ; 76(5): e12989, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38978438

RESUMO

Colistin is renowned as a last-resort antibiotic due to the emergence of multidrug-resistant pathogens. However, its potential toxicity significantly hampers its clinical utilization. Melatonin, chemically known as N-acetyl-5-hydroxytryptamine, is an endogenous hormone produced by the pineal gland and possesses diverse biological functions. However, the protective role of melatonin in alleviating antibiotic-induced intestinal inflammation remains unknown. Herein, we reveal that colistin stimulation markedly elevates intestinal inflammatory levels and compromises the gut barrier. In contrast, pretreatment with melatonin safeguards mice against intestinal inflammation and mucosal damage. Microbial diversity analysis indicates that melatonin supplementation prevents a reduction in the abundance of Erysipelotrichales and Bifidobacteriales, as well as an increase in Desulfovibrionales abundance, following colistin exposure. Remarkably, short-chain fatty acids (SCFAs) analysis shows that propanoic acid contributes to the protective effect of melatonin on colistin-induced intestinal inflammation. Furthermore, the protection effects of melatonin and propanoic acid on LPS-induced cellular inflammation in RAW 264.7 cells are confirmed. Mechanistic investigations suggest that intervention with melatonin and propanoic acid can repress the activation of the TLR4 signal and its downstream NF-κB and MAPK signaling pathways, thereby mitigating the toxic effects of colistin. Our work highlights the unappreciated role of melatonin in preventing the potential detrimental effects of colistin on intestinal health and suggests a combined therapeutic strategy to effectively manage intestinal infectious diseases.


Assuntos
Colistina , Disbiose , Microbioma Gastrointestinal , Melatonina , Melatonina/farmacologia , Animais , Camundongos , Colistina/efeitos adversos , Disbiose/induzido quimicamente , Disbiose/metabolismo , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Células RAW 264.7 , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Masculino , Antibacterianos/farmacologia , Camundongos Endogâmicos C57BL
6.
J Pineal Res ; 76(5): e12987, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38975671

RESUMO

Sleep deprivation (SD) has been associated with a plethora of severe pathophysiological syndromes, including gut damage, which recently has been elucidated as an outcome of the accumulation of reactive oxygen species (ROS). However, the spatiotemporal analysis conducted in this study has intriguingly shown that specific events cause harmful damage to the gut, particularly to goblet cells, before the accumulation of lethal ROS. Transcriptomic and metabolomic analyses have identified significant enrichment of metabolites related to ferroptosis in mice suffering from SD. Further analysis revealed that melatonin could rescue the ferroptotic damage in mice by suppressing lipid peroxidation associated with ALOX15 signaling. ALOX15 knockout protected the mice from the serious damage caused by SD-associated ferroptosis. These findings suggest that melatonin and ferroptosis could be targets to prevent devastating gut damage in animals exposed to SD. To sum up, this study is the first report that proposes a noncanonical modulation in SD-induced gut damage via ferroptosis with a clearly elucidated mechanism and highlights the active role of melatonin as a potential target to maximally sustain the state during SD.


Assuntos
Ferroptose , Melatonina , Camundongos Knockout , Privação do Sono , Animais , Camundongos , Melatonina/metabolismo , Melatonina/farmacologia , Privação do Sono/metabolismo , Masculino , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Peroxidação de Lipídeos , Araquidonato 15-Lipoxigenase/metabolismo , Araquidonato 15-Lipoxigenase/genética , Araquidonato 12-Lipoxigenase
7.
J Pineal Res ; 76(5): e12988, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38982751

