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1.
Theriogenology ; 177: 1-10, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34653791

RESUMO

Chloroquine (CQ) could function as a lysosomotropic agent to inhibit the endolysosomal trafficking in the autophagy pathway, and is widely used on malarial, tumor and recently COVID-19. However, the effect of CQ treatment on porcine immature Sertoli cells (iSCs) remains unclear. Here we showed that CQ could reduce iSC viability in a dose-dependent manner. CQ treatment (20 µM) on iSCs for 36h could elevate oxidative stress, damage mitochondrial function and promote apoptosis, which could be partially rescued by melatonin (MT) (10 nM). Transcriptome profiling identified 1611 differentially expressed genes (DEGs) (776 up- and 835 down-regulated) (20 µM CQ vs. DMSO), mainly involved in MAPK cascade, cell proliferation/apoptosis, HIF-1, PI3K-Akt and lysosome signaling pathways. In contrast, only 467 (224 up- and 243 down-regulated) DEGs (CQ + MT vs. DMSO) could be found after MT (10 nM) addition, enriched in cell cycle, regulation of apoptotic process, lysosome and reproduction pathways. Therefore, the partial rescue effects of MT on CQ treatment were confirmed by multiple assays (cell viability, ROS level, mitochondrial function, apoptosis, and mRNA levels of selected genes). Collectively, CQ treatment could impair porcine iSC viability by deranging the signaling pathways related to apoptosis and autophagy, which could be partially rescued by MT supplementation.


Assuntos
COVID-19 , Melatonina , Doenças dos Suínos , Animais , Apoptose , Autofagia , COVID-19/tratamento farmacológico , COVID-19/veterinária , Cloroquina/farmacologia , Masculino , Melatonina/farmacologia , Fosfatidilinositol 3-Quinases , SARS-CoV-2 , Células de Sertoli , Suínos
2.
Int J Mol Sci ; 22(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34639101

RESUMO

A well-functional intestinal mucosal barrier can be compromised as a result of various diseases, chemotherapy, radiation, and chemical exposures including surfactants. Currently, there are no approved drugs targeting a dysfunctional intestinal barrier, which emphasizes a significant medical need. One candidate drug reported to regulate intestinal mucosal permeability is melatonin. However, it is still unclear if its effect is primarily receptor mediated or antioxidative, and if it is associated with enteric neural pathways. The aim of this rat intestinal perfusion study was to investigate the mechanisms of melatonin and nicotinic acetylcholine receptors on the increase in intestinal mucosal clearance of 51Cr-labeled ethylenediaminetetraacetate induced by 15 min luminal exposure to the anionic surfactant, sodium dodecyl sulfate. Our results show that melatonin abolished the surfactant-induced increase in intestinal permeability and that this effect was inhibited by luzindole, a melatonin receptor antagonist. In addition, mecamylamine, an antagonist of nicotinic acetylcholine receptors, reduced the surfactant-induced increase in mucosal permeability, using a signaling pathway not influenced by melatonin receptor activation. In conclusion, our results support melatonin as a potentially potent candidate for the oral treatment of a compromised intestinal mucosal barrier, and that its protective effect is primarily receptor-mediated.


Assuntos
Permeabilidade da Membrana Celular , Mucosa Intestinal/efeitos dos fármacos , Doenças do Jejuno/prevenção & controle , Jejuno/efeitos dos fármacos , Melatonina/farmacologia , Receptores de Melatonina/metabolismo , Tensoativos/toxicidade , Animais , Antioxidantes/farmacologia , Motilidade Gastrointestinal , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Doenças do Jejuno/induzido quimicamente , Doenças do Jejuno/metabolismo , Doenças do Jejuno/patologia , Jejuno/metabolismo , Jejuno/patologia , Masculino , Ratos , Ratos Wistar , Receptores de Melatonina/genética , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo
3.
J Contemp Dent Pract ; 22(7): 739-744, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34615777

RESUMO

AIM AND OBJECTIVE: To histologically compare alveolar bone repair after tooth extraction treated with melatonin and calcium sulfate in an in vivo experimental study in guinea pigs (Cavia porcellus). MATERIALS AND METHODS: The study was of longitudinal, prospective, and experimental design in an animal bio-model. A total of 24 male guinea pigs were included, weighing from 700 to 900 g and separated into two experimental groups (melatonin and calcium sulfate) for three periods (15, 30, and 45 days) at 15-day intervals after surgery. The guinea pigs were randomly included into groups for the time evaluated. RESULTS: In relation to bone repair cells using calcium sulfate, the presence of osteoblasts at 15, 30, and 45 days was 39.0 ± 63, 55.3 ± 6.0, respectively, with 61.3 ± 10.0 cells per field. Regarding bone repair cells using melatonin, the presence of osteoblasts at 15, 30, and 45 days was 25.0 ± 3.7, 49.3 ± 1.5, respectively, with 53.6 ± 5.6 cells per field. CONCLUSION: Both melatonin and calcium sulfate were found to be useful in bone repair at a histological and clinical level, although they present certain nonsignificant, albeit marked advantages in the bone repair process when compared with the control socket at the histological level. CLINICAL SIGNIFICANCE: This research allows us to know the usefulness of these easily accessible chemicals for the generation of bone repair.


