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Kisspeptin is an endogenous peptide hormone that is the most potent stimulator of the hypothalamo-pituitary-gonadal (HPG) axis. The HPG axis can be suppressed by the activation of the hypothalamo-pituitary-adrenal (HPA) axis. The physiological role of kisspeptin in the interaction of the HPG axis and the HPA axis is not fully understood yet. The purpose of the current study was to investigate the possible effects of peripheral injection (intraperitoneally) of kisspeptin on HPG axis and HPA axis activity as well. Adult male Wistar rats were randomly divided into seven groups as sham (control), kisspeptin (10 nmol), p234 (10 nmol), kisspeptin + p234, kisspeptin + antalarmin (10 mg/kg), kisspeptin + astressin2b (100 µg/kg), and kisspeptin + atosiban (0.250 mg/kg) (n = 10 each group). At the end of the experiment, the hypothalamus, pituitary gland, and serum samples of the rats were collected. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin and kisspeptin + astressin2b groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin, kisspeptin + antalarmin, kisspeptin + astressin2b, and kisspeptin + atosiban groups that compared to the control group. There was no a significant difference in corticotropic releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone and corticosterone concentrations among all groups. Moreover, no significant difference was found in the concentration of pituitary oxytocin. Our results suggest that peripheral kisspeptin injection induces an activation in the HPG axis, but not in the HPA axis in male rats.
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Microglia are immune cells that play important roles in the formation of the innate immune response within the central nervous system (CNS). The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiple protein complex that is crucial for innate immunity, and excessive activation of the inflammasome for various reasons contributes to the pathogenesis of neurodegenerative diseases (NDs). ß2-adrenoceptor agonists have become the focus of attention in studies on NDs due to the high synthesis of ß2-adrenoceptors in the central nervous system (CNS). Promising results have been obtained from these studies targeting anti-inflammatory and neuroprotective effects. Formoterol is an effective, safe for long-term use, and FDA-approved ß2-adrenoceptor agonist with demonstrated anti-inflammatory features in the CNS. In this study, we researched the effects of formoterol on LPS/ATP-stimulated NLRP3 inflammasome activation, pyroptosis, NF-κB, autophagy, and ESCRT-III-mediated plasma membrane repair pathways in the N9 microglia cells. The results showed that formoterol, through the IκBα/NF-κB axis, significantly inhibited NLRP3 inflammasome activation, reduced the level of active caspase-1, secretion of IL-1ß and IL-18 proinflammatory cytokine levels, and the levels of pyroptosis. Additionally, we showed that formoterol activates autophagy, autophagosome formation, and ESCRT-III-mediated plasma membrane repair, which are significant pathways in the inhibition of NLRP3 inflammasome activation and pyroptosis. Our study suggests that formoterol efficaciously prevents the NLRP3 inflammasome activation and pyroptosis in microglial cells regulation through IκBα/NF-κB, autophagy, autophagosome formation, and ESCRT-III-mediated plasma membrane repair.
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Agonistas de Receptores Adrenérgicos beta 2 , Autofagia , Fumarato de Formoterol , Inflamasomas , Microglía , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Animales , Piroptosis/efectos de los fármacos , Ratones , FN-kappa B/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Autofagia/efectos de los fármacos , Fumarato de Formoterol/farmacología , Agonistas de Receptores Adrenérgicos beta 2/farmacología , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Inhibidor NF-kappaB alfa/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Línea CelularRESUMEN
PURPOSE: We aimed to examine the effectiveness of mother milk exosomes in treating corrosive esophageal burns. MATERIALS AND METHODS: 32 rats were separated into four equal groups and weighed individually before the procedure. A corrosive esophageal burn model was created with 12.5% sodium hydroxide by a 3F Fogarty catheter. Group 1 did not apply any process or treatment, Group 2 was burned, and no treatment was performed. Group 3 was burned, and then 0.5 cc/day of mother milk exosome extract was given. Group 4 was not applied any process, and 0.5 cc/day mother milk exosome extract was given. All rats were weighed again and sacrificed. Biopsy samples were sent to the pathology laboratory for histopathological examination (in terms of inflammation, fibrosis, and necrosis).Kindly check and confrm all email ids.The e-mail addresses and affiliation of all authors were checked. Affiliation departments are as stated on the title page. There is no change. RESULTS: A significant difference was found in the results of inflammation and fibrosis. There was a meaningful difference in fibrosis between the 2nd and 3rd groups. There was weight gain in groups 1, 3 and 4. Statistical evaluations for each group were significant. CONCLUSION: It was observed that breast milk exosomes may be effective in inflammation and fibrosis formation in treating corrosive esophageal burns. This suggested that breast milk exosomes reduce stricture formation due to esophageal corrosion.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [specify authors given name] Last name [specify authors last name]. Also, kindly confirm the details in the metadata are correct.The names and affiliation of all authors were checked. Affiliation departments are as stated on the title page. There is no change. Also we confirm the details in the metadata.
