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1.
Mol Biol Rep ; 51(1): 1046, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39388029

RESUMEN

BACKGROUND: Exosomes (Exos) are candidates for functional recovery and regeneration following sciatic nerve crushed (SNC) injury due to their composition which can accelerate tissue regeneration. Therefore, mouse embryonic fibroblast-derived exosomes were evaluated for their regenerative capacity in SNC injury. METHODS AND RESULTS: In the study, 40 Balb/c males (20 ± 5 g) and two pregnant mice (for embryonic fibroblast tissue) were used and crushed injury was induced in the left sciatic nerve with an aneurysm clamp. Sciatic nerve model mice were randomly divided into 5 groups (n = 8; control, n = 8; sham, n = 8; SNC, n = 8; Mouse embryonic fibroblast exosome (mExo), n = 8; SNC + Mouse embryonic fibroblast exosome (SNC + mExo). Rotarod tests for motor functions and hot plate and von Frey tests for sensory functions were analyzed in the groups. Expression changes of exosome genes (RARRES1, NAGS, HOXA13, and MEIS1) immunohistochemical analysis of these gene proteins, and structural exosome NF-200 and S100 proteins were evaluated by confocal microscopy. Behavioral analyses showed that the damage in SNC was significant between groups on day14 and day28 (P < 0.05). In behavioral analyses, it was determined that motor functions and mechanical sensitivity lost in SNC were regained after mExo treatment. While expression of all genes was detected in MEF-derived exosomes, the high expression was MESI1 and the low expression was HOXA13. NF200, an indicator of axon number and neurofilament density, was found to decrease in SNC (P < 0.001) and increase after treatment, but not significantly. The decreased S100 protein levels in SNC and the increase detected after treatment were not significant. CONCLUSION: The expression of four mRNAs in mExos indicates that these genes may have an effect on regenerative processes after SNC injury. The regenerative process supported by tissue protein expressions demonstrates the therapeutic potential of mExo treatment.


Asunto(s)
Modelos Animales de Enfermedad , Exosomas , Fibroblastos , Regeneración Nerviosa , Nervio Ciático , Animales , Exosomas/metabolismo , Exosomas/genética , Ratones , Fibroblastos/metabolismo , Nervio Ciático/lesiones , Nervio Ciático/metabolismo , Masculino , Femenino , Ratones Endogámicos BALB C , Lesiones por Aplastamiento/genética , Lesiones por Aplastamiento/metabolismo , Compresión Nerviosa , Proteínas de Neurofilamentos/metabolismo , Proteínas de Neurofilamentos/genética
2.
Int J Neurosci ; 132(1): 23-30, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32677492

RESUMEN

INTRODUCTION: Antidepressants increase the level of 5-HT in the somatodendritic region of the serotonergic dorsal raphe nucleus (DRN) neurons in the first few days of their usage, which, in turn, inhibits the serotonergic neurons locally. Pindolol may eliminate this inhibition when used in combination with antidepressants. MATERIAL AND METHODS: We aimed to determine the effect of pindolol on 5-HT1A receptor response in the DRN neurons, using voltage clamp recordings and prove the potentiation of antidepressant effect of venlafaxine by pindolol through behavior experiments. Balb/c mice, 28-35 days-old were used. RESULTS: 5-HT application (25 µM) induced an outward current by 23.36 ± 3.79 pA at the neurons in the dorsal subnucleus of DRN. This effect was inhibited by pre-administration of WAY-100135 (21 µM) and pindolol (10 µM) separately. The current induced by 5-HT and 8-OHDPAT have no statistically significance. 8-OHDPAT (30 µM) induced a 5-HT-like outward current, which was inhibited by pre-administration of pindolol (10 µM). Combination of venlafaxine (20 mg/kg/day) and pindolol (15 mg/kg/day) significantly reduced immobilization time when compared to the control group in tail suspension test and forced swim test without any significant change in locomotor activity. Administration of venlafaxine (20 mg/kg/day) alone or pindolol (15 mg/kg/day) alone did not significantly reduce immobilization time. CONCLUSION: Pindolol has the potential to prevent the inhibition of serotonergic neurons after antidepressant use. Hence, we, for the first time, demonstrated that pindolol can potentiate antidepressant effect of venlafaxine. In the mood disorders, pindolol is likely to increase the effectiveness of antidepressant drugs when given in combination.