Assuntos
Sulfato de Cálcio , Melatonina , Animais , Cobaias , Masculino , Melatonina/farmacologia , Estudos Prospectivos , Projetos de Pesquisa
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(9): 1409-1414, 2021 Aug 31.
Artigo em Chinês | MEDLINE | ID: mdl-34658357

RESUMO

OBJECTIVE: To explore the effect of melatonin (MT) on 2, 2', 4, 4'-tetrabromodiphenylether (PBDE-47)-induced abnormal autophagy and apoptosis in rat adrenal medullary pheochromocytoma PC12 cells. METHODS: PC12 cells were pretreated with a concentration gradient (12.5, 25, 50, 100, and 200 µmol/L) of melatonin for 2 h before exposure to 20 µmol/L PBDE-47 for 24 h to determine the optimal concentration of melatonin for cell treatment. In subsequent experiments, PC12 cells were treated with 0.5‰ DMSO (control group), 20 µmol/L PBDE-47, 25 µmol/L melatonin, or both PBDE-47 and melatonin. Immunofluorescence assay was used to detect the positive staining of microtubule associated protein 1 light chain 3 (LC3; a marker protein of autophagy); Western blotting was performed to determine the expression levels of the key autophagic proteins including autophagy-related protein 7 (ATG7), LC3-Ⅱ and autophagy substrate p62, and the key apoptotic proteins including active cysteine-containing aspartate specific protease-3 (active caspase-3) and cleaved poly(ADP ribose) polymerase (cleaved PARP). RESULTS: PBDE-47 treatment significantly reduced the viability of PC12 cells (P=0.001), but pretreatment with 25 µmol/L melatonin maintained a cell viability over 80% following exposure to PBDE-47 (P=0.023). PBDE-47-treated PC12 cells showed obviously enhanced immunofluorescent staining of LC3 protein, a significantly decreased expression of ATG7 and increased expression levels of p62, LC3-Ⅱ, active caspase-3 and cleaved PARP (P < 0.001). The cells treated with both PBDE-47 and melatonin showed obviously reduced staining of LC3 protein with a signficantly increased expression level of ATG7 (P=0.034) and decreased expressions of p62 (P=0.048), LC3-Ⅱ (P=0.018), active caspase-3 (P < 0.001) and cleaved PARP (P=0.032). CONCLUSION: PBDE-47 exposure impairs autophagy to cause autophagosome accumulation and promote apoptosis of PC12 cells. Melatonin can improve PBDE-47-induced abnormal autophagy and apoptosis and thus promote the survival of PC12 cells.


Assuntos
Melatonina , Animais , Apoptose , Autofagia , Éteres Difenil Halogenados , Melatonina/farmacologia , Células PC12 , Ratos
5.
Nutrients ; 13(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34684578

RESUMO

In a previous study, we demonstrated that melatonin prevents kidney damage in a salt-induced hypertension model by decreasing oxidative stress. We hypothesized that this effect involves melatonin's immunomodulatory properties. In vivo Study-Dahl salt-sensitive (DSS) rats were fed normal chow, a high-salt diet (HSD), or a HSD and melatonin (30 mg/kg/day) in their water for eight weeks. Kidneys were harvested for immediate lymphocyte isolation and characterization by Flow cytometry (CD3+CD4+ and CD3+CD8+) and for lymphocyte chemoattractant (mainly CXCL chemokines) gene expression studies. In vitro study-rat mesangial cells (RMC) were cultured in a high-salt medium without and with melatonin. A HSD was associated with significant renal infiltration of CD4+ and CD8+ T lymphocytes compared to control. Melatonin significantly reduced renal lymphocyte infiltration. A HSD significantly increased mRNA expression of CXCL chemokines. Adding melatonin to the HSD abolished this effect. Treating RMC cells with salt increased the expression of CXCL10 and CXCL11 but not CXCL9. Adding melatonin to the culture media prevented this increase. Treating HSD-fed rats with melatonin decreased renal lymphocyte chemoattractant mRNA expression and is associated with significantly reducing renal T lymphocyte infiltration. Salt may have a direct effect on chemokine-producing renal cells, which is blunted by melatonin treatment.


