RESUMEN
OBJECTIVE: Cerebral ischemia (CI) is a condition in which metabolic stress increases when blood flow is interrupted in a part of the brain, resulting in oxygen and glucose deprivation. It is known that asprosin (Asp), secreted from adipose tissue during fasting, has an effect on some metabolic processes such as apoptosis, autophagy, and glucose metabolism. This study aimed to explain which of the cell death/survival Asp induces in the CI/reperfusion model. MATERIALS AND METHODS: In the study, 48 male Wistar Albino rats were divided into 6 groups: Sham, CI, Asp+CI, CI+Asp, CI+Asp+3-MA, and Asp+CI+3-MA (n=48). CI was created using the intraluminal filament technique for 60 minutes, autophagy inhibitor 3-MA (15 mg/kg/day) and Asp (1 µg/kg/day) injections were administered 3 days before or 3 days during reperfusion. Beclin-1, ATG5, ATG7, p62, Bcl-2, Bax, active-caspase-3, and active-caspase-9 protein levels from brain tissues were determined by the Western-Blot method. The infarct area was determined by triphenyl tetrazolium chloride (TTC) staining. The Kruskal-Wallis' test was used to compare differences between groups. p<0.05 was considered statistically significant. RESULTS: Compared to the Sham group, the increase in ischemic area and the decrease in Beclin-1, ATG-5, ATG-7, Bcl-2, Bax, active-caspase-3 and active-caspase-9 levels in the CI groups are statistically significant (p<0.05). The increase of Beclin-1, ATG-7, Bcl-2, and Bax levels in the Asp groups is statistically significant compared to the CI group (p<0.05). When Asp+CI groups and CI+Asp groups are compared, an increase in Beclin-1 levels in the Asp+CI group and the increase in Bcl-2, Bax, active-caspase-3/9 and ATG-5 levels in the CI+Asp groups are statistically significant (p<0.05). CONCLUSIONS: Asp has protective and therapeutic effects against CI/R damage. While applying Asp before ischemia activates the autophagy pathway more, applying it after ischemia protects the neuronal death/survival balance by activating the apoptosis pathway more.
Asunto(s)
Lesiones Encefálicas , Infarto Cerebral , Masculino , Ratas , Animales , Caspasa 3 , Caspasa 9 , Beclina-1 , Proteína X Asociada a bcl-2 , Ratas Wistar , Apoptosis , AutofagiaRESUMEN
OBJECTIVE: This study aimed to elucidate the possible effects of the acute/long-term infusion of glucagon in the brain as the regulatory role on the endocrine secretions of the pancreas. MATERIALS AND METHODS: Ninety male Wistar albino rats were divided as Control, artificial Cerebrospinal Fluid (aCSF) (120 min), Glucagon (120 min), pancreatic denervation (PD)+aCSF (120 min), PD+Glucagon (120 min), aCSF (7 days), Glucagon (7 days), PD+aCSF (7 days) and PD+Glucagon (7 days). Glucagon and solvent (aCSF) were administered after pancreatic denervation (PD) by Hamilton syringe and osmotic mini pump (1 µg/10 µl/min) in the third ventricle of the brain. RESULTS: Acute intracerebroventricular (icv) administration of glucagon resulted in an elevation of glucagon levels and a concurrent reduction in blood glucose levels. Furthermore, in both the PD+aCSF (7 days) and PD+Glucagon (7 days) groups, there was a notable decrease in propiomelanocortin (POMC) and agouti-related protein (AgRP). Significant changes were observed in feed consumption and body weight, as well as pancreatic glucagon levels, with a simultaneous decrease in insulin levels in the PD (7 days), Glucagon (7 days), and PD+Glucagon (7 days) groups. These alterations were statistically significant when compared to the control group (p<0.05). CONCLUSIONS: The research outcomes established that pancreas-secreted glucagon functions as a neurohormone within the brain, activating central pathways linked to blood glucose regulation. The presence of glucagon led to a decrease in POMC levels. Surprisingly, this reduction in POMC resulted in the suppression of AgRP. Contrary to expectations, the suppression of AgRP led to an increase in food intake rather than a decrease. As already highlighted in the results section, it was emphasized that POMC may play a more significant role than AgRP in influencing feeding behavior.