RESUMO

Vulnerable atherosclerotic plaque rupture, the leading cause of fatal atherothrombotic events, is associated with an increased risk of mortality worldwide. Peroxisome proliferator-activated receptor delta (PPARδ) has been shown to modulate vascular smooth muscle cell (SMC) phenotypic switching, and, hence, atherosclerotic plaque stability. Melatonin reportedly plays a beneficial role in cardiovascular diseases; however, the mechanisms underlying improvements in atherosclerotic plaque vulnerability remain unknown. In this study, we assessed the role of melatonin in regulating SMC phenotypic switching and its consequential contribution to the amelioration of atherosclerotic plaque vulnerability and explored the mechanisms underlying this process. We analyzed features of atherosclerotic plaque vulnerability and markers of SMC phenotypic transition in high-cholesterol diet (HCD)-fed apolipoprotein E knockout (ApoE-/-) mice and human aortic SMCs (HASMCs). Melatonin reduced atherosclerotic plaque size and necrotic core area while enhancing collagen content, fibrous cap thickness, and smooth muscle alpha-actin positive cell coverage on the plaque cap, which are all known phenotypic characteristics of vulnerable plaques. In atherosclerotic lesions, melatonin significantly decreased the synthetic SMC phenotype and KLF4 expression and increased the expression of PPARδ, but not PPARα and PPARγ, in HCD-fed ApoE-/- mice. These results were subsequently confirmed in the melatonin-treated HASMCs. Further analysis using PPARδ silencing and immunoprecipitation assays revealed that PPARδ plays a role in the melatonin-induced SMC phenotype switching from synthetic to contractile. Collectively, we provided the first evidence that melatonin mediates its protective effect against plaque destabilization by enhancing PPARδ-mediated SMC phenotypic switching, thereby indicating the potential of melatonin in treating atherosclerosis.


Assuntos
Fator 4 Semelhante a Kruppel , Melatonina , Miócitos de Músculo Liso , PPAR delta , Placa Aterosclerótica , Animais , Melatonina/farmacologia , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Camundongos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Fator 4 Semelhante a Kruppel/metabolismo , Humanos , PPAR delta/metabolismo , PPAR delta/genética , Camundongos Knockout , Masculino , Camundongos Knockout para ApoE , Fenótipo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Apolipoproteínas E/deficiência , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Músculo Liso Vascular/efeitos dos fármacos , Camundongos Endogâmicos C57BL
8.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000130

RESUMO

Prenatal stress (PNS), which alters the hypothalamic-pituitary-adrenal axis function in the offspring, predisposes to insulin resistance (IR) in later life and is associated with numerous disorders, including cognitive and memory impairments. At present, our main goal is to assess the effects of chronic piromelatine (Pir) administration, a melatonin analogue, on PNS-provoked IR in the periphery and the hippocampus in male and female offspring. Pregnant Sprague-Dawley rats were exposed to chronic stress (one short-term stressor on a daily basis and one long-term stressor on a nightly basis) from the first gestation week until birth. Vehicle or Pir 20 mg/kg were administered intraperitoneally for 21 days. Plasma glucose, serum insulin levels, and the homeostasis model assessment of insulin resistance (HOMA-IR) were determined as markers of peripheral IR. For the hippocampal IR assessment, insulin receptors (IRs) and glucose transporter 4 (GLUT4) were examined. Prenatally stressed offspring of both sexes indicated enhanced plasma glucose and serum insulin concentrations, increased HOMA-IR, and decreased hippocampal GLUT4 only in male rats. The PNS-induced changes were corrected by chronic treatment with Pir. The present results suggest that the melatoninergic compound Pir exerts beneficial effects on altered glucose/insulin homeostasis in PNS-exposed offspring.


Assuntos
Hipocampo , Resistência à Insulina , Insulina , Efeitos Tardios da Exposição Pré-Natal , Ratos Sprague-Dawley , Animais , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Feminino , Gravidez , Masculino , Ratos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Insulina/metabolismo , Insulina/sangue , Glicemia/metabolismo , Estresse Psicológico/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Receptor de Insulina/metabolismo , Melatonina/farmacologia
9.
Sci Rep ; 14(1): 16067, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992206