Assuntos
Quimiocinas/metabolismo , Hipertensão/imunologia , Rim/imunologia , Melatonina/farmacologia , Receptores CXCR3/metabolismo , Linfócitos T/imunologia , Animais , Linhagem Celular , Hipertensão/prevenção & controle , Rim/efeitos dos fármacos , Ligantes , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Ratos , Ratos Endogâmicos Dahl , Cloreto de Sódio na Dieta , Linfócitos T/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
6.
Ecotoxicol Environ Saf ; 226: 112816, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34597844

RESUMO

Cold stress is an adverse environmental condition that limits the growth and yield of leguminous plants. Thus, discovering an effective way of ameliorating cold-mediated damage is important for sustainable legume production. In this study, the combined use of Rhizobium inoculation (RI) and melatonin (MT) pretreatment was investigated in Medicago truncatula plants under cold stress. Eight-week-old seedlings were divided into eight groups: (i) CK (no stress, noninoculated, no MT), (ii) RI (Rhizobium inoculated), (iii) MT (75 µM melatonin), (iv) RI+MT, (v) CS (cold stress at 4 °C without Rhizobium inoculation and melatonin), (vi) CS+RI, (vii) CS+MT, and (viii) CS+RI+MT. Plants were exposed to cold stress for 24 hrs. Cold stress decreased photosynthetic pigments and increased oxidative stress. Pretreatment with RI and MT alone or combined significantly improved root activity and plant biomass production under cold stress. Interestingly, chlorophyll contents increased by 242.81% and MDA levels dramatically decreased by 34.22% in the CS+RI+MT treatment compared to the CS treatment. Moreover, RI+MT pretreatment improved the antioxidative ability by increasing the activities of peroxidase (POD; 8.45%), superoxide dismutase (SOD; 50.36%), catalase (CAT; 140.26%), and ascorbate peroxidase (APX; 42.63%) over CS treated plants. Additionally, increased osmolyte accumulation, nutrient uptake, and nitrate reductase activity due to the combined use of RI and MT helped the plants counteract cold-mediated damage by strengthening the nonenzymatic antioxidant system. These data indicate that pretreatment with a combined application of RI and MT can attenuate cold damage by enhancing the antioxidation ability of legumes.


Assuntos
Medicago truncatula , Melatonina , Rhizobium , Antioxidantes , Resposta ao Choque Frio , Melatonina/farmacologia , Estresse Oxidativo , Plântula
7.
Ecotoxicol Environ Saf ; 226: 112878, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34634736

RESUMO

Herein, we further document the protective action of melatonin (MLT) in mitigating cadmium (Cd) effects on adult rat testis. Cd treatment provoked testicular injury, that was documented by histological and biomolecular alterations, i.e., decrease of serum and testicular testosterone concentration and modified sperm parameters. Mainly, both the cytoarchitecture of the blood-testis barrier (BTB) and germ cell morphology were perturbed, as highlighted by impairment in structural (OCN, VANGL, Cx43) and regulative (Src and FAK) protein levels and/or activation. The study focused on the involvement of the autophagy pathway, that was enhanced especially in the Sertoli cells, probably in response to the disorganization of the BTB. Results obtained with the MLT co-treatment demonstrated that its administration decreased the level of oxidative damage caused by Cd, with reversal of all the observed changes. Moreover, the beneficial effects of MLT alone were evidenced by an increase of sperm quality, in term of motility and DNA integrity. The combined results, obtained in rat, strongly encourage to consider a role for MLT in improving also human testicular health, not only in men exposed to Cd, but also in those having fertility disorders, to ameliorate sperm quality and, consequently, reproductive success.


Assuntos
Barreira Hematotesticular , Melatonina , Animais , Cádmio/toxicidade , Masculino , Melatonina/farmacologia , Ratos , Espermatozoides , Testículo
8.
Molecules ; 26(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34641628