Asunto(s)
Antidepresivos/farmacología , Núcleo Dorsal del Rafe/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Pindolol/farmacología , Receptor de Serotonina 5-HT1A/efectos de los fármacos , Antagonistas de la Serotonina/farmacología , Clorhidrato de Venlafaxina/farmacología , Animales , Antidepresivos/administración & dosificación , Conducta Animal/efectos de los fármacos , Sinergismo Farmacológico , Ratones , Ratones Endogámicos BALB C , Pindolol/administración & dosificación , Piperazinas/farmacología , Antagonistas de la Serotonina/administración & dosificación , Clorhidrato de Venlafaxina/administración & dosificación
3.
Artículo en Inglés | MEDLINE | ID: mdl-31451914

RESUMEN

Acid-sensing ion channels (ASICs) are voltage-independent and proton-gated channels. In this study, we aimed to test the hypothesis whether ASICs might be involved in modifying the excitability of stellate cells in the cochlear nucleus (CN). We determined gene expressions of ASIC1, ASIC2 and ASIC3 in the CN of BALB/mice. ASIC currents in stellate cells were characterized by using whole-cell patch-clamp technique. In the voltage-clamp experiments, inward currents were recorded upon application of 2-[N-Morpholino ethanesulfonic acid]-normal artificial cerebrospinal fluid (MES-aCSF), whose pH 50 was 5.84. Amiloride inhibited the acid-induced currents in a dose-dependent manner. Inhibition of the ASIC currents by extracellular Ca2+ and Pb2+ (10 µM) was significant evidence for the existence of homomeric ASIC1a subunits. ASIC currents were increased by 20% upon extracellular application of Zn2+ (300 µM) (p < 0.05, n = 13). In current-clamp experiments, application of MES-aCSF resulted in the depolarization of stellate cells. The results show that the ASIC currents in stellate cells of the cochlear nucleus are carried largely by the ASIC1a and ASIC2a channels. ASIC channels affect the excitability of the stellate cells and therefore they appear to have a role in the processing of auditory information.


Asunto(s)
Canales Iónicos Sensibles al Ácido/metabolismo , Percepción Auditiva/fisiología , Núcleo Coclear/fisiología , Neuronas/fisiología , Animales , Ratones , Ratones Endogámicos BALB C
4.
An Acad Bras Cienc ; 91(2): e20180547, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31038539

RESUMEN

Dynamic thiol-disulfide homeostasis is considered to have critical roles in maintenance of physiological functioning. We aimed to reveal whether there is any specific aberration in thiol-disulfide homeostasis in three distinct categories of individuals, including those who 1) exercise regularly (fitness group), 2) have a sedentary lifestyle (sedentary group) and 3) are overweight or obese (overweight/obese group). 72 male individuals were included in the study, 21 of whom were in fitness group, 28 of whom were overweight or obese and 23 of whom had a sedentary lifestyle. Plasma native thiol (-SH) and total thiol [(-SH) + (-S-S-)] levels were quantitatively determined. Total thiol levels in sedentary group were significantly lower than those in overweight/obese (p<0.05) and fitness groups (p<0.001). Also, disulfide values in fitness group were significantly higher than those in sedentary and overweight/obese groups (p<0.005, p<0.05). On the other hand, disulfide level, reduced and oxidized thiol ratios and oxidation/reduction ratio in fitness group differed significantly from the other groups (p<0.05). Thiol-disulfide homeostasis varies depending on lifestyle. The results of our study indicate that higher total thiol and disulfide levels are conspicuously distinctive features of thiol-disulfide homeostasis in individuals exercising regularly.


Asunto(s)
Disulfuros/sangre , Ejercicio Físico/fisiología , Obesidad/sangre , Sobrepeso/sangre , Conducta Sedentaria , Compuestos de Sulfhidrilo/sangre , Adulto , Análisis de Varianza , Antioxidantes/fisiología , Índice de Masa Corporal , Homeostasis/fisiología , Humanos , Masculino , Estrés Oxidativo/fisiología , Curva ROC , Valores de Referencia , Estadísticas no Paramétricas
5.
J Membr Biol ; 251(5-6): 711-722, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30206647

RESUMEN

ERG (ether-a-go-go-related gene) channels are the members of the voltage-dependent potassium channel family, which have three subtypes, as ERG1 (Kv 11.1), ERG2 (Kv 11.2), and ERG3 (Kv11.3). There is no information on ERG channels in the cochlear nucleus (CN) neurons, which is the first relay station of the auditory pathway. As occur in some of congenital long QT Syndromes (LQTS), mutation of the KCNQ11 genes for ERG channel has been reported to be accompanied by hearing loss. For that reason, we aimed to study biophysical properties and physiological importance, and contribution of ERG K+ currents to the formation of action potentials in the stellate and bushy neurons of the ventral cochlear nucleus (VCN). A total of 70 mice at 14-17 days old were used for this study. Electrophysiological characterization of ERG channels was performed using patch-clamp technique in the CN slices. In current clamp, ERG channel blockers, terfenadine (10 µM) and E-4031 (10 µM), were applied in both cell types. The activation, inactivation, and deactivation kinetics of the ERG channels were determined by voltage clamp. In conclusion, the findings obtained in the present study suggest that stellate and bushy neurons express ERG channels and ERG channels appear to contribute to setting action potential (AP) frequency, threshold for AP induction, and, possibly, resting membrane potentials in this cells.