RESUMO

Nickel (Ni) and copper (Cu) contamination have become major threats to plant survival worldwide. 24-epibrassinolide (24-EBR) and melatonin (MT) have emerged as valuable treatments to alleviate heavy metal-induced phytotoxicity. However, plants have not fully demonstrated the potential mechanisms by which these two hormones act under Ni and Cu stress. Herein, this study investigated the impact of individual and combined application of 24-EBR and MT on the growth and physiological traits of Primula forbesii Franch. subjected to stress (200 µmol L-1 Ni and Cu). The experiments compared the effects of different mitigation treatments on heavy metal (HM) stress and the scientific basis and practical reference for using these exogenous substances to improve HM resistance of P. forbesii in polluted environments. Nickel and Cu stress significantly hindered leaf photosynthesis and nutrient uptake, reducing plant growth and gas exchange. However, 24-EBR, MT, and 24-EBR + MT treatments alleviated the growth inhibition caused by Ni and Cu stress, improved the growth indexes of P. forbesii, and increased the gas exchange parameters. Exogenous MT effectively alleviated Ni stress, and 24-EBR + MT significantly alleviated the toxic effects of Cu stress. Unlike HM stress, MT and 24-EBR + MT activated the antioxidant enzyme activity (by increasing superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)), significantly reduced reactive oxygen species (ROS) accumulation, and regulated ascorbate and glutathione cycle (AsA-GSH) efficiency. Besides, the treatments enhanced the ability of P. forbesii to accumulate HMs, shielding plants from harm. These findings conclusively illustrate the capability of 24-EBR and MT to significantly bolster the tolerance of P. forbesii to Ni and Cu stress.


Assuntos
Brassinosteroides , Cobre , Melatonina , Níquel , Esteroides Heterocíclicos , Brassinosteroides/farmacologia , Brassinosteroides/metabolismo , Melatonina/farmacologia , Melatonina/metabolismo , Esteroides Heterocíclicos/farmacologia , Níquel/toxicidade , Cobre/toxicidade , Fotossíntese/efeitos dos fármacos , Poluentes do Solo/toxicidade , Estresse Fisiológico/efeitos dos fármacos , Antioxidantes/metabolismo , Antioxidantes/farmacologia
10.
Environ Sci Pollut Res Int ; 31(32): 45370-45382, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38965106

RESUMO

Notwithstanding the fact that melatonin (MT) and titanium nanoparticles (Ti NPs) alone have been widely used recently to modulate cadmium (Cd) stress in plants, there is a gap in the comparative impacts of these materials on lowering Cd toxicity in sage plants. The objective of this study was to determine how foliar application of MT and Ti NPs affected the growth, Cd accumulation, photosynthesis, water content, lipid peroxidation, and essential oil (EO) quality and quantity of sage plants in Cd-contaminated soils. A factorial experiment was conducted using MT at 100 and 200 µM and Ti NPs at 50 and 100 mg L-1 topically, together with Cd toxicity at 10 and 20 mg Cd kg-1 soil. The results showed that Cd toxicity decreased plant growth and enhanced lipid peroxidation. The Cd stress at 20 mg kg-1 soil resulted in increases in Cd root (693%), Cd shoot (429%), electrolyte leakage (EL, 29%), malondialdehyde (MDA, 72%), shoot weight (31%), root weight (27%), chlorophyll (Chl) a + b (26%), relative water content (RWC, 23%), and EO yield (30%). The application of MT and Ti NPs controlled drought stress by reducing MDA and EL, enhancing plant weight, Chl, RWC, and EO production, and minimizing Cd accumulation in plant tissues. The predominant compounds in the EO were α-thujone, 1,8-cineole, ß-thujone, camphor, and α-humulene. MT and Ti NPs caused α-thujone to rise, whereas Cd stress caused it to fall. Based on heat map analysis, MDA was the trait that was most sensitive to treatments. In summary, the research emphasizes the possibility of MT and Ti NPs, particularly MT at 200 µM, to mitigate Cd toxicity in sage plants and enhance their biochemical reactions.