Asunto(s)
Glucemia , Glucagón , Ratas , Animales , Masculino , Proteína Relacionada con Agouti/metabolismo , Glucemia/metabolismo , Proopiomelanocortina/metabolismo , Sistema Nervioso Central , Homeostasis , Ratas Wistar , NeurotransmisoresRESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disease. This study was performed to determine the possible relationship between melatonin, which is known to play a role in the neuro-protective mechanism in AD, and fasciculation and elongation protein zeta 1 (FEZ1). Thirty male rats were included and separated into 3 groups (n = 10) as vehicle (artificial cerebrospinal fluid), streptozotocin (STZ) and STZ+melatonin (MLT). Two intracerebroventricular (icv) injections of 3 mg/kg STZ were made 48 hours apart. MLT injections were implemented for 14 days (ip; 10mg/kg/day). The Morris Water Maze (MWM) test was performed and rats were sacrificed to assess FEZ1 gene expression and protein levels from the hippocampus tissues and serum levels of noradrenaline (NA), dopamine and serotonin were determined from the blood samples. It was determined that the FEZ1/ß-actin protein ratio in the STZ group was significantly higher than that of the Vehicle group (p < 0.05) and in the MLTadministered group, the protein levels were decreased to the levels observed in the Vehicle group. Serum NA levels of STZ and STZ+MLT groups were found to be lower than those in the Vehicle group, while no difference was found regarding dopamine and serotonin levels. These findings show that reversal of increased FEZ1 levels in AD-induced rats with melatonin administration is the evidence of the effect of melatonin through FEZ1 in AD (Tab. 2, Fig. 5, Ref. 67). Keywords: FEZ1, Alzheimer's disease, melatonin, rat, microtubules, mitochondria.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Enfermedad de Alzheimer , Melatonina , Proteínas Adaptadoras Transductoras de Señales/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales/fisiología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Aprendizaje por Laberinto , Melatonina/farmacología , Ratas , EstreptozocinaRESUMEN
In this study, the effects of Mannich bases containing bis-1,2,4-triazole on the levels of in vivo malondialdehyde (MDA) and antioxidant vitamins (A, E, C) were examined in serum, livers and kidneys of rats. DA and vitamin (A, E, C) levels were determined by high performance liquid chromatography (HPLC). Antioxidant effect was investigated by determining the MDA levels in Saccharomyces cerevisiae cells as in vitro. Furthermore, the antitumor effects of compounds were investigated against MCF-7 human breast cancer cells. Interrelations of results among control and compound groups were evaluated using SPSS statistical software package. As a result, some of the compounds showed effective biological activity when compared to control conditions. The test compounds used in this study may be effective for utilization in the selection and design of model compounds for further studies.
Asunto(s)
Bases de Mannich/farmacología , Triazoles/farmacología , Animales , Antineoplásicos/farmacología , Antioxidantes/farmacología , Supervivencia Celular/efectos de los fármacos , Humanos , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Células MCF-7 , Masculino , Malondialdehído/sangre , Bases de Mannich/síntesis química , Bases de Mannich/química , Ratas , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/metabolismo , Triazoles/síntesis química , Triazoles/química , Vitaminas/metabolismoRESUMEN
In this study, we investigated the effects of polychlorinated biphenyls (PCBs) and organochlorinated pesticides on the serum levels of luteinising hormone (LH), follicle stimulating hormone (FSH) and weights and histomorphometry of uterine tissue in immature female rats using uterotrophic assay. A total of 36 rats were randomly divided into six groups (n = 6 per group) as control, oestradiol (E2, 100 µg/kg), PCB 180, Aroclor 1221, endosulfan and mirex at 10 mg/kg dosage. After 3 days of injections (subcutaneous), animals were decapitated and blood samples were collected. Uteri were dissected, weighed out and then fixed in 10% formaldehyde. They were processed for histomorphometry. The serum levels of LH and FSH were determined by enzyme immunoassay. Uterine weight was significantly increased by E2 and reduced by mirex (p < 0.001 and p < 0.05, respectively). Total volume of uterus was significantly raised by E2, Aroclor 1221 and endosulfan compared with that of the control group (p < 0.01). The ratio of epithelium was significantly increased by E2, PCBs and pesticides (p < 0.01). The uterine cavity ratio was decreased by aroclor (p < 0.01), PCB 180 and mirex (p < 0.05). The serum levels of LH did not significantly differ among the groups but the levels of FSH were decreased by PCB 180 and endosulfan (p < 0.05 and p < 0.01, respectively). These findings suggest that PCB 180, Aroclor 1221 and endosulfan may be estrogenic in immature uterotrophic assay.
Asunto(s)
Estrógenos/farmacología , Hidrocarburos Clorados/farmacología , Plaguicidas/farmacología , Bifenilos Policlorados/farmacología , Útero/efectos de los fármacos , Animales , Arocloros/farmacología , Femenino , Hormona Folículo Estimulante/sangre , Hormona Luteinizante/sangre , Ratas , Ratas Wistar , Útero/patologíaRESUMEN
We have investigated the role of mu- and kappa-opioid receptors in the central control of preovulatory LH and FSH release in the proestrous rat. Animals were anesthetized with chloral hydrate at 14:00 h on proestrus day. Following femoral artery cannulation, they were mounted in a stereotaxic apparatus. Morphine and U-50488H (benzene-acetamide methane sulphonate) were infused intracerebroventricularly either alone or in combination with naloxone and MR1452, respectively. Controls received sterile saline alone. Blood samples were obtained at hourly intervals between 15:00 h and 17:00 h. Plasma LH and FSH levels were measured by radioimmunoassay. Morphine did not significantly change plasma LH levels at 15:00 h and 16:00 h sampling intervals. A significant increase was observed at 17:00 h compared to the controls (p<0.05). U-50488H significantly increased LH levels at 16:00 h and 17:00 h (p<0.05). The co-administration of naloxone and MR1452 with mu- and kappa-agonist had no significant effect on LH levels at any sampling interval. In all groups, LH levels showed a linear rise over the sampling period between 15:00 h and 17:00 h. None of the treatments significantly altered plasma FSH levels which however, declined towards the end of the afternoon surge. In conclusion, we suggest that the secretion of LH and FSH is differentially regulated by mu- and kappa-opioid receptors. It is thought that in all groups chloral hydrate interfered with the LH surge secretory systems.
