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1.
Clin Exp Reprod Med ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757278

RESUMO

Objective: Scrotal hyperthermia poses a significant threat to spermatogenesis and fertility in mammalian species. This study investigated the effects of vitamin B12 and vitamin C on spermatogenesis in adult male mice subjected to long-term scrotal hyperthermia. The rationale is based on the sensitivity of germ cells and epididymal sperm to increased scrotal temperatures. While various factors, both internal and external, can raise the testicular temperature, this study focused on the potential therapeutic roles of vitamins B12 and C. Methods: After inducing scrotal hyperthermia in mice, vitamin B12 and vitamin C were administered for 35 days. We assessed sperm parameters, serum testosterone levels, stereological parameters, the percentage of apoptotic cells, reactive oxygen species (ROS) levels, and glutathione (GSH) levels. Additionally, real-time polymerase chain reaction was used to analyze the expression of the c-kit, stimulated by retinoic acid gene 8 (Stra8), and proliferating cell nuclear antigen (Pcna) genes. Results: Vitamin C was more effective than vitamin B12 in improving sperm parameters and enhancing stereological parameters. The study showed a significant decrease in apoptotic cells and a beneficial modulation of ROS and GSH levels following vitamin administration. Moreover, both vitamins positively affected the expression levels of the c-kit, Stra8, and Pcna genes. Conclusion: This research deepens our understanding of the combined impact of vitamins B12 and C in mitigating the effects of scrotal hyperthermia, providing insights into potential therapeutic strategies for heat stress-related infertility. The findings highlight the importance of considering vitamin supplementation as a practical approach to counter the detrimental effects of elevated scrotal temperatures on male reproductive health.

2.
Regen Ther ; 27: 506-518, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38745839

RESUMO

Introduction: Acute kidney injury (AKI) is a common health problem that leads to high morbidity and potential mortality. The failure of conventional treatments to improve forms of this condition highlights the need for innovative and effective treatment approaches. Regenerative therapies with Renal Progenitor Cells (RPCs) have been proposed as a promising new strategy. A growing body of evidence suggests that progenitor cells differentiated from different sources, including human embryonic stem cells (hESCs), can effectively treat AKI. Methods: Here, we describe a method for generating RPCs and directed human Embryoid Bodies (EBs) towards CD133+CD24+ renal progenitor cells and evaluate their functional activity in alleviating AKI. Results: The obtained results show that hESCs-derived CD133+CD24+ RPCs can engraft into damaged renal tubules and restore renal function and structure in mice with gentamicin-induced kidney injury, and significantly decrease blood urea nitrogen levels, suppress oxidative stress and inflammation, and attenuate histopathological disturbances, including tubular necrosis, tubular dilation, urinary casts, and interstitial fibrosis. Conclusion: The results suggest that RPCs have a promising regenerative potential in improving renal disease and can lay the foundation for future cell therapy and disease modeling.

3.
Int J Reprod Biomed ; 22(1): 17-30, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38544670

RESUMO

Background: An increase in the temperature of the testis is associated with damage to the epithelium of seminiferous tubules and disruption of sperm production. Objective: The current study aimed to investigate the effect of the Sertoli cell-conditioned medium (SCCM) on the blood-testis-barrier associated genes and spermatogenesis process following scrotal hyperthermia. Materials and Methods: In this experimental study, 40 adult NMRI mice (8 wk, 25-30 gr) were allocated into 4 groups: I) control, II) DMEM (10 µl Dulbecco's Modified Eagle Medium), III) scrotal hyperthermia, and IV) scrotal hyperthermia+SCCM (10 µl SCCM). Hyperthermia was induced by placing the mice scrotum in water at 43 C for 20 min every other day for 10 days. Mice were treated every other day for 5 wk. Then the animals were euthanized, and the tails of epididymis were removed to analyze sperm parameters, testis were taken for stereological assessment, reactive oxygen spices and glutathione levels, and the expression of Ocln, Gja1, Cdh2, and Itgb1. Results: The results of sperm analysis indicated that SCCM-treated mice significantly increased sperm count and motility and reduced DNA fragmentation. In addition, histological and molecular findings showed that the volume of testicular tissue, the number of germ cells, the glutathione level, and the expression of Ocln, Gja1, Cdh2, and Itgb1 genes were significantly increased in the SCCM-treated mice. Conclusion: Findings suggest that growth factors of SCCM stimulate the proliferation and differentiation of germ cells through paracrine effects and upregulate the blood-testis-barrier-associated genes in mice subjected to scrotal hyperthermia.