Assuntos
Cádmio , Melatonina , Salvia officinalis , Titânio , Cádmio/toxicidade , Titânio/toxicidade , Melatonina/farmacologia , Poluentes do Solo/toxicidade , Nanopartículas Metálicas/toxicidade , Fotossíntese/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos
11.
Mol Biol Rep ; 51(1): 802, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001949

RESUMO

BACKGROUND: Alzheimer's disease is a neurological disease characterized by the build-up of amyloid beta peptide (Aß) and lipopolysaccharide (LPS), which causes synapse dysfunction, cell death, and neuro-inflammation. A maladaptive unfolded protein response (UPR), excessive autophagy, and pyroptosis aggravate the disease. Melatonin (MEL) and hydroxybutyrate (BHB) have both shown promise in terms of decreasing Aß pathology. The goal of this study was to see how BHB and MEL affected the UPR, autophagy, and pyroptosis pathways in Aß1-42 and LPS-induced SH-SY5Y cells. MATERIALS AND METHODS: Human neuroblastoma SH-SY5Y cells were treated with BHB, MEL, or a combination of the two after being exposed to A ß1-42 and LPS. Cell viability was determined using the MTT test, and gene expression levels of UPR (ATF6, PERK, and CHOP), autophagy (Beclin-1, LC3II, P62, and Atg5), and pyroptosis-related markers (NLRP3, TXNIP, IL-1ß, and NFκB1) were determined using quantitative Real-Time PCR (qRT-PCR). For statistical analysis, one-way ANOVA was employed, followed by Tukey's post hoc test. RESULTS: BHB and MEL significantly increased SH-SY5Y cell viability in the presence of A ß1-42 and LPS. Both compounds inhibited the expression of maladaptive UPR and autophagy-related genes, as well as inflammatory and pyroptotic markers caused by Aß1-42 and LPS-induced SH-SY5Y cells. CONCLUSION: BHB and MEL rescue neurons in A ß1-42 and LPS-induced SH-SY5Y cells by reducing maladaptive UPR, excessive autophagy, and pyroptosis. More research is needed to fully comprehend the processes behind their beneficial effects and to discover their practical applications in the treatment of neurodegenerative disorders.


Assuntos
Ácido 3-Hidroxibutírico , Peptídeos beta-Amiloides , Autofagia , Lipopolissacarídeos , Melatonina , Fragmentos de Peptídeos , Piroptose , Resposta a Proteínas não Dobradas , Humanos , Melatonina/farmacologia , Peptídeos beta-Amiloides/metabolismo , Autofagia/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Linhagem Celular Tumoral , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Ácido 3-Hidroxibutírico/farmacologia , Fragmentos de Peptídeos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/tratamento farmacológico , Neuroblastoma/metabolismo , Neuroblastoma/patologia
12.
J Ovarian Res ; 17(1): 138, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965577

RESUMO

BACKGROUND: To investigate whether melatonin supplementation can enhance cardiometabolic risk factors, reduce oxidative stress, and improve hormonal and pregnancy-related factors in patients with PCOS. METHODS: We conducted a systematic search of PubMed/Medline, Scopus, and the Cochrane Library for articles published in English from inception to March 2023. We included randomized controlled trials (RCTs) on the use of melatonin for patients with polycystic ovary syndrome (PCOS). We performed a meta-analysis using a random-effects model and calculated the standardized mean differences (SMDs) and 95% confidence intervals (CIs). RESULTS: Six studies met the inclusion criteria. The result of meta-analysis indicated that melatonin intake significantly increase TAC levels (SMD: 0.87, 95% CI: 0.46, 1.28, I2 = 00.00%) and has no effect on FBS, insulin, HOMA-IR, TC, TG, HDL, LDL, MDA, hs-CRP, mFG, SHBG, total testosterone, and pregnancy rate in patients with PCOS compare to controls. The included trials did not report any adverse events. CONCLUSION: Melatonin is a potential antioxidant that may prevent damage from oxidative stress in patients with PCOS. However, the clear effect of melatonin supplementation on cardiometabolic risk factors, hormonal outcomes, and pregnancy-related outcomes needs to be evaluated further in large populations and long-term RCTs.