Asunto(s)
Núcleo Coclear/metabolismo , Canales de Potasio Éter-A-Go-Go/metabolismo , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Vías Auditivas/efectos de los fármacos , Vías Auditivas/fisiología , Núcleo Coclear/efectos de los fármacos , Electrofisiología , Canales de Potasio Éter-A-Go-Go/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Ratones , Piperidinas/farmacología , Piridinas/farmacología , Ganglio Estrellado/efectos de los fármacos , Ganglio Estrellado/metabolismo , Terfenadina/farmacología
6.
J Membr Biol ; 251(1): 163-178, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29379989

RESUMEN

Major voltage-activated ionic channels of stellate cells in the ventral part of cochlear nucleus (CN) were largely characterized previously. However, it is not known if these cells are equipped with other ion channels apart from the voltage-sensitive ones. In the current study, it was aimed to study subunit composition and function of ATP-sensitive potassium channels (KATP) in stellate cells of the ventral cochlear nucleus. Subunits of KATP channels, Kir6.1, Kir6.2, SUR1, and SUR2, were expressed at the mRNA level and at the protein level in the mouse VCN tissue. The specific and clearly visible bands for all subunits but that for Kir6.1 were seen in Western blot. Using immunohistochemical staining technique, stellate cells were strongly labeled with SUR1 and Kir6.2 antibodies and moderately labeled with SUR2 antibody, whereas the labeling signals for Kir6.1 were too weak. In patch clamp recordings, KATP agonists including cromakalim (50 µM), diazoxide (0.2 mM), 3-Amino-1,2,4-triazole (ATZ) (1 mM), 2,2-Dithiobis (5-nitro pyridine) (DTNP) (330 µM), 6-Chloro-3-isopropylamino- 4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NNC 55-0118) (1 µM), 6-chloro-3-(methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NN414) (1 µM), and H2O2 (0.88 mM) induced marked responses in stellate cells, characterized by membrane hyperpolarization which were blocked by KATP antagonists. Blockers of KATP channels, glibenclamide (0.2 mM), tolbutamide (0.1 mM) as well as 5-hydroxydecanoic acid (1 mM), and catalase (500 IU/ml) caused depolarization of stellate cells, increasing spontaneous action potential firing. In conclusion, KATP channels seemed to be composed dominantly of Kir 6.2 subunit and SUR1 and SUR2 and activation or inhibition of KATP channels regulates firing properties of stellate cells by means of influencing resting membrane potential and input resistance.


Asunto(s)
Núcleo Coclear/efectos de los fármacos , Núcleo Coclear/metabolismo , Canales de Potasio de Rectificación Interna/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Óxidos S-Cíclicos/farmacología , Diazóxido/análogos & derivados , Diazóxido/farmacología , Peróxido de Hidrógeno , Canales KATP/agonistas , Canales KATP/antagonistas & inhibidores , Canales KATP/metabolismo , Ratones , Ratones Endogámicos BALB C , Canales de Potasio de Rectificación Interna/agonistas , Canales de Potasio de Rectificación Interna/antagonistas & inhibidores , Tolbutamida/farmacología
7.
Arch Gynecol Obstet ; 296(5): 941-946, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28866782

RESUMEN

OBJECTIVE: To investigate the effect of adnexal torsion on the plasma heat shock protein 70 level and to determine whether plasma heat shock protein 70 can be used in the adnexal torsion diagnosis. MATERIALS AND METHODS: Twenty-one nulligravid 3-month-old female Wistar albino rats were randomly and equally allocated into three groups: study group (ovarian torsion) (n = 7), laparotomy group (sham operation) (n = 7) and control group (received no special treatment) (n = 7). Ovarian torsion model was created by twisting the right adnexa two times around its pedicle and fixing over the lateral pelvis with 6.0 polyglactin absorbable surgical suture. Blood was sampled before and 12 h after operation to assess plasma heat shock protein 70 level. RESULTS: In the study group, the mean plasma heat shock protein 70 level was significantly higher than that in the laparotomy and control groups (1.75 ± 0.25), (1.16 ± 0.99), (1.19 ± 0.11) ng/ml, respectively, P = 0.001), following 12 h of ovarian torsion. CONCLUSION: A significant increase in plasma heat shock protein 70 level in the study group indicates that plasma heat shock protein 70 level could be used as a serum marker in the early detection of adnexal torsion. However, further clinical and experimental studies of a larger size are required.