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Quemaduras Químicas , Modelos Animales de Enfermedad , Exosomas , Animales , Ratas , Quemaduras Químicas/terapia , Esofagitis/inducido químicamente , Esofagitis/patología , Cáusticos/toxicidad , Leche Humana , Femenino , Hidróxido de Sodio/toxicidad , Esófago/patología , MasculinoRESUMEN
Kisspeptin is an important hormone involved in the stimulation of the hypothalamo-pituitary gonadal (HPG) axis. The HPG axis can be suppressed in certain conditions such as stress, which gives rise to the activation of the hypothalamo-pituitary-adrenal (HPA) axis. However, the physiological role of kisspeptin in the interaction of HPG and HPA axis is not fully understood yet. This study was conducted to investigate the possible effects of central kisspeptin injection on HPG axis as well as HPA axis activity. Adult male Wistar rats were randomly divided into seven groups as followed: sham (control), kisspeptin (50 pmol), P234 (1 nmol), kisspeptin + p234, kisspeptin + antalarmin (0.1 µg), kisspeptin + astressin 2B (1 µg), and kisspeptin + atosiban (300 ng/rat) (n = 10 each group). At the end of the experiments, the hypothalamus, pituitary, and serum samples of the rats were collected. There was no significant difference in corticotropic-releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone, and corticosterone levels among all groups. Moreover, no significant difference was detected in pituitary oxytocin level. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin, and kisspeptin + astressin 2B groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin kisspeptin + antalarmin, kisspeptin + astressin 2B, and kisspeptin + atosiban groups compared to the control group. Our findings suggest that central kisspeptin injection causes activation in the HPG axis, but not the HPA axis in male rats.
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Sistema Hipotálamo-Hipofisario , Kisspeptinas , Sistema Hipófiso-Suprarrenal , Ratas Wistar , Animales , Masculino , Kisspeptinas/administración & dosificación , Kisspeptinas/farmacología , Kisspeptinas/metabolismo , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/metabolismo , Ratas , Fragmentos de Péptidos/administración & dosificación , Hormona Luteinizante/sangre , Hormona Luteinizante/metabolismo , Corticosterona/sangre , Vasotocina/farmacología , Vasotocina/administración & dosificación , Testosterona/sangre , Inyecciones Intraventriculares , Gónadas/metabolismo , Gónadas/efectos de los fármacos , Hipófisis/metabolismo , Hipófisis/efectos de los fármacos , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Adrenocorticotrópica/sangre , Hormona Liberadora de Corticotropina , OligopéptidosRESUMEN
The purpose of this study was to investigate the effects of gentamicin (GEN) on the testis and whether quercetin (QUE) has any protective effect. Twenty-four adult male Sprague-Dawley rats were divided into equal four groups: control (0.9% saline solution), GEN (80 mg∕kg GEN), QUE (50 mg∕kg QUE) and GEN+QUE (80 mg∕kg GEN + 50 mg∕kg QUE). Histopathological (HP) evaluation of testis was performed, epididymal sperm parameters were analyzed and oxidative status was evaluated. The use of QUE improved the HP findings, such as decrease in the germinal epithelial thickness in the testicular tissue of the GEN group, decrease in the Johnsen's tubular biopsy score (JTBS), increase in the rate of immature cell shedding tubules, and the apoptotic index (AI). In the GEN group, sperm count, and abnormal morphology increased compared to the control group; the viability and motility decreased according to the sperm analysis results. In the GEN+QUE group, QUE was found to improve sperm viability and morphology. In the GEN group, tissue malondialdehyde (MDA) levels increased while superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels decreased. Compared with the GEN+QUE group, it was found that the tissue MDA level decreased, while the levels of SOD, CAT and GPx increased. The results demonstrate that GEN impairs testicular structure and function, and QUE treatment can prevent this adverse effect.