Assuntos
Fatores de Risco Cardiometabólico , Suplementos Nutricionais , Melatonina , Estresse Oxidativo , Síndrome do Ovário Policístico , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Melatonina/farmacologia , Melatonina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/sangue , Feminino , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Hormônios/sangue , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/administração & dosagem
13.
BMC Plant Biol ; 24(1): 671, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39004702

RESUMO

BACKGROUND: Water deficiency stress reduces yield in grain legumes, primarily due to a decrease in the pods number. Melatonin (ML) and 24-epibrassinolide (EBL) are recognized for their hormone-like properties that improve plant tolerance to abiotic stresses. This study aimed to assess the impact of different concentrations of ML (0, 100, and 200 µM) and EBL (0, 3, and 6 µM) on the growth, biochemical, and physiological characteristics of chickpea plants under water-stressed conditions. RESULTS: The study's findings indicated that under water-stressed conditions, a decrease in seed (30%) and pod numbers (31%), 100-seed weight (17%), total chlorophyll content (46%), stomatal conductance (33%), as well as an increase in H2O2 (62%), malondialdehyde content (40%), and electrolyte leakage index (40%), resulted in a 40% reduction in chickpea plants grain yield. Our findings confirmed that under water-stressed conditions, seed oil, seed oil yield, and seed protein yield dropped by 20%, 55%, and 36%, respectively. The concurrent exogenous application of ML and EBL significantly reduces oxidative stress, plasma membrane damage, and reactive oxygen species (ROS) content. This treatment also leads to increased yield and its components, higher pigment content, enhanced oil and protein yield, and improved enzymatic and non-enzymatic antioxidant activities such as catalase, superoxide dismutase, polyphenol oxidase, ascorbate peroxidase, guaiacol peroxidase, flavonoid, and carotenoid. Furthermore, it promotes the accumulation of osmoprotectants such as proline, total soluble protein, and sugars. CONCLUSIONS: Our study found that ML and EBL act synergistically to regulate plant growth, photosynthesis, osmoprotectants accumulation, antioxidant defense systems, and maintain ROS homeostasis, thereby mitigating the adverse effects of water deficit conditions. ML and EBL are key regulatory network components in stressful conditions, with significant potential for future research and practical applications. The regulation metabolic pathways of ML and EBL in water-stressed remains unknown. As a result, future research should aim to elucidate the molecular mechanisms by employing genome editing, RNA sequencing, microarray, transcriptomic, proteomic, and metabolomic analyses to identify the mechanisms involved in plant responses to exogenous ML and EBL under water deficit conditions. Furthermore, the economical applications of synthetic ML and EBL could be an interesting strategy for improving plant tolerance.


Assuntos
Brassinosteroides , Cicer , Desidratação , Melatonina , Esteroides Heterocíclicos , Brassinosteroides/farmacologia , Brassinosteroides/metabolismo , Cicer/efeitos dos fármacos , Cicer/fisiologia , Cicer/genética , Cicer/crescimento & desenvolvimento , Cicer/metabolismo , Melatonina/farmacologia , Esteroides Heterocíclicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sinergismo Farmacológico , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/metabolismo , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Sementes/fisiologia
14.
PLoS One ; 19(6): e0304605, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861499

RESUMO

Canine Alopecia X is a non-inflammatory hair loss disorder of unknown etiology that predominantly affects German Spitz dogs. Treatment modalities include hormone and/or melatonin supplementation and low trauma microneedling. Melatonin influences hair growth and pigmentation in several species and presents a low risk of adverse effects when used in dogs with Alopecia X. Photobiomodulation (PBM) is frequently used in human androgenetic alopecia and alopecia areata; despite this, PBM remains unexplored in canine Alopecia X. To address this knowledge gap, sixty dogs of both sexes will be randomly assigned to three groups: (i) melatonin only group (3 mg/Kg, n = 20); (ii) PBM only group (diode laser, wavelength 660nm, 100mw power, with 3 J/point, 2 sessions/week for 3 months, n = 20); (ii) PBM + melatonin group (n = 20). The objective is to determine the potential of PBM alone or in conjunction with melatonin supplementation in promoting hair regrowth (hair density and diameter) by means of dermatoscopy and planimetry over a period of 90 days.