4.
J Chem Neuroanat ; 137: 102399, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38401660

RESUMO

Cerebellar ataxia (CA) is a condition in which cerebellar dysfunction results in movement disorders such as dysmetria, synergy and dysdiadochokinesia. This study investigates the therapeutic effects of elderberry (EB) diet on the 3-acetylpyridine-induced (3-AP) CA rat model. First, CA rat models were generated by 3-AP administration followed by elderberry diet treatment containing 2 % EB for 8 consecutive weeks. Motor performance, electromyographic activity and gene expression were then evaluated. The number of Purkinje neurons were evaluated by stereological methods. Immunohistochemistry for the microgliosis, astrogliosis and apoptosis marker caspase-3 was also performed. In addition, the morphology of microglia and astrocytes was assessed using the Sholl analysis method. The results showed that EB diet administration in a 3-AP ataxia model improved motor coordination, locomotor activity and neuro-muscular function, prevented Purkinje neurons degeneration, increased microglia and astrocyte complexity and reduced cell soma size. Moreover, EB diet administration decreased apoptosis in cerebellum of 3-AP ataxic model. In addition, elderberry diet treatment decreased the expression of inflammatory, apoptotic and necroptotic genes and increased the expression of antioxidant-related genes. The results suggest that the EB diet attenuates 3-AP-induced neuroinflammation leading to cell death and improves motor performance. Thus, the EB diet could be used as a therapeutic procedure for CA due to its neuroprotective effects.


Assuntos
Ataxia Cerebelar , Modelos Animais de Doenças , Piridinas , Animais , Ratos , Ataxia Cerebelar/patologia , Ataxia Cerebelar/metabolismo , Masculino , Morte Celular , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/metabolismo , Células de Purkinje/patologia , Células de Purkinje/metabolismo , Atividade Motora/fisiologia , Dieta , Ratos Wistar , Microglia/metabolismo , Microglia/patologia , Cerebelo/patologia , Cerebelo/metabolismo
6.
Reprod Sci ; 31(5): 1278-1289, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38228974

RESUMO

Concerns have been raised about potentially irreversible brain damage and damage to the neuroendocrine system during development when treating attention-deficit/hyperactivity disorder with lisdexamfetamine (LDX), a norepinephrine dopamine reuptake inhibitor. This study aims to elucidate the potential adverse effects of LDX on the male reproductive system due to its widespread use and potential for abuse. In this study, adult male rats were randomized into control and LDX groups. Thirty milligrams per kilogram LDX was administered orally for 3 weeks. After isolation of epididymal spermatozoa, the rats were euthanized and testicular tissues were collected for stereological and molecular analyses. The LDX group showed a decrease in sperm motility and an increase in DNA fragmentation compared to the control group. There was also a dramatic decrease in testosterone in the LDX group. Testicular expression of caspase-3 and TNF-α was significantly increased in the LDX group. According to our findings, prolonged use of LDX leads to reduced sperm quality. It also induces apoptosis, inflammatory response, and pathological changes in the testicular tissue. What we have observed in this study is noteworthy but requires further investigation, particularly in people who use LDX over a longer period of time.