RESUMO

This work aims to assess the recently established anti-inflammatory and antioxidant potential of melatonin of plant origin extracted from the plant matrix as a phytomelatonin complex (PHT-MLT), and compare its activity with synthetic melatonin (SNT-MLT) when used on its own or with vitamin C. For this purpose, a COX-2 enzyme inhibitory activity test, an antiradical activity in vitro and on cell lines assays, was performed on both PHT-MLT and SNT-MLT products. COX-2 inhibitory activity of PHT-MLT was found to be ca. 6.5 times stronger than that of SNT-MLT (43.3% and 6.7% enzyme inhibition, equivalent to the activity of acetylsalicylic acid in conc. 30.3 ± 0.2 and 12.0 ± 0.3 mg/mL, respectively). Higher antiradical potential and COX-2 inhibitory properties of PHT-MLT could be explained by the presence of additional naturally occurring constituents in alfalfa, chlorella, and rice, which were clearly visible on the HPLC-ESI-QTOF-MS fingerprint. The antiradical properties of PHT-MLT determined in the DPPH test (IC50 of 21.6 ± 1 mg of powder/mL) were found to originate from the presence of other metabolites in the 50% EtOH extract while SNT-MLT was found to be inactive under the applied testing conditions. However, the antioxidant studies on HaCaT keratinocytes stimulated with H2O2 revealed a noticeable activity in all samples. The presence of PHT-MLT (12.5, 25 and 50 µg/mL) and vitamin C (12.5, 25 and 50 µg/mL) in the H2O2-pretreated HaCaT keratinocytes protected the cells from generating reactive oxygen species. This observation confirms that MLT-containing samples affect the intracellular production of enzymes and neutralize the free radicals. Presented results indicated that MLT-containing products in combination with Vitamin C dosage are worth to be considered as a preventive alternative in the therapy of various diseases in the etiopathogenesis, of which radical and inflammatory mechanisms play an important role.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Ciclo-Oxigenase 2/metabolismo , Queratinócitos/citologia , Melatonina/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Antioxidantes/síntese química , Antioxidantes/química , Ácido Ascórbico/farmacologia , Linhagem Celular , Regulação para Baixo , Sinergismo Farmacológico , Radicais Livres/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/efeitos adversos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Melatonina/síntese química , Melatonina/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia
9.
Physiol Plant ; 173(4): 1682-1694, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34716914

RESUMO

Melatonin (MEL) is a ubiquitous molecule with pleiotropic roles in plant adaption to stress. In this study, we investigated the effects of foliar spray of 100 and 200 µM MEL on the biochemical and physiological traits linked with the growth performance of olive seedlings exposed to moderate (45 mM NaCl) and severe (90 mM NaCl) salinity. Both salt stress conditions caused a considerable reduction in leaf relative water content and the contents of photosynthetic pigments (carotenoids, chlorophylls a and b, and total chlorophylls), K+ and Ca+2 , while the contents of Na+ and the activities of antioxidant enzymes increased. In addition, salt-stressed olive seedlings showed high accumulations of hydrogen peroxide (H2 O2 ), malondialdehyde (MDA), and electrolyte leakage (EL), indicating that olive seedlings suffered from salinity-induced oxidative damage. In contrast, MEL application revived the growth of olive seedlings, including shoot height, root length and biomass under salt stress conditions. MEL protected the photosynthetic pigments and decreased the Na+ /K+ ratio under both moderate and severe salt stresses. Furthermore, MEL induced the accumulations of proline, total soluble sugars, glycine betaine, abscisic acid, and indole acetic acid in salt-stressed olive seedlings, which showed a positive correlation with improved leaf water status and biomass. MEL application also increased the activities of catalase, superoxide dismutase, ascorbate peroxidase, and peroxidase in salt-stressed seedlings, resulting in lower levels of H2 O2 , MDA, and EL in these plants. Taken together, MEL mitigates salinity through its roles in various biochemical and physiological processes, thereby representing a promising agent for application in crop protection.


Assuntos
Melatonina , Olea , Antioxidantes , Homeostase , Melatonina/farmacologia , Reguladores de Crescimento de Plantas , Salinidade , Plântula
10.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502152

RESUMO

Major depressive disorder is a disabling disease with the number of affected individuals increasing each year. Current antidepressant treatments take between three to six weeks to be effective with forty percent of patients being resistant to treatment, making it necessary to search for new antidepressant treatments. Ketamine, a phencyclidine hydrochloride derivative, given intravenously, induces a rapid antidepressant effect in humans. In mice, it causes increased neurogenesis and antidepressant-like effects. However, it also produces psychomimetic effects in humans and in rodents increases the locomotor activity. In contrast, melatonin, a hormone secreted by the pineal gland and synthesized in extrapineal sites, increases new neuron formation and causes antidepressant-like effects in adult rodents with no collateral effects. Here, we assessed the effects of a non-effective dose of ketamine in combination with melatonin (KET/MEL), both on neurogenesis as well as on the antidepressant-like effect in mice. Our results showed that KET/MEL combination increased neurogenesis and produced antidepressant-like effects without altering locomotor activity after both single and triple administration protocols. Our data strongly suggest that KET/MEL combination could be used to simultaneously promote neurogenesis, reverting neuronal atrophy and inducing antidepressant-like effects.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Ketamina/uso terapêutico , Melatonina/uso terapêutico , Animais , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Combinação de Medicamentos , Sinergismo Farmacológico , Ketamina/administração & dosagem , Ketamina/farmacologia , Masculino , Melatonina/administração & dosagem , Melatonina/farmacologia , Camundongos , Neurogênese/efeitos dos fármacos
11.
Plant Physiol Biochem ; 167: 958-969, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34571389