Assuntos
Alopecia , Terapia com Luz de Baixa Intensidade , Melatonina , Animais , Melatonina/uso terapêutico , Melatonina/farmacologia , Cães , Terapia com Luz de Baixa Intensidade/métodos , Alopecia/tratamento farmacológico , Alopecia/radioterapia , Alopecia/veterinária , Masculino , Feminino , Método Duplo-Cego , Doenças do Cão/radioterapia , Cabelo/crescimento & desenvolvimento , Cabelo/efeitos dos fármacos
15.
BMC Plant Biol ; 24(1): 599, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918732

RESUMO

BACKGROUND: Cowpea wilt is a harmful disease caused by Fusarium oxysporum, leading to substantial losses in cowpea production. Melatonin reportedly regulates plant immunity to pathogens; however the specific regulatory mechanism underlying the protective effect of melatonin pretreated of cowpea against Fusarium oxysporum remains known. Accordingly, the study sought to evaluate changes in the physiological and biochemical indices of cowpea following melatonin treated to facilitate Fusarium oxysporum resistance and elucidate the associated molecular mechanism using a weighted gene coexpression network. RESULTS: Treatment with 100 µM melatonin was effective in increasing cowpea resistance to Fusarium oxysporum. Glutathione peroxidase (GSH-PX), catalase (CAT), and salicylic acid (SA) levels were significantly upregulated, and hydrogen peroxide (H2O2) levels were significantly downregulated in melatonin treated samples in roots. Weighted gene coexpression network analysis of melatonin- and Fusarium oxysporum-treated samples identified six expression modules comprising 2266 genes; the number of genes per module ranged from 9 to 895. In particular, 17 redox genes and 32 transcription factors within the blue module formed a complex interconnected expression network. KEGG analysis revealed that the associated pathways were enriched in secondary metabolism, peroxisomes, phenylalanine metabolism, flavonoids, and flavonol biosynthesis. More specifically, genes involved in lignin synthesis, catalase, superoxide dismutase, and peroxidase were upregulated. Additionally, exogenous melatonin induced activation of transcription factors, such as WRKY and MYB. CONCLUSIONS: The study elucidated changes in the expression of genes associated with the response of cowpea to Fusarium oxysporum under melatonin treated. Specifically, multiple defence mechanisms were initiated to improve cowpea resistance to Fusarium oxysporum.


Assuntos
Resistência à Doença , Fusarium , Redes Reguladoras de Genes , Melatonina , Doenças das Plantas , Vigna , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Melatonina/farmacologia , Melatonina/metabolismo , Resistência à Doença/genética , Resistência à Doença/efeitos dos fármacos , Fusarium/fisiologia , Vigna/genética , Vigna/microbiologia , Vigna/efeitos dos fármacos , Vigna/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ácido Salicílico/metabolismo
16.
Int J Mol Sci ; 25(12)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38928338

RESUMO

The flavonoids in citrus fruits are crucial physiological regulators and natural bioactive products of high pharmaceutical value. Melatonin is a pleiotropic hormone that can regulate plant morphogenesis and stress resistance and alter the accumulation of flavonoids in these processes. However, the direct effect of melatonin on citrus flavonoids remains unclear. In this study, nontargeted metabolomics and transcriptomics were utilized to reveal how exogenous melatonin affects flavonoid biosynthesis in "Bingtangcheng" citrus fruits. The melatonin treatment at 0.1 mmol L-1 significantly increased the contents of seven polymethoxylated flavones (PMFs) and up-regulated a series of flavonoid pathway genes, including 4CL (4-coumaroyl CoA ligase), FNS (flavone synthase), and FHs (flavonoid hydroxylases). Meanwhile, CHS (chalcone synthase) was down-regulated, causing a decrease in the content of most flavonoid glycosides. Pearson correlation analysis obtained 21 transcription factors co-expressed with differentially accumulated flavonoids, among which the AP2/EREBP members were the most numerous. Additionally, circadian rhythm and photosynthesis pathways were enriched in the DEG (differentially expressed gene) analysis, suggesting that melatonin might also mediate changes in the flavonoid biosynthesis pathway by affecting the fruit's circadian rhythm. These results provide valuable information for further exploration of the molecular mechanisms through which melatonin regulates citrus fruit metabolism.