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Antioxidantes , Quercetina , Ratas , Masculino , Animales , Quercetina/farmacología , Quercetina/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Ratas Sprague-Dawley , Semen/metabolismo , Testículo/patología , Espermatozoides/metabolismo , Espermatozoides/patología , Glutatión Peroxidasa/metabolismo , Glutatión Peroxidasa/farmacología , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/farmacología , Estrés OxidativoRESUMEN
BACKGROUND: Neuroinflammation induced by systemic inflammation is a risk factor for developing chronic neurologic disorders. Oleuropein (OLE) has antioxidant and anti-inflammatory properties; however, its effect on systemic inflammation-related neuroinflammation is unknown. OBJECTIVES: This study aimed to determine whether OLE protects against systemic lipopolysaccharide (LPS)-induced neuroinflammation in rats. METHODS: Six-wk-old Wistar rats were randomly assigned to 1 of the following 5 groups: 1) control, 2) OLE-only, 3) LPS + vehicle, 4) OLE+LPS (O-LPS), and 5) a single-dose OLE + LPS (SO-LPS group). OLE 200 mg/kg or saline as a vehicle was administered via gavage for 7 d. On the seventh day, 2.5 mg/kg LPS was intraperitoneally administered. The rats were decapitated after 24 h of LPS treatment, and serum collection and tissue dissection were performed. The study assessed astrocyte and microglial activation using glial fibrillary acidic protein (GFAP) and CD11b immunohistochemistry, nod-like receptor protein-3, interleukin (IL)-1ß, IL-17A, and IL-4 concentrations in prefrontal and hippocampal tissues via enzyme-linked immunosorbent assay, and total antioxidant/oxidant status (TAS/TOS) in serum and tissues via spectrophotometry. RESULTS: In both the O-LPS and SO-LPS groups, LPS-related activation of microglia and astrocytes was suppressed in the cortex and hippocampus (P < 0.001), excluding cortical astrocyte activation, which was suppressed only in the SO-LPS group (P < 0.001). Hippocampal GFAP immunoreactivity and IL-17A concentrations in the dentate gyrus were higher in the OLE group than those in the control group, but LPS-related increases in these concentrations were suppressed in the O-LPS group. The O-LPS group had higher cortical TAS and IL-4 concentrations. CONCLUSIONS: OLE suppressed LPS-related astrocyte and microglial activation in the hippocampus and cortex. The OLE-induced increase in cortical IL-4 concentrations indicates the induction of an anti-inflammatory phenotype of microglia. OLE may also modulate astrocyte and IL-17A functions, which could explain its opposing effects on hippocampal GFAP immunoreactivity and IL-17A concentrations when administered with or without LPS.
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Interleucina-17 , Glucósidos Iridoides , Lipopolisacáridos , Ratas , Animales , Masculino , Lipopolisacáridos/toxicidad , Ratas Wistar , Interleucina-17/metabolismo , Interleucina-17/farmacología , Interleucina-17/uso terapéutico , Enfermedades Neuroinflamatorias , Antioxidantes/metabolismo , Interleucina-4/metabolismo , Interleucina-4/farmacología , Interleucina-4/uso terapéutico , Hipocampo/metabolismo , Inflamación/metabolismo , Antiinflamatorios/farmacología , Interleucina-1beta/metabolismo , Microglía/metabolismoRESUMEN
BACKGROUND: The effects of housing conditions on animal physiology, behavior or stress are still debated. The aim of this study was to investigate the effects of three different housing systems, individually ventilated cages (IVC), classical small cages with floor surface area of 500 cm2 (CC500) and classical large cages with floor surface area of 800 cm2 (CC800) on body weight, sensory-motor performances, depression-like behavior, plasma corticosterone and brain oxidative stress parameters in C57BL/6 mice. The mice housed in one of the cages from birth to 6 months of age. Hang wire and adhesive removal tests were performed to evaluate somatosensory and motor performances. The extent of depression was determined by the forced swim test. Blood corticosterone levels were measured. In addition, brain malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) levels were analyzed. RESULTS: The depression-like behavior of the groups was similar. Although there were no significant differences in hang wire test among groups, CC500 group required longer durations in adhesive removal test. The body weight and plasma corticosterone levels of CC800 group were significantly higher than other groups. The oxidative stress parameters were highest in CC500 cage. CONCLUSIONS: Our study showed that the least stressful housing condition was IVC cage systems. Interestingly, the number of mice in the classical cages had a significant effect on stress levels and sensory-motor performance.