Assuntos
Apoptose , Dimesilato de Lisdexanfetamina , Motilidade dos Espermatozoides , Espermatozoides , Testículo , Animais , Masculino , Apoptose/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Dimesilato de Lisdexanfetamina/toxicidade , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Motilidade dos Espermatozoides/efeitos dos fármacos , Ratos Sprague-Dawley , Inflamação/induzido quimicamente , Inflamação/patologia , Ratos , Testosterona , Fragmentação do DNA/efeitos dos fármacos , Caspase 3/metabolismo
7.
Ann Anat ; 252: 152185, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37944830

RESUMO

3-acetylpyridine (3-AP) is a neurotoxin that is known to mainly affect the inferior olivary nucleus (ION) in the brain stem. Although several studies have explored the effect of this neurotoxin, still further investigation is required to understand the impact of this toxin on different parts of the brain. In this research, two groups of rats were studied, the 3-AP-treated and the control groups. Behavioral, stereological, and immunohistochemical analyses were performed. The locomotor activity of the 3-AP-treated rats decreased whereas their anxiety levels were higher than in normal controls. Also, memory performance was impaired in animals in the 3-AP group. Microscopic observations showed a decline in the numerical density of neurons in the hippocampus and striatum along with gliosis. Although this toxin is used to affect the ION, it exerts a neurotoxic effect on different brain regions.


Assuntos
Encéfalo , Neurotoxinas , Ratos , Masculino , Animais , Neurotoxinas/toxicidade , Hipocampo , Piridinas/toxicidade
8.
Int J Environ Health Res ; 34(4): 2052-2066, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37204020

RESUMO

We investigated the association between air pollution and changes in ovarian follicles, anti-mullerian hormone (AMH) levels, the occurrence of necroptosis cell death by activation of receptor-interacting protein kinase 3 (RIPK3) and, the activation of mixed lineage kinase domain-like (MLKL) proteins. Forty-two female Wistar rats were divided into three groups of 14 each, which were exposed to real-ambient air, filtered air and purified air (control) in two periods of 3 and 5 months. The results showed that the number of ovarian follicles decreased in the group exposed to real-ambient air versus the control group (P < 0.0001). The trend of age-related AMH changes with respect to exposure to air pollutants was affected and its levels decreased after 3 months of exposure. The MLKL increased in the group exposed to the real-ambient air compared to the control group (P = 0.033). Apparently long-term exposure to air pollution can reduce ovarian reserves.


Assuntos
Poluição do Ar , Reserva Ovariana , Ratos , Animais , Feminino , Proteínas Quinases/metabolismo , Necroptose , Ratos Wistar , Poluição do Ar/efeitos adversos
9.
Reprod Sci ; 31(3): 675-686, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37816991

RESUMO

Recurrent implantation failure (RIF) is a challenging situation for infertility specialists, and its treatment is introduced as a difficult case in the field of assisted reproductive technology (ART). Vitamin D (VD) is one of the supplements that have been suggested to improve the implantation process. In the present study, the effect of VD on the expression and protein levels of VD receptor (VDR), progesterone receptor (PR), prolactin (PRL), insulin-like growth factor binding protein-1 (IGFBP-1), and homeobox protein A10 (HOXA10) in the endometrial cells of unknown RIF women with and without VD deficiency were assessed by qRT-PCR and immunohistochemistry. Twelve women with unknown RIF and VD deficiency (≤ 20 ng/ml) and twelve women with unknown RIF without VD deficiency (≥ 30 ng/ml) from 2021 to 2022 were identified. Endometrial specimens were collected in the mid-luteal stage before treatment or pregnancy. In the group with VD deficiency, oral medication of VD 50,000 units was prescribed for 2 to 3 months and their serum levels of VD were re-measured, then an endometrial biopsy at the same stage of the menstrual cycle was performed. The expression and protein levels of VDR, PR, PRL, IGFBP1, and HOXA10 in RIF patients with VD deficiency were lower than the RIF patients without VD deficiency (P value < 0.05). Our findings suggest that VD can play a key role in the pregnancy process, especially during embryo implantation and decidualization of the endometrial cells.IRCT registration number: IRCT20220528055006N1, Registration date: 2022-10-15, Registration timing: retrospective.