RESUMO

Melatonin is a pleiotropic regulatory molecule in plants and is involved in regulating plant tolerance to drought stress. Here, we conducted transcriptomic and physiological analyses to identify metabolic processes associated with the enhanced tolerance of the melatonin-treated maize (Zea mays L.) seedlings to water deficit. Maize seedlings were foliar sprayed with either 50 µM melatonin or water and exposed to drought stress for 12 d in growth chambers. Drought stress significantly suppressed seedling growth, and melatonin application partially alleviated this growth inhibition. RNA-Seq analysis revealed that genes whose expression was significantly altered by melatonin were mainly related to carbon (C) and nitrogen (N) metabolism. Analysis of transcriptomics, enzyme activity, and metabolite content data, melatonin-treated plants exhibited a higher level of relatively stable C and N metabolism than untreated plants; this phenotype of melatonin-treated plants was associated with their higher photosynthesis, sucrose biosynthesis, N assimilation, and protein biosynthesis capacities under drought stress. Overall, our results suggest that melatonin enhances drought stress tolerance in maize through coordinated regulation of C and N metabolism.


Assuntos
Secas , Melatonina , Carbono/metabolismo , Regulação da Expressão Gênica de Plantas , Melatonina/farmacologia , Nitrogênio/metabolismo , Plântula/metabolismo , Estresse Fisiológico , Zea mays/metabolismo
12.
Mater Sci Eng C Mater Biol Appl ; 128: 112328, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474879

RESUMO

Hydrogel-based drug delivery systems have emerged as a promising platform for chronic tissue defects owing to their inherent ability to inhibit pathogenic infection and accelerate rapid tissue regeneration. Here, we fabricated a stable bio-hybrid hydrogel system comprising collagen, aminated xanthan gum, bio-capped silver nanoparticles and melatonin with antimicrobial, antioxidant and anti-inflammatory properties. Highly colloidal bio-capped silver nanoparticles were synthesized using collagen as a reducing cum stabilizing agent for the first time while aminated xanthan gum was synthesized using ethylenediamine treatment on xanthan gum. The synthesized bio-hybrid hydrogel exhibits better gelation, surface morphology, rheology and degelation properties. In vitro assessment of bio-hybrid hydrogel demonstrates excellent bactericidal efficiency against both common wound and multidrug-resistant pathogens and biocompatibility properties. In vivo animal studies demonstrate rapid tissue regeneration, collagen deposition and angiogenesis at the wound site predominantly due to the synergistic effect of silver nanoparticles and melatonin in the hydrogel. This study paves the way for developing biologically functional bio-nano hydrogel systems for promoting effective care for various ailments, including infected chronic wounds.


Assuntos
Melatonina , Nanopartículas Metálicas , Animais , Antibacterianos/farmacologia , Colágeno , Hidrogéis , Melatonina/farmacologia , Prata/farmacologia
13.
Int J Mol Sci ; 22(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34502344

RESUMO

Osteoblasts and osteoclasts are major cellular components in the bone microenvironment and they play a key role in the bone turnover cycle. Many risk factors interfere with this cycle and contribute to bone-wasting diseases that progressively destroy bone and markedly reduce quality of life. Melatonin (N-acetyl-5-methoxy-tryptamine) has demonstrated intriguing therapeutic potential in the bone microenvironment, with reported effects that include the regulation of bone metabolism, acceleration of osteoblastogenesis, inhibition of osteoclastogenesis and the induction of apoptosis in mature osteoclasts, as well as the suppression of osteolytic bone metastasis. This review aims to shed light on molecular and clinical evidence that points to possibilities of melatonin for the treatment of both osteoporosis and osteolytic bone metastasis. It appears that the therapeutic qualities of melatonin supplementation may enable existing antiresorptive osteoporotic drugs to treat osteolytic metastasis.