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BACKGROUND: Carbonic anhydrases (CA) are metalloenzymes with wide tissue distribution, involved in many important physiological processes, and in some rheumatic diseases, autoantibodies are formed against these enzymes. Recent studies have suggested that oxidative stress triggers anti-CA antibody formation. In this study, we aimed to investigate the effects of modification with oxidative/nitrosative stress end products on CA antigenicity in mice and the relationship between the modified CA autoantibodies and oxidant-antioxidant status in patients with rheumatoid arthritis (RA) and Sjögren's syndrome (SjS). METHODS: CA I and CA II isoenzymes were isolated from human erythrocytes and modified with 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and peroxynitrite (PN). Balb-c mice were immunized with these agents to determine the effects of modification on CA antigenicity. The autoantibody titers of modified CA isoenzymes were detected in patients. In addition MDA, 4-HNE, 3-nitrotyrosine (3-NT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities were measured to assess the oxidant-antioxidant status in patients. RESULTS: Modifications of carbonic anhydrase with oxidative stress end products, HNE, MDA and PN, lead to alterations in the immune response to these enzymes in mice. It was found that HNE and MDA decreased the antigenicity while PN increased. In addition, PN-modified CA autoantibody levels were found to be significantly different in both RA and SjS patients compared to their controls (p<0.05). CONCLUSIONS: PN modifications can also trigger an immune response against CA isoenzymes in mice, and PN-modified CA I and CA II autoantibody titers were found at a significantly high level in both RA and SjS patients.
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Artritis Reumatoide , Anhidrasas Carbónicas , Humanos , Animales , Ratones , Ácido Peroxinitroso , Antioxidantes , Isoenzimas , Autoanticuerpos , Estrés Oxidativo , Malondialdehído , Inmunidad , OxidantesRESUMEN
Reports suggest that a highcholesterol diet may induce neuroinflammation, oxidative stress, and neurodegeneration in brain tissue. Brainderived neurotrophic factor (BDNF) might play a role in protecting against changes induced by high cholesterol. We aimed to assess behavioral correlates and biochemical alterations in the motor and sensory cortices following a highcholesterol diet under normal and reduced BDNF concentrations. C57Bl/6 strain, wildtype (WT) and BDNF heterozygous (+/) mice were used to reveal the effects of endogenous BDNF concentrations. We compared diet and genotype effects using four experimental groups: WT and BDNF heterozygous (+/) groups of mice were each fed a normal or highcholesterol diet for 16 weeks. The cylinder test and wire hanging test were performed to evaluate neuromuscular deficits and cortical sensorymotor functions, respectively. In addition, neuroinflammation was assessed by tumor necrosis factor alpha and interleukin 6 levels measured in the somatosensory and motor areas. Additionally, MDA levels and SOD and CAT activity were evaluated as oxidative stress parameters. Results showed that a highcholesterol diet significantly impaired behavioral performance in the BDNF (+/) group. Diet did not change the levels of neuroinflammatory markers in any of the groups. However, MDA levels, an indicator of lipid peroxidation, were significantly higher in the highcholesterolfed BDNF (+/) mice. The results suggest that BDNF levels might be a critical factor in determining the extent of neuronal damage induced in the neocortex by a highcholesterol diet.
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Factor Neurotrófico Derivado del Encéfalo , Enfermedades Neuroinflamatorias , Ratones , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Corteza Cerebral/metabolismo , Estrés Oxidativo , Dieta , Colesterol/farmacologíaRESUMEN
OBJECTIVE: The aim of this randomized controlled study was to investigate the effect of music therapy during restorative dental treatments on patients with moderate dental anxiety. MATERIALS AND METHODS: Seventy patients were determined to have moderate dental anxiety by the Modified Dental Anxiety Scale (MDAS) and were divided randomly into two groups (n = 35). The first group did not listen to music during their restorative treatment (control group), and the second group listened to music of their choice (experimental group). Systolic blood pressure, diastolic blood pressure, heart rate, oxygen saturation, and body temperature were measured three times for each patient: once before the treatment, once after their dental caries were removed, and once at the end of the treatment. Salivary cortisol samples were taken from each patient before and after the treatment. The MDAS was re-administered to the patients at the end of the treatment, and the data were analyzed statistically. RESULTS: Only the diastolic blood pressure (P = 0.042) and the MDAS scores of the experimental group (P = 0.001) were significantly lower than the control group at the end of the treatment. CONCLUSION: While music listening did not have an effect on the physiologic parameters of the patients during restorative treatment, it decreased the MDAS scores of the patients. CLINICAL RELEVANCE: Although music therapy did not affect the physiological parameters during the restorative dental treatment, it may help to reduce patients' self reported anxiety level.
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Caries Dental , Musicoterapia , Música , Humanos , Ansiedad al Tratamiento Odontológico/terapia , Caries Dental/terapia , Ansiedad/terapia , Atención OdontológicaRESUMEN
We aimed to investigate the contribution of irisin in the neuroprotective process of exercise training in diabetic rats. Serum irisin levels, thermal and mechanical pain thresholds and intracellular calcium ([Ca2+]i) levels in sensory neurons were measured at different time intervals during the eight weeks of exercise sessions for the control, non-exercise diabetics (3 groups) and exercise performing (low and high intensity groups) diabetic rats (n = 7-10 for all groups). Non-exercise diabetic groups were treated with irisin in different doses (1, 10 and 20 µg/kg respectively). Recovered pain thresholds at the end of the exercise sessions (p < .05), higher serum irisin levels that compared to control and diabetics (p < .05) and insignificant mean [Ca2+]i peak amplitudes in sensory neurons (p > .05) obtained from experiments. Furthermore, irisin injection decreased the thermal pain threshold of diabetics only at 60th minutes (p < .05). Irisin may have a role in the neuroprotective effect of exercise training.