Asunto(s)
Anexos Uterinos/irrigación sanguínea , Proteínas HSP70 de Choque Térmico/sangre , Anomalía Torsional/diagnóstico , Animales , Biomarcadores/sangre , Femenino , Humanos , Ratas , Ratas Wistar , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Anomalía Torsional/sangre , Anomalía Torsional/patología
8.
Int J Exp Pathol ; 96(5): 332-7, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26568164

RESUMEN

The potential toxic effects of several pesticides, including imidacloprid on non-target organisms have not been clearly established. Also, the chronic effects of non-toxic doses on cognitive function in mammals are unknown. In this study, the effects of different doses of imidacloprid on learning and memory of infant and adult rats were evaluated, and the expressions of genes synthesizing proteins known to be associated with learning in brain tissues were also documented. 0.5, 2 and 8 mg/kg doses of imidacloprid were administered to newborn infant and adult Wistar albino rats by gavage. Their learning activities were evaluated, and the expression levels of the inotropic glutamate receptor GRIN1, synoptophysin, growth-associated protein 43 and the muscarinic receptor M1 in hippocampus were determined by real-time PCR method. Learning activities were diminished significantly at 2 and 8 mg/kg doses in the infant model groups and at 8 mg/kg dose in adult rats. Also, expression levels of GRIN1, SYP and GAP-43 were found to be insignificantly altered. Only the expression of M1 were significantly changed in high doses of adult group. Thus imidacloprid in high doses causes deterioration in cognitive functions particularly in infant rats, and this deterioration may be associated with changes in the expressions of related genes.


Asunto(s)
Cognición/efectos de los fármacos , Imidazoles/toxicidad , Insecticidas/toxicidad , Aprendizaje/efectos de los fármacos , Nitrocompuestos/toxicidad , Transcriptoma/efectos de los fármacos , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Masculino , Neonicotinoides , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa
9.
J Recept Signal Transduct Res ; 34(4): 317-24, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24646197

RESUMEN

BACKGROUND: Hyperhomocysteinemia (HHcy) is associated with neurodegenerative diseases. Transient receptor potential melastatin (TRPM2) and TRPM7 channels may be activated by oxidative stress. Hydrated C(60) fullerene (C(60)HyFn) have recently gained considerable attention as promising candidates for neurodegenerative states. We aimed to examine the effects on TRPM2 and TRPM7 gene expression of C(60)HyFn due to marked antioxidant activity in HHcy mice. METHODS: C57BL/6 J. mice were divided into four groups: (1) Control group, (2) HHcy, (3) HHcy + C(60)HyFn-treated group and (4) C(60)HyFn-treated group. TRPM2 and TRPM7 gene expression in brains of mice were detected by real-time PCR, Western blotting and immunohistochemistry. Apoptosis in brain were assessed by TUNEL staining. RESULTS: mRNA expression levels of TRPM2 were significantly increased in HHcy group compared to the control group. C(60)HyFn administration significantly decreased serum levels of homocysteine and TRPM2 mRNA levels in HHcy + C(60)HyFn group. Whereas, HHcy-treatment and C(60)HyFn administration did not change the expression of TRPM7. CONCLUSION: Administration of C(60)HyFn in HHcy mice significantly reduces serum homocysteine level, neuronal apoptosis and expression level of TRPM2 gene. Increased expression level of TRPM2 induced by oxidative stress might be involved in the ethiopathogenesis of HHcy related neurologic diseases.


Asunto(s)
Fulerenos/administración & dosificación , Hiperhomocisteinemia/tratamiento farmacológico , Canales Catiónicos TRPM/biosíntesis , Animales , Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hiperhomocisteinemia/genética , Ratones , Estrés Oxidativo/efectos de los fármacos , ARN Mensajero/biosíntesis
10.
J Neurosci ; 32(27): 9301-11, 2012 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-22764237

RESUMEN

Broadband transient sounds, such as clicks and consonants, activate a traveling wave in the cochlea. This wave evokes firing in auditory nerve fibers that are tuned to high frequencies several milliseconds earlier than in fibers tuned to low frequencies. Despite this substantial traveling wave delay, octopus cells in the brainstem receive broadband input and respond to clicks with submillisecond temporal precision. The dendrites of octopus cells lie perpendicular to the tonotopically organized array of auditory nerve fibers, placing the earliest arriving inputs most distally and the latest arriving closest to the soma. Here, we test the hypothesis that the topographic arrangement of synaptic inputs on dendrites of octopus cells allows octopus cells to compensate the traveling wave delay. We show that in mice the full cochlear traveling wave delay is 1.6 ms. Because the dendrites of each octopus cell spread across approximately one-third of the tonotopic axis, a click evokes a soma-directed sweep of synaptic input lasting 0.5 ms in individual octopus cells. Morphologically and biophysically realistic, computational models of octopus cells show that soma-directed sweeps with durations matching in vivo measurements result in the largest and sharpest somatic EPSPs. A low input resistance and activation of a low-voltage-activated potassium conductance that are characteristic of octopus cells are important determinants of sweep sensitivity. We conclude that octopus cells have dendritic morphologies and biophysics tailored to accomplish the precise encoding of broadband transient sounds.