Assuntos
Decídua , Endométrio , Gravidez , Humanos , Feminino , Decídua/metabolismo , Estudos Retrospectivos , Endométrio/metabolismo , Implantação do Embrião , Vitamina D/uso terapêutico
10.
Anat Cell Biol ; 57(1): 70-84, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37994041

RESUMO

Methamphetamine (METH) can potentially disrupt neurotransmitters activities in the central nervous system (CNS) and cause neurotoxicity through various pathways. These pathways include increased production of reactive nitrogen and oxygen species, hypothermia, and induction of mitochondrial apoptosis. In this study, we investigated the long-term effects of METH addiction on the structural changes in the amygdala of postmortem human brains and the involvement of the brain- cAMP response element-binding protein/brain-derived neurotrophic factor (CREB/BDNF) and Akt-1/GSK3 signaling pathways. We examined ten male postmortem brains, comparing control subjects with chronic METH users, using immunohistochemistry, real-time polymerase chain reaction (to measure levels of CREB, BDNF, Akt-1, GSK3, and tumor necrosis factor-α [TNF-α]), Tunnel assay, stereology, and assays for reactive oxygen species (ROS), glutathione disulfide (GSSG), and glutathione peroxidase (GPX). The findings revealed that METH significantly reduced the expression of BDNF, CREB, Akt-1, and GPX while increasing the levels of GSSG, ROS, RIPK3, GSK3, and TNF-α. Furthermore, METH-induced inflammation and neurodegeneration in the amygdala, with ROS production mediated by the CREB/BDNF and Akt-1/GSK3 signaling pathways.

11.
Toxicol Res (Camb) ; 12(6): 1063-1076, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38145093

RESUMO

This study evaluates whether elderberry (EB) effectively decreases the inflammation and oxidative stress in the brain cells to reduce Aß toxicity. In the Aß + EB group, EB powder was added to rats' routine diet for eight consecutive weeks. Then, spatial memory, working memory, and long-term memory, were measured using the Morris water maze, T-maze, and passive avoidance test. Also, in this investigation immunohistopathology, distribution of hippocampal cells, and gene expression was carried out. Voronoi tessellation method was used to estimate the spatial distribution of the cells in the hippocampus. In addition to improving the memory functions of rats with Aß toxicity, a reduction in astrogliosis and astrocytes process length and the number of branches and intersections distal to the soma was observed in their hippocampus compared to the control group. Further analysis indicated that the EB diet decreased the caspase-3 expression in the hippocampus of rats with Aß toxicity. Also, EB protected hippocampal pyramidal neurons against Aß toxicity and improved the spatial distribution of the hippocampal neurons. Moreover, EB decreased the expression of inflammatory and apoptotic genes. Overall, our study suggest that EB can be considered a potent modifier of astrocytes' reactivation and inflammatory responses.

12.
Toxicol Res (Camb) ; 12(6): 1077-1094, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38145099

RESUMO

The present study aimed to elucidate the effect of 10 mg/kg Δ9-tetrahydrocannabinol (THC) on cerebellar neuronal and glial morphology, apoptosis and inflammatory gene expression using a series of histological assays including stereology, Sholl analysis, immunofluorescence and real-time qPCR in male Wistar rats. A decrease in the number of Purkinje neurons and the thickness of the granular layer in the cerebellum was reported in THC-treated rats. Increased expression of Iba-1 and arborization of microglial processes were evidence of microgliosis and morphological changes in microglia. In addition, astrogliosis and changes in astrocyte morphology were other findings associated with THC administration. THC also led to an increase in caspase-3 positive cells and a decrease in autophagy and inflammatory gene expression such as mTOR, BECN1 and LAMP2. However, there were no significant changes in the volume of molecular layers and white matter, the spatial arrangement of granular layers and white matter, or the spatial arrangement of granular layers and white matter in the cerebellum. Taken together, our data showed both neuroprotective and neurodegenerative properties of THC in the cerebellum, which require further study in the future.