Assuntos
Citrus , Flavonoides , Frutas , Regulação da Expressão Gênica de Plantas , Melatonina , Metabolômica , Citrus/metabolismo , Citrus/efeitos dos fármacos , Citrus/genética , Melatonina/farmacologia , Melatonina/metabolismo , Flavonoides/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Frutas/metabolismo , Frutas/efeitos dos fármacos , Frutas/genética , Metabolômica/métodos , Perfilação da Expressão Gênica , Transcriptoma , Metaboloma/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética
17.
Plant Physiol Biochem ; 212: 108779, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823090

RESUMO

Melatonin (Mel) is a phytohormone that plays a crucial role in various plant processes, including stress response. Despite numerous studies on the role of Mel in stress resistance, its significance in plants exposed to benzalkonium chloride (BAC) pollution remains unexplored. BAC, a common antiseptic, poses a threat to terrestrial plants due to its widespread use and inefficient removal, leading to elevated concentrations in the environment. This study investigated the impact of BAC (0.5 mg L-1) pollution on wild-type Col-0 and snat2 knockout mutant Arabidopsis lines, revealing reduced growth, altered water relations, and gas exchange parameters. On the other hand, exogenous Mel (100 µM) treatments mitigated BAC-induced phytotoxicity and increased the growth rate by 1.8-fold in Col-0 and 2-fold in snat2 plants. snat2 mutant seedlings had a suppressed carbon assimilation rate (A) under normal conditions, but BAC contamination led to further A repression by 71% and 48% in Col-0 and snat2 leaves, respectively. However, Mel treatment on stressed plants was successful in improving Fv/Fm and increased the total photosynthesis efficiency by regulating photochemical reactions. Excessive H2O2 accumulation in the guard cells of plants exposed to BAC pollution was detected by confocal microscopy. Mel treatments triggered almost all antioxidant enzyme activities (except POX) in both Arabidopsis lines under stress. This enhanced antioxidant activity, facilitated by foliar Mel application, contributed to the alleviation of oxidative damage, regulation of photosynthesis reactions, and promotion of plant growth in Arabidopsis. In addition to corroborating results observed in many agricultural plants regarding the development of tolerance to environmental stresses, this study provides novel insights into the action mechanisms of Mel under the emerging pollutant benzalkonium chloride.


Assuntos
Antioxidantes , Arabidopsis , Compostos de Benzalcônio , Melatonina , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Melatonina/farmacologia , Compostos de Benzalcônio/farmacologia , Antioxidantes/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Peróxido de Hidrogênio/metabolismo , Fotossíntese/efeitos dos fármacos , Mutação
18.
Int J Mol Sci ; 25(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891855

RESUMO

Melatonin influences arterial biomechanics, and its absence could cause remodeling of the arterial wall, leading to increased stiffness. Direct effects of fentanyl on the aortic wall have also been observed previously. This study aimed to evaluate in vitro the effects of fentanyl on aortic viscoelasticity in a rat model of melatonin deficiency and to test the hypothesis that melatonin deficiency leads to increased arterial wall stiffness. The viscoelasticity was estimated in strip preparations from pinealectomized (pin, melatonin deficiency) and sham-operated (sham, normal melatonin) adult rats using the forced oscillations method. In the untreated aortic wall pin, the viscoelasticity was not significantly altered. However, combined with 10-9 M fentanyl, the pin increased the natural frequency (f0) and modulus of elasticity (E') compared to the sham-operated. Independently, fentanyl treatment decreased f0 and E' compared separately to untreated sham and pin preparations. The effects of fentanyl were neither dose-dependent nor affected by naloxone, suggesting a non-opioid mechanism. Furthermore, an independent effect of naloxone was also detected in the normal rat aortic wall, resulting in reduced E'. Additional studies are needed that may improve the clinical decisions for pain management and anesthesia for certain patients with co-occurring chronic low levels of blood plasma melatonin and some diseases.