Asunto(s)
Ondas Encefálicas/fisiología , Nervio Coclear/citología , Nervio Coclear/fisiología , Núcleo Coclear/citología , Núcleo Coclear/fisiología , Dendritas/fisiología , Modelos Neurológicos , Estimulación Acústica/métodos , Animales , Vías Auditivas/citología , Vías Auditivas/fisiología , Cóclea/inervación , Cóclea/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos CBA , Ratones Endogámicos ICR
11.
Drug Chem Toxicol ; 36(4): 421-9, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23527526

RESUMEN

Clothianidin (CTD) is a novel, broad-spectrum insecticide. In the current study, it was aimed to study the effect of subchronic exposure to low doses of CTD (2, 8 and 24 mg/kg body weight/day) on the reproductive system in adult rats. CTD treatment did not significantly change serum testosterone level or sperm parameters (e.g. concentration, motility and morphology), but caused significant decreases in weights of epididymis, right cauda epididymis and seminal vesicles. CTD treatment did not cause sperm DNA fragmentation and did not change the apoptotic index in the seminiferous tubules and levels of α-tocopherol and glutathione, but increased the level of thiobarbituric acid-reactive substances and cholesterol levels significantly at all doses. CTD exposure caused significant elevations in palmitic, linoleic and arachidonic acids in testis in all CTD-exposed groups. There was a drop in 20:4/18:2 (arachidonic acid/linoleic acid) ratio and an increase in 18:1n-9/18:0 (oleic acid/stearic acid) ratios in all CTD groups, in comparison to the control group. In conclusion, CTD had little detectable detrimental effects on the reproductive system of male rats over the measured parameters.


Asunto(s)
Genitales Masculinos/efectos de los fármacos , Guanidinas/toxicidad , Insecticidas/toxicidad , Tiazoles/toxicidad , Análisis de Varianza , Animales , Colesterol/metabolismo , Fragmentación del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Epidídimo/efectos de los fármacos , Glutatión/metabolismo , Masculino , Neonicotinoides , Ratas , Vesículas Seminales/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Testosterona/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Pruebas de Toxicidad , alfa-Tocoferol/metabolismo
12.
Cell Biol Toxicol ; 28(3): 187-200, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22431174

RESUMEN

Clothianidin (CTD) is one of the latest members of the synthetic organic insecticides, the neonicotinoids. In the present study, it was aimed to investigate if daily oral administration of CTD at low doses for 90 days has any deleterious effects on reproductive functions of developing male rats. Animals were randomly divided into four groups of six rats each, assigned as control rats, or rats treated with 2 (CTD-2), 8 (CTD-8) or 32 (CTD-32) mg CTD/kg body weight by oral gavage. The significant decreases of the absolute weights of right cauda epididymis and seminal vesicles, and body weight were detected in the animals exposed to CTD administration at 32 mg/kgBW/day. Epididymal sperm concentration decreased significantly in CTD-32 group and the abnormal sperm rates increased in CTD-8 and CTD-32 groups when compared to control group. The testosterone level was significantly decreased in CTD-32 group when compared to control group. The administration of all CTD doses resulted in a significant decrease in the level of GSH. The number of TUNEL-positive cells significantly increased in the germinal epithelium of testis of rats exposed to CTD at 32 mg/kgBW/day. In groups CTD-8 and CTD-32, only docosapentaenoic, arachidonic, palmitic and palmitoleic acids were significantly elevated when compared to control. The ratios of 20:4/18:2 and 18:1n-9/18:0 were decreased when rats exposed to CTD. Sperm DNA fragmentation was observed in CTD-32 group, but not CTD-2 and CTD-8. It is concluded that low doses of CTD exposure during critical stages of sexual maturation had moderate detrimental effects on reproductive organ system and more severe effects are likely to be observed at higher dose levels. In addition, the reproductive system may be more sensitive to exposure of CTD even earlier in development (prenatal and early postnatal), and therefore it could be expected that more severe effects could also be observed at the NOAEL dose levels, if dosing had occurred in utero or early postnatal.


Asunto(s)
Apoptosis , Epidídimo/efectos de los fármacos , Guanidinas/efectos adversos , Espermatozoides/efectos de los fármacos , Tiazoles/efectos adversos , Animales , Ácido Araquidónico/metabolismo , Fragmentación del ADN , Epidídimo/crecimiento & desarrollo , Epidídimo/patología , Ácidos Grasos Insaturados/metabolismo , Glutatión/metabolismo , Guanidinas/administración & dosificación , Etiquetado Corte-Fin in Situ , Insecticidas/efectos adversos , Masculino , Neonicotinoides , Tamaño de los Órganos , Ácido Palmítico/metabolismo , Ratas , Ratas Wistar , Espermatozoides/metabolismo , Espermatozoides/patología , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , Testosterona/metabolismo , Tiazoles/administración & dosificación , Pruebas de Toxicidad Subcrónica/métodos
13.
Cell Biochem Funct ; 30(6): 492-9, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22522919

RESUMEN

We investigated whether treatment with imidacloprid would induce morphological changes, DNA fragmentation, antioxidant imbalance and apoptosis in the reproductive system of developing male rats. Twenty-four male rats were included in this 90-day study, starting at 7 days of age. The rats were divided into four groups. The first group was used as control. The second, third and fourth groups received oral 0.5-, 2- and 8-mg/kg imidacloprid, respectively. Serum, sperm and testis samples were collected from all groups at the end of the experimental period. The weights of the epididymis, vesicula seminalis, epididymal sperm concentration, body weight gain, testosterone and reduced glutathione values were lower in the imidacloprid-treated groups than that in the controls. All treated groups had increased lipid peroxidation, fatty acid concentrations and higher rates of abnormal sperm. Apoptosis and fragmentation of seminal DNA were higher in rats treated at the two higher doses of imidacloprid. These results show that this compound has a negative effect on sperm and testis of rats.