Assuntos
Antioxidantes/farmacologia , Neoplasias Ósseas/prevenção & controle , Melatonina/farmacologia , Osteoclastos/efeitos dos fármacos , Osteogênese , Osteoporose/prevenção & controle , Animais , Neoplasias Ósseas/secundário , Humanos , Osteoclastos/citologia , Osteoporose/patologia
14.
Ecotoxicol Environ Saf ; 225: 112783, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544023

RESUMO

Sudan I is one of the industry dyes and widely used in cosmetics, wax agent, solvent and textile. Sudan I has multiple toxicity such as carcinogenicity, mutagenicity, genotoxicity and oxidative damage. However, Sudan I has been illegally used as colorant in food products, triggering worldwide attention about food safety. Nevertheless, the toxicity of Sudan I on reproduction, particularly on oocyte maturation is still unclear. In the present study, using mouse in vivo models, we report the toxicity effects of Sudan I on mouse oocyte. The results reflect that Sudan I exposure disrupts spindle organization and chromosomes alignment as well as cortical actin distribution, thus leading to the failure of polar body extrusion. Based on the transcriptome results, it is found that the exposure of Sudan I leads to the change in expression of 764 genes. Moreover, it's further reflected that the damaging effects of Sudan I are mediated by the destruction of mitochondrial functions, which induces the accumulated ROS to stimulate oxidative stress-induced apoptosis. As an endogenous hormone, melatonin within the ovarian follicle plays function on improving oocyte quality and female reproduction by efficiently suppressing oxidative stress. Moreover, melatonin supplementation also improves oocyte quality and increases fertilization rate during in vitro culture. Consistent with these, we find that in vivo supplementation of melatonin efficaciously suppresses mitochondrial dysfunction and the accompanying apoptosis, thus reverses oocyte meiotic deteriorations. Collectively, our results prove the reproduction toxicity of Sudan I for the exposure of Sudan I reduces the oocyte quality, and demonstrate the protective effects of melatonin against Sudan I-induced meiotic deteriorations.


Assuntos
Melatonina , Animais , Apoptose , Feminino , Meiose , Melatonina/metabolismo , Melatonina/farmacologia , Camundongos , Mitocôndrias , Naftóis , Oócitos/metabolismo , Estresse Oxidativo
15.
Molecules ; 26(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34500550

RESUMO

Global warming is impacting the growth and development of economically important but sensitive crops, such as soybean (Glycine max L.). Using pleiotropic signaling molecules, melatonin can relieve the negative effects of high temperature by enhancing plant growth and development as well as modulating the defense system against abiotic stresses. However, less is known about how melatonin regulates the phytohormones and polyamines during heat stress. Our results showed that high temperature significantly increased ROS and decreased photosynthesis efficiency in soybean plants. Conversely, pretreatment with melatonin increased plant growth and photosynthetic pigments (chl a and chl b) and reduced oxidative stress via scavenging hydrogen peroxide and superoxide and reducing the MDA and electrolyte leakage contents. The inherent stress defense responses were further strengthened by the enhanced activities of antioxidants and upregulation of the expression of ascorbate-glutathione cycle genes. Melatonin mitigates heat stress by increasing several biochemicals (phenolics, flavonoids, and proline), as well as the endogenous melatonin and polyamines (spermine, spermidine, and putrescine). Furthermore, the positive effects of melatonin treatment also correlated with a reduced abscisic acid content, down-regulation of the gmNCED3, and up-regulation of catabolic genes (CYP707A1 and CYP707A2) during heat stress. Contrarily, an increase in salicylic acid and up-regulated expression of the defense-related gene PAL2 were revealed. In addition, melatonin induced the expression of heat shock protein 90 (gmHsp90) and heat shock transcription factor (gmHsfA2), suggesting promotion of ROS detoxification via the hydrogen peroxide-mediated signaling pathway. In conclusion, exogenous melatonin improves the thermotolerance of soybean plants and enhances plant growth and development by activating antioxidant defense mechanisms, interacting with plant hormones, and reprogramming the biochemical metabolism.


Assuntos
Antioxidantes/metabolismo , Homeostase/efeitos dos fármacos , Melatonina/farmacologia , Oxirredução/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Poliaminas/metabolismo , Plântula/efeitos dos fármacos , Soja/efeitos dos fármacos , Termotolerância/efeitos dos fármacos , Ácido Abscísico/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Glutationa/metabolismo , Resposta ao Choque Térmico/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/metabolismo , Plântula/metabolismo , Transdução de Sinais/efeitos dos fármacos , Soja/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
16.
Int J Mol Sci ; 22(18)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34575874