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Diabetes Mellitus Experimental , Fármacos Neuroprotectores , Condicionamiento Físico Animal , Ratas , Masculino , Animales , Fibronectinas , Fármacos Neuroprotectores/farmacología , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/terapia , Condicionamiento Físico Animal/fisiología , Umbral del DolorRESUMEN
AIMS: Prolonged Endoplasmic Reticulum Stress (ERS) is involved in the pathogenesis of metabolic syndrome, including type-2 diabetes mellitus, cardiovascular diseases, atherosclerosis, obesity, and fatty liver disease. There have been significant efforts to discover molecules to treat ERS and/or to ameliorate associate symptoms. In this study, we investigated the effect of 7,8-Dihydroxyflavone (7,8-DHF) on ERS in liver and pancreas tissues in a cafeteria (CAF) diet induced metabolic syndrome model. MAIN METHODS: Male C57BL/6 mice were fed CAF diet for 16 weeks and 7,8-DHF was administered intraperitoneally (5 mg/kg/day) for last four weeks. 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) in liver and pancreas tissues, insulin and interleukin-1ß (IL-1ß) in serum were analyzed by ELISA method and serum biochemistry parameters were analyzed with autoanalyzer. GRP78 and CHOP gene expression levels were determined by qRT-PCR. In addition, histopathological analyzes were performed on liver and pancreas tissues. KEY FINDINGS: Findings revealed that CAF diet caused metabolic abnormalities, insulin resistance and inflammation in serum and triggered ERS in pancreas and liver tissues. 7,8-DHF treatment significantly reduced metabolic abnormalities by reducing serum biochemical parameters, HOMO-IR and IL-1ß levels. qRT-PCR and ELISA results indicated that 7,8-DHF treatment down-regulated GRP78 and CHOP expression and protein levels in the liver and GRP78 expression in pancreas. Efficiency of 7,8-DHF in these tissues was also demonstrated by histopathological tests. SIGNIFICANCE: In conclusion, CAF diet-induced metabolic syndrome model, 7,8-DHF suppressed ERS and ERS-induced metabolic disorders in both liver and pancreas. Therefore, 7,8-DHF may potentially be a novel therapeutic compound to ameliorate ERS and related metabolic symptoms.
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Estrés del Retículo Endoplásmico , Síndrome Metabólico , Animales , Apoptosis , Dieta Alta en Grasa/efectos adversos , Flavonas , Masculino , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/etiología , Ratones , Ratones Endogámicos C57BLRESUMEN
AIM: To determine the effects of valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), topiramate (TPM), lamotrigine (LTG), and levetiracetam (LEV) on ovarian folliculogenesis in young rats. METHODS: Forty-nine female Wistar rats, aged 21-24 days, were divided equally into 7 experimental groups. These were given tap water over 21-24 days (control group), 300 mg/kg of VPA, 150 mg/kg of CBZ, 150 mg/kg of OXC, 100 mg/kg of TPM, 10 mg/kg of LTG, or 50 mg/kg of LEV daily in 2 doses via oral gavage until the end of puberty. At the end of the study, the estrous cycle of each rat was monitored daily, and those rats in pro-estrus or di-estrus were sacrificed and the ovaries removed. Serial sections obtained from the ovaries were stained with hematoxylin and eosin, and the corpora lutea and follicles were enumerated. Apoptotic cells were detected using the TUNEL technique. Various serial sections were immunohistochemically stained with proliferating cell nuclear antigen (PCNA), growth differentiation factor (GDF)-9, caspase-3, caspase-9, transforming growth factor beta 1 (TGF-1), and epidermal growth factor (EGF), and evaluated and photographed under a light microscope. KEY FINDINGS: The number of corpora lutea was significantly increased in the VPA, CBZ, OXC, and LTG groups compared to the control group (p < 0.001). The number of TUNEL-positive ovarian follicles was 3.3 ± 1.1 (median, 3), 6.1 ± 0.9 (median, 6), and 5.7 ± 0.8 (median,6) in the control, OXC and LEV groups, respectively (p < 0.001). The number of TUNEL-positive granulosa cells was higher in all the groups treated with antiepileptics, with the exception of the TPM group, compared to the control group (p < 0.001). HSCOREs for immunohistochemical staining using PCNA, GDF-9, TGF-1 and EGF were significantly higher in the control group than in the others (p < 0.001). HSCORE for staining using caspase-3 was significantly higher in the VPA, CBZ, OXC and LEV groups, while the HSCORE was significantly lower in the TPM group than in the control group. HSCORE for staining using caspase-9 was significantly higher in the VPA, CBZ and OXC groups, while it was significantly lower in the TPM group than in the control group (p < 0.001). SIGNIFICANCE: Exposure to VPA, CBZ, OXC, TPM, LTG and LEV caused different levels of impaired folliculogenesis in young rats.