Asunto(s)
Daño del ADN , Epidídimo/efectos de los fármacos , Epidídimo/metabolismo , Imidazoles/farmacología , Insecticidas/farmacología , Nitrocompuestos/farmacología , Testículo/efectos de los fármacos , Testículo/patología , Animales , Apoptosis/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Epidídimo/patología , Lípidos/análisis , Masculino , Neonicotinoides , Oxidación-Reducción , Ratas , Ratas Wistar , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Espermatozoides/patología , Testículo/metabolismo , Testosterona/sangre
14.
J Environ Sci Health B ; 47(5): 434-44, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22424069

RESUMEN

In the current study it was aimed to investigate the toxicity of low doses of imidacloprid (IMI) on the reproductive organ systems of adult male rats. The treatment groups received 0.5 (IMI-0.5), 2 (IMI-2) or 8 mg IMI/kg body weight by oral gavage (IMI-8) for three months. The deterioration in sperm motility in IMI-8 group and epidydimal sperm concentration in IMI-2 and IMI-8 groups and abnormality in sperm morphology in IMI-8 were significant. The levels of testosterone (T) and GSH decreased significantly in group IMI-8 compared to the control group. Upon treatment with IMI, apoptotic index increased significantly only in germ cells of the seminiferous tubules of IMI-8 group when compared to control. Fragmentation was striking in the seminal DNA from the IMI-8 group, but it was much less obvious in the IMI-2 one. IMI exposure resulted in elevation of all fatty acids analyzed, but the increases were significant only in stearic, oleic, linoleic and arachidonic acids. The ratios of 20:4/20:3 and 20:4/18:2 were decreased and 16:1n-9/16:0 ratio was increased. In conclusion, the present animal experiments revealed that the treatment with IMI at NOAEL dose-levels caused deterioration in sperm parameters, decreased T level, increased apoptosis of germ cells, seminal DNA fragmentation, the depletion of antioxidants and change in disturbance of fatty acid composition. All these changes indicate the suppression of testicular function.


Asunto(s)
Exposición a Riesgos Ambientales , Imidazoles/toxicidad , Nitrocompuestos/toxicidad , Plaguicidas/toxicidad , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Adulto , Animales , Fragmentación del ADN/efectos de los fármacos , Humanos , Masculino , Neonicotinoides , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Wistar , Motilidad Espermática/efectos de los fármacos , Espermatozoides/citología , Espermatozoides/metabolismo , Testículo/citología , Testículo/crecimiento & desarrollo , Testículo/metabolismo , Testosterona/metabolismo
15.
Brain Res Bull ; 170: 115-128, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33581312

RESUMEN

ATP-sensitive potassium (KATP) channels and transient receptor potential melastatin 2 (TRPM2) channels are commonly expressed both pre- and postsynaptically in the central nervous system (CNS). We hypothesized that KATP and TRPM2 may couple metabolic status to the resting membrane potential of octopus neurons of the mouse ventral cochlear nucleus (VCN). Therefore, we studied the expression of KATP channels and TRPM2 channels in octopus cells by immunohistochemical techniques and their contribution to neuronal electrical properties by the electrophysiological patch clamp technique. In immunohistochemical staining of octopus cells, labelling with Kir6.2 and SUR1 antibodies was strong, and labelling with the SUR2 antibody was moderate, but labelling with Kir6.1 was very weak. Octopus cells had intense staining with TRPM2 antibodies. In patch clamp recordings, bath application of KATP channel agonists H2O2 (880 µM), ATZ (1 mM), cromakalim (50 µM), diazoxide (200 µM), NNC 55-0118 and NN 414 separately resulted in hyperpolarizations of resting potential to different extents. Application of 8-Bro-cADPR (50 µM), a specific antagonist of TRPM2 channels, in the presence of H2O2 (880 µM) resulted in further hyperpolarization by approximately 1 mV. The amplitudes of H2O2-induced outward KATP currents and ADPR-induced inward currents were 206.1 ± 31.5 pA (n = 4) and 136.8 ± 22.4 pA, respectively, at rest. Their respective reversal potentials were -77 ± 2.6 mV (n = 3) and -6.3 ± 2.9 (n = 3) and -6.3 ± 2.9 (n = 3). In conclusion, octopus cells appear to possess both KATP channels and TRPM2-like channels. KATP might largely be constituted by SUR1-Kir6.2 subunits and SUR2-Kir6.2 subunits. Both KATP and TRPM2-like channels might have a modulatory action in setting the membrane potential.