RESUMO

Intestinal injury caused by ionizing radiation (IR) is a main clinical issue for patients with cancer receiving abdominal or pelvic radiotherapy. Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that the pineal gland in the brain normally secretes. The study aimed to disclose the potential function of melatonin in intestinal injury induced by IR and its mechanism. Pretreatment with melatonin enhanced the 30-day survival rate of the irradiated mice and promoted the recovery of the intestinal epithelium and hematopoietic function following abdominal irradiation (ABI). Melatonin altered the gene profile of the small intestines from mice following ABI. The enriched biological process terms for melatonin treatment prior to radiation were mainly involved in the immune process. LPS/IL-1-mediated inhibition of RXR Function, TWEAK signaling, and Toll-like receptor signaling were the most activated canonical pathways targeted by melatonin. An upstream analysis network showed that Tripartite motif-containing 24 (TRIM24) was the most significantly inhibited and S100 calcium binding protein A9 (S100A9) activated. TRIM24 activated atherogenesis and cell viability in breast cancer cell lines and S100A9 inhibited the metabolism of amino acids. Melatonin has radioprotective effects on ABI-caused intestinal injury. The mechanisms behind the beneficial effects of melatonin were involved in activation of the immunity. It is necessary to conduct further experiments to explore the underlying mechanisms.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Transporte/genética , Intestinos/lesões , Melatonina/farmacologia , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Abdome/efeitos da radiação , Animais , Calgranulina B/metabolismo , Proteínas de Transporte/metabolismo , Sobrevivência Celular , Citocina TWEAK/metabolismo , Dano ao DNA/efeitos da radiação , Feminino , Raios gama/efeitos adversos , Hematopoese/efeitos da radiação , Humanos , Linfócitos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Nucleares/metabolismo , Fenótipo , Lesões Experimentais por Radiação/tratamento farmacológico , Radiação Ionizante , Receptores X de Retinoides/metabolismo , Fatores de Transcrição/metabolismo , Irradiação Corporal Total
17.
Bioelectromagnetics ; 42(8): 616-628, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34516671

RESUMO

Pulsed electromagnetic field (PEMF) therapy and melatonin (MEL) supplementation are expected to be important strategies for the treatment of osteoporosis. The aim of the current study was to investigate the efficacy of PEMF therapy, MEL supplementation, a combination of PEMF therapy, and MEL supplementation (PEMF + MEL) in mice with bilateral ovariectomy (OVX)-induced osteoporosis. Forty 12-week-old female C57/BL mice were randomly assigned to five groups (n = 8/group): OVX, PEMF, MEL, PEMF + MEL, and sham-operation (sham) groups. All mice in the first four groups were subjected to OVX. The mice in the PEMF and PEMF + MEL groups were exposed to PEMF (75 Hz, 1.6 mT, 1 h/day for 12 weeks), while those in the MEL and PEMF + MEL groups were administered MEL (50 mg/kg, i.p.). Body mass, micro-computed tomography, histology, immunohistochemistry, and real-time polymerase chain reaction were performed. PEMF + MEL treatment enhanced bone volume fraction (BV/TV) 2.2-fold over OVX control (P < 0.001) and increased expression levels of collagen type I (COL1) 1.9-fold and bone morphogenetic protein 2 (BMP2) 2.5-fold. PEMF + MEL also reduced the ratio of bone surface/bone volume (BS/BV) by 40% (P < 0.05) and appeared to reduce the number of osteoclasts in the metaphysis area. Preservation of bone value and bone microarchitecture in the combined therapy group were found to be superior to those in the single treatment groups. However, there were no apparent differences between the PEMF and MEL groups. The use of a combination of PEMF therapy and MEL supplementation may be an effective method to treat osteoporosis. © 2021 Bioelectromagnetics Society.


Assuntos
Campos Eletromagnéticos , Melatonina , Animais , Feminino , Humanos , Melatonina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia , Microtomografia por Raio-X
18.
Physiol Plant ; 173(4): 2041-2054, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34487361

RESUMO

Pot experiments were performed to study the effects of abscisic acid (ABA) and melatonin (MT) on cotton drought tolerance and to explore their combined effects. ABA or MT spraying promoted water status and antioxidant capacity of drought-stressed leaves, which was conducive to scavenge ROS, finally increasing lint yield. However, the mitigation mechanisms of ABA and MT on drought were not identical, which were mainly manifested as: (1) ABA increased the relative water content (RWC) of drought-stressed leaves via, reducing water loss, but MT increased it via, promoting water uptake efficiency; (2) for enzymatic antioxidant system, ABA and MT might modulate different kinds of superoxide dismutase to catalyze the reduction of O2 - under drought; and (3) for ascorbic acid (AsA)-glutathione (GSH) cycle, MT increased the glutathione reductase activity in drought-stressed leaves, but ABA did not. ABA + MT spraying led to higher leaf RWC and total antioxidant capacity than single hormone under drought, leading to a lower H2 O2 level. For the enzymatic antioxidant system, single hormone treatment affected Cu/ZnSOD or MnSOD expression, but ABA + MT upregulated both genes in drought-stressed leaves. Hormones combined application also had higher CAT expression than single hormone. For AsA-GSH cycle, ABA + MT had higher dehydroascorbic acid reductase activity than single hormone, resulting in higher AsA content. Moreover, hormones combined application caused higher ascorbate peroxidase activity than single hormone, suggesting that their combination synergistically improved the ability of AsA to eliminate ROS. All these confirmed that ABA plus MT had synergistic effects on improving crop drought resistance.