13.
Clin Exp Reprod Med ; 50(4): 230-243, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37995751

RESUMO

OBJECTIVE: High temperatures can trigger cellular oxidative stress and disrupt spermatogenesis, potentially leading to male infertility. We investigated the effects of retinoic acid (RA), chitosan nanoparticles (CHNPs), and retinoic acid loaded with chitosan nanoparticles (RACHNPs) on spermatogenesis in mice induced by scrotal hyperthermia (Hyp). METHODS: Thirty mice (weighing 25 to 30 g) were divided into five experimental groups of six mice each. The groups were as follows: control, Hyp induced by a water bath (43 °C for 30 minutes/day for 5 weeks), Hyp+RA (2 mg/kg/day), Hyp+CHNPs (2 mg/kg/72 hours), and Hyp+RACHNPs (4 mg/kg/72 hours). The mice were treated for 35 days. After the experimental treatments, the animals were euthanized. Sperm samples were collected for analysis of sperm parameters, and blood serum was isolated for testosterone measurement. Testis samples were also collected for histopathology assessment, reactive oxygen species (ROS) evaluation, and RNA extraction, which was done to compare the expression levels of the bax, bcl2, p53, Fas, and FasL genes among groups. Additionally, immunohistochemical staining was performed. RESULTS: Treatment with RACHNPs significantly increased stereological parameters such as testicular volume, seminiferous tubule length, and testicular cell count. Additionally, it increased testosterone concentration and improved sperm parameters. We observed significant decreases in ROS production and caspase-3 immunostaining in the RACHNP group. Moreover, the expression levels of bax, p53, Fas, and FasL significantly decreased in the groups treated with RACHNPs and RA. CONCLUSION: RACHNPs can be considered a potent antioxidative and antiapoptotic agent for therapeutic strategies in reproductive and regenerative medicine.

14.
Toxicol Res (Camb) ; 12(5): 783-795, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37915479

RESUMO

The present study was designed to evaluate whether elderberry (EB) effectively reduces inflammation and oxidative stress in hippocampal cells to modify seizure damage. Seizure was induced in rats by the injection of pentylenetetrazol (PTZ). In the Seizure + EB group, EB powder was added to the rats' routine diet for eight consecutive weeks. The study included several behavioral tests, immunohistopathology, Voronoi tessellation (to estimate the spatial distribution of cells in the hippocampus), and Sholl analysis. The results in the Seizure + EB group showed an improvement in the behavioral aspects of the study, a reduction in astrogliosis, astrocyte process length, number of branches, and intersections distal to the soma in the hippocampus of rats compared to controls. Further analysis showed that EB diet increased nuclear factor-like 2 expression and decreased caspase-3 expression in the hippocampus in the Seizure + EB group. In addition, EB protected hippocampal pyramidal neurons from PTZ toxicity and improved the spatial distribution of hippocampal neurons in the pyramidal layer and dentate gyrus. The results of the present study suggest that EB can be considered a potent modifier of astrocyte reactivation and inflammatory responses.

15.
Metab Brain Dis ; 38(8): 2735-2750, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37851137

RESUMO

Epilepsy significantly reduces the patient's quality of life, and we still need to develop new therapeutic approaches to control it. Transplantation of cells such as Sertoli cells (SCs), having a potent ability to release a variety of growth and immunoprotective substances, have made them a potential candidate to deal with neurological diseases like epilepsy. Hence, this study aims to evaluate whether SCs transplant effectively protects the hippocampus astrocytes and neurons to oppose seizure damage. For this purpose, the effects of bilateral intrahippocampal transplantation of SCs were investigated on the rats with the pentylenetetrazol (PTZ) induced seizure. After one-month, post-graft analysis was performed regarding behavior, immunohistopathology, and the distribution of the hippocampal cells. Our findings showed SCs transplantation reduced astrogliosis, astrocytes process length, the number of branches, and intersections distal to the soma of the hippocampus in the seizure group. In rats with grafted SCs, there was a drop in the hippocampal caspase-3 expression. Moreover, the SCs showed another protective impact, as shown by an improvement in pyramidal neurons' number and spatial distribution. The findings suggested that SCs transplantation can potently modify astrocytes' reactivation and inflammatory responses.