Asunto(s)
Núcleo Coclear/metabolismo , Canales KATP/metabolismo , Neuronas/metabolismo , Canales Catiónicos TRPM/metabolismo , Animales , Metabolismo Energético/fisiología , Potenciales de la Membrana/fisiología , Ratones
16.
J Membr Biol ; 237(1): 51-8, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20871985

RESUMEN

We investigated the effects of acamprosate on alcohol-induced oxidative toxicity, microsomal membrane Ca(2+)-ATPase (MMCA) activity and N-methyl-D: -aspartate receptor (NMDAR) subunits in rat brain. Forty male rats were equally divided into four groups. The first group was used as control, and the second group received ethanol. Acamprosate and acamprosate plus ethanol each day were administered to rats constituting the third and fourth groups for 21 days, respectively. Brain cortical and hippocampal samples were taken from the four groups after 21 days. Brain cortical lipid peroxidation (LP) levels and MMCA activity were higher in the alcohol group than in control, although glutathione peroxidase (GSH-Px), vitamin C, vitamin E and ß-carotene values were lower in the alcohol group than in control. LP levels were further increased in the acamprosate and alcohol + acamprosate groups compared with the alcohol group. GSH-Px, vitamin A, vitamin C, vitamin E and ß-carotene in the acamprosate and alcohol + acamprosate groups were further decreased compared with the alcohol group. Hippocampal NMDAR 2A and 2B subunit concentrations were lower in the alcohol group than in control, although they were increased by acamprosate and alcohol + acamprosate. Brain cortical MMCA activity was higher in the acamprosate group than in the alcohol-treated rats, although its activity was lower in the alcohol + acamprosate group than in the acamprosate group. Brain cortical reduced glutathione levels were not found to be statistically different in any of the groups. Oxidative stress has been proposed to explain the biological side effects of experimental alcohol intake. Acamprosate and alcohol-induced oxidative stress decreased brain antioxidant vitamins in the alcoholic rats.


Asunto(s)
ATPasas Transportadoras de Calcio/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Microsomas/enzimología , Estrés Oxidativo/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Taurina/análogos & derivados , Acamprosato , Disuasivos de Alcohol/farmacología , Animales , Ácido Ascórbico/metabolismo , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Microsomas/efectos de los fármacos , Ratas , Ratas Wistar , Taurina/farmacología , Vitamina E/metabolismo , beta Caroteno/metabolismo
17.
Cell Biochem Funct ; 28(4): 300-5, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20517894

RESUMEN

Oxidative stress occurs during maximal exercise, perhaps as a result of increased consumption of oxygen. Vitamins C and E can overcome the effects of antioxidants in exercise. We investigated the effects of supplementation with a combination of vitamin C and E (VCE) on blood lipid peroxidation (LP) and antioxidant levels following maximal training in basketball players.Blood samples were taken from 14 players (group A) and divided into two subgroups namely maximal training (group B) and maximal training plus VCE groups (group C). Group B maximally exercised for 35 days. VCE was supplemented to group C for 35 days and blood samples were taken from group B and C. Plasma and hemolyzed erythrocyte samples were obtained from the players.Erythrocyte glutathione peroxidase (GSH-Px) activity and plasma vitamin E concentration were lower in group B than in group A, whereas plasma and erythrocyte LP levels were higher in group B than in group A. Plasma vitamin A, vitamin E, erythrocyte GSH-Px, and reduced glutathione (GSH) values were higher in group C than in groups A and B although LP levels in plasma and erythrocytes were lower in group C than in group A and B. beta-Carotene values did not change in the three groups.In conclusion, VCE supplementation in maximal exercising basketball players may strengthen the antioxidant defense system by decreasing reactive oxygen species (ROS).


Asunto(s)
Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Ejercicio Físico , Peroxidación de Lípido/efectos de los fármacos , Vitamina E/farmacología , Administración Oral , Adolescente , Antioxidantes/administración & dosificación , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/sangre , Baloncesto , Eritrocitos/enzimología , Glutatión/sangre , Glutatión Peroxidasa/metabolismo , Humanos , Masculino , Vitamina A/sangre , Vitamina E/administración & dosificación , Vitamina E/sangre , beta Caroteno/sangre
18.
Neuroreport ; 31(12): 928-935, 2020 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-32576771

RESUMEN

Serotonin (5-HT) has an important role in the pathophysiology of the mood disorders like major depression and anxiety disorders in central nervous system. On the one hand, dorsal raphe nucleus (DRN) neurons send serotonergic projections to almost all brain regions. On the other hand, they affect themselves through 5-HT1A autoreceptors. Many electrophysiological studies have investigated the ionic mechanism of the 5-HTs effect on the DRN neurons of the rat. However, there is no study characterizing the current that mediates the 5-HTs effect on mouse DRN neurons. In the present electrophysiological study, the whole-cell patch-clamp technique was used in the neurons of the DRN from one-month-old Balb/c mice to investigate the effect of 5-HT on the DRN neurons of mice and its ionic mechanism of action. The application of 5-HT resulted in a 14.3 ± 3.1 mV hyperpolarization (n = 9, P < 0.01) of resting membrane potential and 25.7 ± 3.5 pA outward current (n = 7) in the DRN neurons. The reversal potential (E5-HT) of the current induced by 5-HT was close to the potassium equilibrium potential (EK). This current had an inward rectification feature and was blocked by quinine pretreatment (n = 5, P < 0.05). In conclusion, 5-HT inhibits the DRN neurons of mice by inducing a current that is carried by potassium ions through G-protein-coupled inward rectifier potassium channels.