Assuntos
Ácido Abscísico , Melatonina , Secas , Gossypium , Melatonina/farmacologia , Folhas de Planta
19.
Theriogenology ; 176: 18-25, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34564013

RESUMO

The objective of this study was to evaluate extender supplemented with melatonin and freezing curves on the antioxidant enzyme activity, peroxidation lipid and sperm characteristics of cryopreserved Brycon orbignyanus milt. Males (n = 16) and females (n = 5) were hormonally induced with two doses (0.5 mg and 5.0 mg kg-1) of carp pituitary extract, and their gametes were collected by light abdominal massage. The fresh milt was diluted at a ratio of 1:4 (milt:extender) in the following solutions: (Control) 10% methyl glycol (MG) + 5% Beltsville thawing solution; (M1) Control + 1 mM melatonin; and (M2) Control + 2 mM melatonin. The freezing curves were C1 (automated freezer) and C2 (dry shipper for 24 h). After each curve was recorded, the straws were transferred to a liquid nitrogen container until the analyses were performed. The samples were thawed in a water bath (60 °C, 8 s) and evaluated using the Sperm Class Analyzer software for the parameters total motility, progressive motility, curvilinear velocity, straight line velocity, mean displacement velocity, straightness, and linearity. The following were also measured: motility time, vitality, morphology, oxidative stress (lipid peroxidation, activity of catalase and superoxide dismutase, quantification of nitric oxide), and fertilization and hatching rates. The data were analyzed within R by one-way analysis of variance and Tukey's test for comparison of means (p < 0.05). A significant difference (p < 0.05) was observed between the solutions in vitality, morphology, motility, and fertilization rate, the solutions with melatonin having the best values. Total motility, progressive motility, and motility time were significantly different. Among oxidative stress markers, only lipid peroxidation and superoxide dismutase activity showed an effect of the curve × solution interaction (p < 0.05), the solutions with melatonin yielding the lowest values. The fertilization and hatching rates were also higher under the melatonin treatments, regardless of the curve. Melatonin 2 mM and slow curve are indicated for the cryopreservation of fish species sperm as it led to the slowest detrimental spermatozoa effects and better fertilization and hatching rates.


Assuntos
Caraciformes , Melatonina , Preservação do Sêmen , Animais , Antioxidantes , Criopreservação/veterinária , Crioprotetores/farmacologia , Feminino , Congelamento , Peroxidação de Lipídeos , Lipídeos , Masculino , Melatonina/farmacologia , Preservação do Sêmen/veterinária , Motilidade Espermática , Espermatozoides
20.
Theriogenology ; 176: 54-62, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34571398

RESUMO

The efficiency of animal artificial breeding in vitro is still low. Oxidative damage is an important obstacle for in vitro artificial breeding of animals. Melatonin can reduce the degree of oxidative damage to both gametes and embryos caused by the external environment. However, there is still some controversy concerning the effect of melatonin on frozen semen, especially in the processes of freezing semen, IVM, IVF and IVC. Here, the effects of melatonin on the whole processes of sperm cryopreservation, oocyte maturation, and embryonic development were studied. The results demonstrated that melatonin at 10-3 M concentration significantly improved progressive sperm viability, plasma membrane integrity, mitochondrial membrane integrity, and acrosome integrity; however, there were also individual differences between bulls, depending on the age of different individuals. The 10-3 M melatonin treatment reduced the reactive oxygen species (ROS) level by nearly 50% in sperm during IVF. Meanwhile, during IVM, the addition of 10-7 M melatonin significantly increased the maturation rate of oocytes and reduced the ROS levels by 58.8%. In addition, 10-7 M melatonin improved the total cell numbers of the IVF blastocysts. Notably, treatment of IVF embryos with melatonin significantly reduced the levels of ROS and influenced the expression levels of key regulatory genes associated with embryo genome activation. This study is of significance for understanding the function of melatonin in animal artificial breeding.


Assuntos
Melatonina , Preservação do Sêmen , Animais , Bovinos , Criopreservação/veterinária , Embrião de Mamíferos , Feminino , Expressão Gênica , Masculino , Melatonina/farmacologia , Gravidez , Sêmen , Preservação do Sêmen/veterinária , Espermatozoides
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