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Anticonvulsivantes , Ácido Valproico , Animales , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Benzodiazepinas/farmacología , Carbamazepina/farmacología , Carbamazepina/uso terapéutico , Caspasa 3 , Caspasa 9/farmacología , Factor de Crecimiento Epidérmico/farmacología , Femenino , Lamotrigina/farmacología , Levetiracetam/farmacología , Ovario , Oxcarbazepina , Antígeno Nuclear de Célula en Proliferación/farmacología , Ratas , Ratas Wistar , Topiramato/farmacología , Ácido Valproico/farmacología , Ácido Valproico/uso terapéuticoRESUMEN
PURPOSE: The role of BDNF in adipose tissue metabolism is poorly understood. We investigated the effects of decreased levels of BDNF on the expression of major adipokines in different fat depots (e.g., subcutaneous and epididymal) of mouse groups fed three different diet protocols. METHODS: BDNF heterozygous (+ / -) mice were used to evaluate the effect of reduced BDNF levels. Six groups of C57BL/6 J breed wild type (WT) and BDNF (+ / -) mice were formed. These groups were fed, respectively, a control diet (CD), a high-fat diet (HFD), and a high-sucrose diet (HSD) for 4 months. Serum samples and adipose tissues were used for biochemical assays. The serum concentrations and tissue expression levels of leptin, adiponectin, and resistin were measured. RESULTS: Compared to the CD-fed WT group (control group), serum leptin and leptin expression levels were found to be higher in all experimental groups. Serum adiponectin levels were lower in the BDNF (+ / -) groups and HFD-fed WT group than in the control group. Epididymal adiponectin expression was found to be lower in the HFD-fed BDNF (+ / -) group and higher in HSD-fed groups than in the control group. Compared to the control group, adiponectin expression increased in the WT groups in subcutaneous adipose tissue. Serum resistin levels were elevated in the HFD-fed groups. Resistin expression in epididymal adipose tissue was lower in the CD-fed and HFD-fed groups than in the control group. CONCLUSIONS: BDNF levels and diet differentially affect the expression of adipokines in different fat tissues in the body. BDNF may play a protective role in obesity and diabetes.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Diabetes Mellitus , Leptina , Adipoquinas/metabolismo , Adiponectina , Tejido Adiposo/metabolismo , Animales , Diabetes Mellitus/metabolismo , Dieta Alta en Grasa , Humanos , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , ResistinaRESUMEN
INTRODUCTION: Obesity is known to cause sexual dysfunction including erectile dysfunction and poor semen quality. Lifestyle modifications such as exercise have increasingly been more recognized to lower the likelihood of having sexual dysfunction or infertility in obese men. In this context, as an exercise-mimetic hormone, irisin has a potential to improve obesity-related reproductive dysfunctions. We aimed to elucidate possible effects of irisin on high-fat diet (HFD)-induced reproductive dysfunction in obese male rats. METHODS: Rats were divided into four groups: vehicle, irisin, obese, and obese + irisin. The rats in obese and obese+irisin groups were fed with HFD (60% kcal fat) pellets for 12 weeks to induce obesity, and then obesity-induced sexual dysfunction was confirmed by the sexual behavior test (SBT). Irisin and obese+irisin groups received irisin (100 ng/kg/day) infusion by an s.c. osmotic minipump for 4 weeks after HFD-induced obesity was formed. RESULTS: Irisin did improve a number of measures of copulation, including penile erection, ejaculation, and sexual performance, and also improved sperm morphology and motility and decreased fat-induced testicular damage. It decreased serum leptin levels. On the other hand, irisin did not affect serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. It also increased gene expression of tyrosine hydroxylase (TH) and adrenoceptor alpha 1A (ADRA1A) in the medial preoptic area (mPOA) and nucleus accumbens (NAc). CONCLUSION: Irisin provided a marked enhancement of HFD-induced decrease in libido, potency, sexual performance, and erection in SBT. Taken together, our results emphasize that irisin has a restorative and improver role in HFD-induced reproductive dysfunctions in obese male rats.