Assuntos
Epilepsia , Células de Sertoli , Masculino , Ratos , Humanos , Animais , Células de Sertoli/patologia , Qualidade de Vida , Convulsões/tratamento farmacológico , Epilepsia/tratamento farmacológico , Hipocampo/metabolismo , Morte Celular , Amnésia/metabolismo
16.
PLoS One ; 18(10): e0291757, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37788257

RESUMO

Accurate evaluation of morphological changes in articular cartilage are necessary for early detection of osteoarthritis (OA). 3T magnetic resonance imaging (MRI) has highly sensitive contrast resolution and is widely used clinically to detect OA. However, synchrotron radiation phase-contrast imaging computed tomography (SR-PCI) can also provide contrast to tissue interfaces that do not have sufficient absorption differences, with the added benefit of very high spatial resolution. Here, MRI was compared with SR-PCI for quantitative evaluation of human articular cartilage. Medial tibial condyles were harvested from non-OA donors and from OA patients receiving knee replacement surgery. Both imaging methods revealed that average cartilage thickness and cartilage volume were significantly reduced in the OA group, compared to the non-OA group. When comparing modalities, the superior resolution of SR-PCI enabled more precise mapping of the cartilage surface relative to MRI. As a result, MRI showed significantly higher average cartilage thickness and cartilage volume, compared to SR-PCI. These data highlight the potential for high-resolution imaging of articular cartilage using SR-PCI as a solution for early OA diagnosis. Recognizing current limitations of using a synchrotron for clinical imaging, we discuss its nascent utility for preclinical models, particularly longitudinal studies of live animal models of OA.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Intervenção Coronária Percutânea , Animais , Humanos , Cartilagem Articular/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Síncrotrons , Imageamento por Ressonância Magnética/métodos , Articulação do Joelho/diagnóstico por imagem
17.
Metab Brain Dis ; 38(8): 2679-2690, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37831362

RESUMO

BACKGROUND: The choroid plexus (CP) is the principal source of cerebrospinal fluid (CSF). It can produce and release a wide range of materials, including growth and neurotrophic factors which have a crucial role in the maintenance and proper functioning of the brain. Tramadol is a synthetic analog of codeine, mainly prescribed to alleviate mild to moderate pains. Nevertheless, it causes several side effects, such as emotional instability and anxiety. METHODS: In this study, we focused on alterations in the expression of inflammatory and apoptotic genes in the CP under chronic tramadol exposure. Herein, rats were treated daily with tramadol at 50 mg/kg doses for three weeks. CSF samples were collected, with superoxide dismutase (SOD) and glutathione (GSH) measured in the CSF. RESULTS: We found that tramadol reduced the SOD and GSH levels in the CSF. Furthermore, the stereological analysis revealed a significant increase in the CP volume, epithelial cells, and capillary number upon tramadol administration. Tramadol elevated the number of blob mitochondria in CP. Also, we observed the upregulation of inflammatory and apoptosis genes following tramadol administration in the CP. CONCLUSIONS: Our findings indicate that tramadol induces neurotoxicity in the CP via apoptosis, inflammation, and oxidative stress.


Assuntos
Tramadol , Ratos , Animais , Tramadol/farmacologia , Plexo Corióideo/metabolismo , Estresse Oxidativo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Glutationa/metabolismo , Apoptose , Superóxido Dismutase/metabolismo
18.
Inflammation ; 46(5): 1966-1980, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37310644