Asunto(s)
Núcleo Dorsal del Rafe/efectos de los fármacos , Neuronas/efectos de los fármacos , Canales de Potasio de Rectificación Interna/farmacología , Serotonina/farmacología , Animales , Proteínas de Unión al GTP/metabolismo , Potenciales de la Membrana/efectos de los fármacos , Ratones
19.
Eur J Pharmacol ; 882: 173163, 2020 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-32485244

RESUMEN

Oxidative stress-induced Ca2+ permeable transient receptor potential melastatin 2 (TRPM2) channels are expressed at high levels in the brain, appear to link neuronal excitability to cellular metabolism, and are involved in the pathogenesis of neurodegenerative disorders. We aimed to study the electrophysiological properties of TRPM2 channels in stellate cells of the mouse ventral cochlear nucleus (VCN) using molecular, immunohistochemical and electrophysiological approaches. In the present study, the real time PCR analysis revealed the presence of the TRPM2 mRNA in the mouse VCN tissue. Cell bodies of stellate cells were moderately labeled with TRPM2 antibodies using immunohistochemical staining. Stellate cells were sensitive to intracellular ADP-ribose (ADPR), a TRPM2 agonist. Upon the application of ADPR, the resting membrane potential of the stellate cells was significantly depolarized, shifting from -61.2 ± 0.9 mV to -57.0 ± 0.8 mV (P < 0.001; n = 21), and the firing rate significantly increased (P < 0.001, n = 6). When the pipette solution contained ADPR (300 µM) and the TRPM2 antagonists flufenamic acid (FFA) (100 µM), N-(p-amylcinnamoyl) anthranilic acid (ACA) (50 µM) and 8-bromo-cADP-Ribose (8-Br-cADPR) (50 µM), the membrane potential shifted in a hyperpolarizing direction. ADPR did not significantly change the resting membrane potential and action potential firing rate of stellate cells from TRPM2-/- mice. In conclusion, the results obtained using these molecular, immunohistochemical and electrophysiological approaches reveal the expression of functional TRPM2 channels in stellate neurons of the mouse VCN. TRPM2 might exert a significant modulatory effect on setting the level of resting excitability.


Asunto(s)
Núcleo Coclear/fisiología , Neuronas/fisiología , Canales Catiónicos TRPM/fisiología , Adenosina Difosfato Ribosa/farmacología , Animales , Núcleo Coclear/metabolismo , Femenino , Masculino , Ratones Endogámicos BALB C , Ratones Noqueados , Neuronas/metabolismo , Canales Catiónicos TRPM/agonistas , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismo
20.
J Membr Biol ; 231(2-3): 57-64, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19838617

RESUMEN

Acetaminophen, an analgesic and antipyretic drug, rescues neuronal cells from mitochondrial redox impairment and reactive oxygen species (ROS). Excessive administration of acetaminophen above the recommended daily dose range has some negative effects on the brain. We investigated the effects of different doses of acetaminophen on Ca(2+)-ATPase and the antioxidant redox system in rats. Seventy rats were randomly divided into seven equal groups. The first was used for the control. One dose of 5, 10, 20, 100, 200, and 500 mg/kg acetaminophen was intraperitoneally administered to rats constituting the second, third, fourth, fifth, sixth, and seventh groups, respectively. After 24 h, brain cortical samples were taken and brain microsomal samples were obtained by ultracentrifugation. Brain and microsomal lipid peroxidation (LP) and brain calcium levels in the sixth and seventh groups were increased compared to control. LP levels in the second, third, and forth groups; brain vitamin E levels; brain and microsomal glutathione peroxidase (GSH-Px); and Ca(2+)-ATPase activity in the sixth and seventh groups were lower than in control, although brain vitamin E concentrations in the second, third, fourth, and fifth groups and microsomal GSH-Px activity in the third and fourth groups were higher than in control. Brain cortical beta-carotene and vitamin A concentrations did not differ in the seven groups. In conclusion, 5-100 mg/kg acetaminophen seems to have protective effects on oxidative stress-induced brain toxicity by inhibiting free radicals and supporting the antioxidant redox system.


Asunto(s)
Acetaminofén/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Microsomas/enzimología , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Animales , Encéfalo/enzimología , Calcio/metabolismo , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Vitamina A/metabolismo , Vitamina E/metabolismo , beta Caroteno/metabolismo
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