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Dieta Alta en Grasa , Fibronectinas , Masculino , Ratas , Animales , Dieta Alta en Grasa/efectos adversos , Fibronectinas/metabolismo , Fibronectinas/farmacología , Leptina , Análisis de Semen/efectos adversos , Tirosina 3-Monooxigenasa , Semen/metabolismo , Obesidad/metabolismo , Hormona Luteinizante , Testosterona , Hormona Folículo Estimulante , Receptores AdrenérgicosRESUMEN
Sexual dysfunction is a common clinical condition due to different causes including the use of selective serotonin reuptake inhibitors (SSRI). Especially, SSRI paroxetine is known to cause numerous types of sexual dysfunction in men. There is growing interest in exercise as a non-pharmacological approach for the treatment of SSRI-induced sexual dysfunction. With these in mind, we investigated the effects of irisin, which is a recently detected exercise-linked hormone, on paroxetine-induced sexual dysfunction in male rats. Our findings showed that circulating irisin levels were lower in paroxetine-induced sexual dysfunction in male rats (20 mg/kg/day for 8 weeks by oral gavage than in vehicle-treated rats). In addition, results from sexual behavioral tests revealed that subcutaneous irisin perfusion (100 ng/kg/day via mini-osmotic pumps for 28 days) ameliorated sexual motivation and copulatory performance in sexually impaired male rats treated with paroxetine. The significantly reduced serum testosterone levels and α1-adrenoceptors (ADRA1A) and tyrosine hydroxylase gene (TH) expression levels in the nucleus accumbens (NAc) in paroxetine-induced sexually dysfunctioning male rats were markedly increased following irisin exposure. Similarly, the expression levels of ADRA1A and TH in the medial preoptic area (mPOA) significantly increased in male rats co-administered with paroxetine and irisin compared to the vehicle-treated male rats. These results demonstrate that irisin may be a therapeutic modality that mimics/supports the beneficial effects of exercise for improving SSRI-associated sexual dysfunction in men through increase in serum testosterone levels and increased expression of α1-adrenoceptors and TH in the NAc and mPOA associated with sexual motivation and copulatory behaviors.
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Paroxetina , Disfunciones Sexuales Fisiológicas , Animales , Humanos , Masculino , Paroxetina/farmacología , Ratas , Receptores Adrenérgicos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Conducta Sexual Animal , Disfunciones Sexuales Fisiológicas/inducido químicamente , Disfunciones Sexuales Fisiológicas/tratamiento farmacológico , Testosterona/farmacologíaRESUMEN
BACKGROUND: Breath-holding spells (BHS) are common non-paroxysmal events with unknown pathophysiology. BHS have been associated not only with iron deficiency anemia (IDA) but also with oxidant/antioxidant imbalance and erythrocyte injury induced by hypoxia. The present study was designed to investigate the contribution of IDA in BHS and the oxidant/antioxidant balance in children with or without IDA in BHS and compare them with healthy controls.Additionally, the study also aimed to examine the effect of the frequency of BHS attacks (mild or severe) on the oxidant/antioxidant balance and to determine the best predictive oxidant and antioxidant markers. MATERIALS AND METHODS: The study included 66 children with BHS aged 6-48 months who had been followed up for a minimum period of one year between 2014 and 2018. A control group of 30 age- and gender-matched healthy children was included in the study. The patient group was divided into 2 groups (IDA and non-IDA) and these groups were compared between each other and also with the control group. The IDA group was divided into subgroups based on the frequency of BHS attacks. Blood samples were obtained within a maximum period of 24 h following the spell. Levels of protein carbonyl, nitrite, nitrate, TOS, TAS, OSI, MDA, enzyme activities of GPx, CAT,enzyme activities of erythrocyte SOD, CAT, and GPx, and the level of MDA were measured. RESULTS: In patients with IDA, the oxidant levels increased while the antioxidant enzyme activities decreased. In all patients, the levels of MDA, carbonyl, TOS, OSI increased and the levels of TAS, activities SOD, and CAT decreased, whereas the enzyme activities of erythrocyte SOD, CAT, GPx decreased significantly compared to those of control group. Increased of erythrocyte MDA levels had 10.32, decreased enzyme activities of erythrocyte SOD levels had a 10.25, and decreased enzyme activities of erythrocyte CAT had a 5.33 times greater risk for spell. CONCLUSION: The results indicated that the oxidant/antioxidant balance in children with BHS was impaired in favor of oxidants at both levels, regardless of the presence of IDA and the increased frequency of BHS attacks per day. Moreover, the presence of IDA was found to be associated with increased oxidative stress in children with BHS, particularly at the erythrocyte level. Erythrocyte level; among the erythrocyte MDA oxidant parameters, erythrocyte SOD and antioxidant parameters, they are the biomarkers that show the best probability of having a BHS attack and an increase in the frequency of apnea attacks.