RESUMO

Acetyl-11-keto-beta-boswellic acid (AKBA), a potent anti-inflammatory compound purified from Boswellia species, was investigated in a preclinical study for its potential in preventing and treating non-alcoholic fatty liver disease (NAFLD), the most common chronic inflammatory liver disorder. The study involved thirty-six male Wistar rats, equally divided into prevention and treatment groups. In the prevention group, rats were given a high fructose diet (HFrD) and treated with AKBA for 6 weeks, while in the treatment group, rats were fed HFrD for 6 weeks and then given a normal diet with AKBA for 2 weeks. At the end of the study, various parameters were analyzed including liver tissues and serum levels of insulin, leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-ß), interferon gamma (INF-ϒ), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). Additionally, the expression levels of genes related to the inflammasome complex and peroxisome proliferator-activated receptor gamma (PPAR-ϒ), as well as the levels of phosphorylated and non-phosphorylated AMP-activated protein kinase alpha-1 (AMPK-α1) protein, were measured. The results showed that AKBA improved NAFLD-related serum parameters and inflammatory markers and suppressed PPAR-ϒ and inflammasome complex-related genes involved in hepatic steatosis in both groups. Additionally, AKBA prevented the reduction of the active and inactive forms of AMPK-α1 in the prevention group, which is a cellular energy regulator that helps suppress NAFLD progression. In conclusion, AKBA has a beneficial effect on preventing and avoiding the progression of NAFLD by preserving lipid metabolism, improving hepatic steatosis, and suppressing liver inflammation.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Ratos , Masculino , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Inflamassomos/metabolismo , Frutose/metabolismo , Frutose/farmacologia , Frutose/uso terapêutico , Metabolismo dos Lipídeos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Ratos Wistar , Fígado/metabolismo , Dieta , Inflamação/metabolismo
19.
Basic Clin Androl ; 33(1): 13, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37226085

RESUMO

BACKGROUND: Obesity is regarded a global public health crisis. It has been implicated in a variety of health problems, but when it comes to male fertility, how and to what extent obesity affects it are poorly understood. Accordingly, semen samples from 32 individuals with obesity (body mass index (BMI) ≥ 30 kg/m2) and 32 individuals with normal weight (BMI: 18.5-25 kg/m2) were obtained. Here, for the first time, we examined the association between obesity, relative sperm telomere length (STL) and autophagy-related mRNA levels such as Beclin1, AMPKa1, ULK1, BAX, and BCL2. Each group was also evaluated for conventional semen parameters, sperm apoptotic changes, DNA fragmentation index (DFI), sperm chromatin maturation, and reactive oxygen species (ROS) levels. RESULTS: Based on our findings, there was a marked reduction in relative STL in individuals with obesity as compared to the normal-weight group. We also found a significant negative correlation between relative STL and age, BMI, DFI, percentage of sperm with immature chromatin, and intracellular ROS levels in patients with obesity. In the normal-weight group, relative STL was only negatively correlated with DFI and intracellular ROS levels. Regarding mRNA expression, there was considerable upregulation of Beclin1, ULK1, and BCL2 in the group with obesity compared to the normal-weight group. Obesity was also found to be associated with a considerable decline in semen volume, total sperm count, progressive motility, and viability in comparison to normal-weight individuals. Furthermore, obesity was associated with considerably higher percentages of DFI, sperm with immature chromatin, late-stage apoptosis, and elevated ROS levels. CONCLUSION: According to our findings, obesity is associated with sperm telomere shortening and aberrant autophagy-related mRNA expression. It should be emphasized that telomere shortening in sperm may be an indirect consequence of obesity due to the oxidative stress associated with the condition. Nevertheless, further investigation is required for a more comprehensive understanding.