Assuntos
Aorta , Elasticidade , Fentanila , Melatonina , Animais , Fentanila/farmacologia , Melatonina/farmacologia , Ratos , Masculino , Aorta/efeitos dos fármacos , Aorta/metabolismo , Elasticidade/efeitos dos fármacos , Viscosidade , Modelos Animais de Doenças , Rigidez Vascular/efeitos dos fármacos , Analgésicos Opioides/farmacologia , Naloxona/farmacologia
19.
Int J Mol Sci ; 25(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38892154

RESUMO

A plethora of pathophysiological events have been shown to play a synergistic role in neurodegeneration, revealing multiple potential targets for the pharmacological modulation of Alzheimer's disease (AD). In continuation to our previous work on new indole- and/or donepezil-based hybrids as neuroprotective agents, the present study reports on the beneficial effects of lead compounds of the series on key pathognomonic features of AD in both cellular and in vivo models. An enzyme-linked immunosorbent assay (ELISA) was used to evaluate the anti-fibrillogenic properties of 15 selected derivatives and identify quantitative changes in the formation of neurotoxic ß-amyloid (Aß42) species in human neuronal cells in response to treatment. Among the most promising compounds were 3a and 3c, which have recently shown excellent antioxidant and anticholinesterase activities, and, therefore, have been subjected to further in vivo investigation in mice. An acute toxicity study was performed after intraperitoneal (i.p.) administration of both compounds, and 1/10 of the LD50 (35 mg/kg) was selected for subacute treatment (14 days) with scopolamine in mice. Donepezil (DNPZ) and/or galantamine (GAL) were used as reference drugs, aiming to establish any pharmacological superiority of the multifaceted approach in battling hallmark features of neurodegeneration. Our promising results give first insights into emerging disease-modifying strategies to combine multiple synergistic activities in a single molecule.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Donepezila , Melatonina , Fármacos Neuroprotetores , Donepezila/farmacologia , Donepezila/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Humanos , Camundongos , Melatonina/farmacologia , Peptídeos beta-Amiloides/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Masculino , Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Indanos/farmacologia , Indanos/uso terapêutico , Modelos Animais de Doenças , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Piperidinas/farmacologia , Piperidinas/uso terapêutico
20.
Nutrients ; 16(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38892585

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder identified by impairments in common social interactions and repetitive behaviors. In ASD patients, substantial morphological alterations have been observed in the hippocampus, which represents an important region for the development of social skills. Melatonin, commonly found in many foods and plants, is also produced by the pineal gland. This indolamine, known to regulate the circadian rhythm, shows antioxidant and anti-inflammatory properties. We therefore hypothesized that melatonin may reduce oxidative stress and inflammation in the hippocampus of ASD patients. We explored our hypothesis using the BTBR mouse, a well-regarded murine transgenic model for ASD. Immediately after weaning, male BTBR and C57BL/6 mice underwent an 8-week treatment with melatonin or vehicle. Later, through immunohistochemistry and the immunoblotting analysis of the hippocampus, we evaluated the overall expression and cellular localization of Nrf2 and SOD1, two enzymes involved in the oxidative stress response. Similarly, we evaluated NLRP3 and NFkB, two mediators of inflammation, and GAD67, an enzyme responsible for the synthesis of GABA. Ultimately, we addressed melatonin's potential to regulate iron metabolism through a DAB-enhanced Perls reaction assay. Results showed melatonin's potential for modulating the analyzed markers in BTBR mice, suggesting a potential neuroprotective effect in ASD patients.


Assuntos
Transtorno do Espectro Autista , Modelos Animais de Doenças , Hipocampo , Melatonina , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores , Estresse Oxidativo , Animais , Melatonina/farmacologia , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/farmacologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/metabolismo , Antioxidantes/farmacologia , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2/metabolismo , Inflamação/metabolismo , Inflamação/prevenção & controle
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