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Anemia Ferropénica , Estrés Oxidativo , Anemia Ferropénica/diagnóstico , Antioxidantes , Biomarcadores , Niño , Eritrocitos , HumanosRESUMEN
We investigated the effects of increased intra-abdominal pressure during laparoscopy on the endocrine and exocrine functions, oxidative stress and histopathology of the pancreas in rats. We established three experimental groups of eight animals. Group 1 was the untreated control. Forth other two groups, pneumoperitoneum with CO2 was established for 60 min at 6 mm Hg for group 2 and 12 mm Hg for group 3; groups 2 and 3 animals were allowed to re-perfuse for 30 min. Amylase, glucagon and insulin levels were analyzed in blood samples and insulin:glucagon ratio was calculated. Histopathology and malondialdehyde assay were performed on pancreatic tissue samples. Histological damage scores for vasocongestion were increased significantly in groups 2 and 3 compared to group 1. Histological damage scores for inflammatory cell infiltration were increased significantly in group 3 compared to group 1. Malondialdehyde levels were increased significantly in group 3 compared to group 1. We found no significant differences among groups for serum amylase levels or histological damage scores for hemorrhage. Insulin and glucagon levels, and the insulin:glucagon ratio was increased significantly in group 3 compared to groups 1 and 2. We found that in rats routine laparoscopy caused increased serum insulin and glucagon levels, and histopathological changes that indicated ischemia-reperfusion injury to the pancreas.
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Estrés Oxidativo , Neumoperitoneo , Animales , Dióxido de Carbono , Páncreas , Neumoperitoneo Artificial , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: We aimed to evaluate the protective effect of edaravone on radiation-induced ovarian damage in an experimental rat model. METHODS: Thirty-two Wistar albino female rats were randomly divided into four groups. Group 1: control, no treatment, and radiation was applied throughout the study; Group 2: sham, only radiation was applied; Group 3: 45 mg/kg edaravone and radiation were applied; Group 4: 450 mg/kg edaravone and radiation were applied. Edaravone was administered intraperitoneally 30 min before radiotherapy (5 Gy). Two days after radiation exposure, the rats were sacrificed and the ovaries were removed. Histologic changes under light microscopy and immunoreactivity for anti-caspase-3 were noted and compared between the four groups. RESULTS: There was a statistically significant difference in follicle counts, vascular congestion, edema, cytoplasmic vacuolization, hemorrhage, and interstitial cell degeneration between the groups. Radiation causes deterioration in most histopathological parameters. Administration of edaravone at different doses seems to reverse these alterations and alleviate the injury. Antioxidant defense mechanisms appear to be enhanced by edaravone as shown by histopathologically and decreased apoptosis by reducing the expression of anti-caspase-3 activity as demonstrated immunohistochemically. CONCLUSION: This is the first study evaluating the protective effects of edaravone on radiation-induced ovarian damage. Edaravone decreased the follicular apoptosis and attenuates the radiation-induced ovarian damage in rats.
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Edaravona/uso terapéutico , Depuradores de Radicales Libres/uso terapéutico , Ovario/efectos de la radiación , Traumatismos por Radiación/prevención & control , Daño por Reperfusión/prevención & control , Animales , Modelos Animales de Enfermedad , Edaravona/administración & dosificación , Femenino , Depuradores de Radicales Libres/administración & dosificación , Depuradores de Radicales Libres/farmacología , Ovario/patología , Ratas , Ratas Wistar , Daño por Reperfusión/patologíaRESUMEN
The purpose of this study was to investigate the effect of homocysteine (Hcy) on CD36, PPARγ, and C/EBPα gene and protein expression in adipose tissue obtained from normal and high-calorie diet obesity models. CD36, PPARγ, and C/EBPα gene expression and protein levels in adipose tissue specimens were determined using the RT-PCR and ELISA methods, respectively. Significantly increased CD36 gene expression was observed in adipose tissue from obese mice, while Hcy significantly reduced CD36 gene expression in adipose tissue from normal and obese mice. PPARγ and C/EBPα gene expression levels decreased significantly in all groups compared to the normal group. In addition, levels of both PPARγ and C/EBPα gene expression were lower with Hcy supplementation compared to their own controls. In conclusion, Hcy's reduction of CD36 gene expression in adipose tissue may be one probable factor in hyperhomocysteinemia representing an independent risk factor for cardiovascular diseases.