RéSUMé: CONTEXTE: L'obésité est considérée comme une crise mondiale de santé publique. Elle a été impliquée dans divers problèmes de santé ; mais quand il s'agit de la fertilité masculine, comment et dans quelle mesure l'obésité affecte cette fertilité restent mal compris. En conséquence, des échantillons de sperme de 32 hommes obèses (indice de masse corporelle (IMC) ≥ 30 kg/m²) et de 32 hommes ayant un poids normal (IMC : 18,5 à 25 kg/m²) ont été recueillis. A été examiné dans cette étude, pour la première fois, l'association entre l'obésité, la longueur relative des télomères des spermatozoïdes (LTS), et les taux d'ARNm liés à l'autophagie tels que Beclin1, AMPKa1, ULK1, BAX et BCL2. Chaque groupe a également été évalué pour les paramètres conventionnels du sperme, les changements apoptotiques des spermatozoïdes, l'indice de fragmentation de l'ADN (DFI), la maturation de la chromatine des spermatozoïdes et les niveaux d'espèces réactives de l'oxygène (ROS). RéSULTATS: Il y eut une réduction marquée de la LTS relative chez les hommes obèses par rapport à ceux du groupe de poids normal. Nous avons également trouvé une corrélation négative significative entre la LTS relative et l'âge, l'IMC, le DFI, le pourcentage de spermatozoïdes avec chromatine immature et les niveaux intracellulaires de ROS chez les hommes obèses. Dans le groupe d'hommes de poids normal, la LTS relative n'était corrélée négativement qu'avec les taux de DFI et de ROS intracellulaires. En ce qui concerne l'expression de l'ARNm, il y avait une régulation positive considérable de Beclin1, ULK1 et BCL2 dans le groupe d'hommes obèses par rapport à ceux du  groupe de poids normal. L'obésité s'est également avérée être associée à une baisse considérable du volume de sperme, du nombre total de spermatozoïdes, de la mobilité progressive et de la viabilité des spermatozoïdes par rapport aux hommes de poids normal. En outre, l'obésité était associée à des pourcentages considérablement plus élevés de DFI, de spermatozoïdes avec chromatine immature, d'apoptose à un stade avancé, et de niveaux élevés de ROS. CONCLUSION: Selon nos résultats, l'obésité est associée au raccourcissement des télomères des spermatozoïdes et à une expression aberrante d'ARNm liés à l'autophagie. Il convient de souligner que le raccourcissement des télomères dans les spermatozoïdes peut être une conséquence indirecte de l'obésité en raison du stress oxydatif associé à la maladie. Néanmoins, des études plus approfondies sont nécessaires pour une compréhension plus complète.

20.
Lasers Med Sci ; 38(1): 114, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37103593

RESUMO

Testicular heat stress leads to impairment of spermatogenesis in mammals. Involved mechanism in this vulnerability to heat-induced injury remains unclear, and research is being conducted to find an approach to reverse spermatogenesis arrest caused by hyperthermia. Recently, different studies have utilized photobiomodulation therapy (PBMT) therapy for the improvement of sperm criteria and fertility. This study aimed at evaluating the effect of PBMT on the improvement of spermatogenesis in mouse models of hyperthermia-induced azoospermia. A total of 32 male NMRI mice were equally divided into four groups consisting of control, hyperthermia, hyperthermia + Laser 0.03 J/cm2, and hyperthermia + Laser 0.2 J/cm2. To induce scrotal hyperthermia, mice were anesthetized and placed in a hot water bath at 43 °C for 20 min for 5 weeks. Then, PBMT was operated for 21 days using 0.03 J/cm2 and 0.2 J/cm2 laser energy densities in the Laser 0.03 and Laser 0.2 groups, respectively. Results revealed that PBMT with lower intensity (0.03 J/cm2) increased succinate dehydrogenase (SDH) activity and glutathione (GSH)/oxidized glutathione (GSSG) ratio in hyperthermia-induced azoospermia mice. At the same time, low-level PBMT reduced reactive oxygen species (ROS), mitochondrial membrane potential, and lipid peroxidation levels in the azoospermia model. These alterations accompanied the restoration of spermatogenesis manifested by the elevated number of testicular cells, increased volume and length of seminiferous tubules, and production of mature spermatozoa. After conducting experiments and analyzing the results, it has been revealed that the use of PBMT at a dosage of 0.03 J/cm2 has shown remarkable healing effects in the heat-induced azoospermia mouse model.


Assuntos
Azoospermia , Hipertermia Induzida , Terapia com Luz de Baixa Intensidade , Humanos , Masculino , Camundongos , Animais , Azoospermia/etiologia , Azoospermia/radioterapia , Terapia com Luz de Baixa Intensidade/métodos , Temperatura Alta , Sêmen , Testículo , Glutationa , Mamíferos
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