Asunto(s)
Analgésicos Opioides/farmacología , Hormona Folículo Estimulante/sangre , Fase Folicular/fisiología , Hormona Luteinizante/sangre , Morfina/farmacología , Proestro/fisiología , 3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclohexil)-bencenacetamida, (trans)-Isómero/farmacología , Analgésicos no Narcóticos/farmacología , Animales , Benzomorfanos/farmacología , Femenino , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Sistemas Neurosecretores/efectos de los fármacos , Sistemas Neurosecretores/metabolismo , Ratas , Receptores Opioides kappa/fisiología , Receptores Opioides mu/fisiologíaRESUMEN
We have investigated the effects of thinner inhalation on serum LH, FSH and testosterone levels together with changes in hypothalamic catecholaminergic system in the male rat. A control group inhaled normal air ventilation. The remaining animals were divided into two groups and exposed to paint thinner in a glassy cage for 15 or 30 d. Toluene concentration (the largest constituent in thinner, 66%) was set at 3000 ppm in the inhalation air. At the end, all animals were decapitated and blood samples obtained. Serum LH and FSH levels were measured by RIA and testosterone by enzyme immunoassay. Following removal of brains on dry ice, medial preoptic area, suprachiasmatic nucleus, median eminence and arcuate nucleus were isolated by micropunch technique. Noradrenaline, 3,4-dihydroxyphenylglycol (DHPG) and dopamine concentrations of these hypothalamic areas were determined by HPLC-ECD. Fifteen-day thinner inhalation significantly suppressed serum LH and testosterone levels in parallel (p<0.001) compared to control group values (LH: 0.77+/-0.07; testosterone: 2.67+/-0.39). Thirty-day exposure markedly decreased LH levels (p<0.001), but surprisingly had no significant effect on testosterone. Serum FSH levels were not significantly altered in either group. Thinner inhalation for 15 or 30 d did not cause any significant change in noradrenaline, DHPG or dopamine concentrations in the hypothalamic regions examined (except in the arcuate nucleus). These results suggest that paint thinner has an anti-gonadotropic effect and may cause long-term endocrine disturbances in the male. It is thought that the hypothalamic catecholaminergic system is not involved in thinner inhibition of LH and testosterone secretion.
Asunto(s)
Catecolaminas/metabolismo , Hormona Folículo Estimulante/sangre , Hipotálamo/efectos de los fármacos , Hormona Luteinizante/sangre , Solventes/farmacología , Testosterona/sangre , Animales , Cromatografía Liquida , Hipotálamo/metabolismo , Técnicas para Inmunoenzimas , Masculino , Radioinmunoensayo , Ratas , Ratas WistarRESUMEN
The effects of pinealectomy and exogenous melatonin (N-acetyl-5-methoxytryptamine) on serum leptin levels were investigated in rats. Exogenous administration of melatonin to intact rats resulted in significant decreases in serum leptin levels (P < 0.05) compared to those of the intact control group. Serum leptin levels were significantly elevated in the pinealectomised rats in comparison to the sham-pinealectomised animals (P < 0.001) and were significantly suppressed by exogenous administration of melatonin compared to those of non-treated pinealectomised rats (P < 0.001). Hormone concentrations in the melatonin-treated pinealectomised group were found to be similar to those seen in the sham-pinealectomised group. These results suggest that pineal gland has an effect on leptin release.
Asunto(s)
Leptina/sangre , Melatonina/farmacología , Glándula Pineal/fisiología , Animales , Masculino , Ratas , Ratas WistarRESUMEN
Opiate abuse has been a matter of serious concern in male adolescents. This study investigates the effects of chronic morphine administration on serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone levels, testicular histology, and body and testes weight in developing male rats. Animals were subcutaneously injected with morphine (5 mg/kg) or saline (1 mL/kg) twice daily for 30 days. Body weight determinations and injections were carried out under light ether anesthesia. At the end of the experiments, the rats were decapitated and blood samples were collected. Serum levels of LH and FSH were measured. Chronic morphine administration significantly decreased decreased serum testosterone (p < .02) and LH (p < .01) levels, but not FSH release compared to controls. Morphine exposure reduced body weight (p < .01), but had no significant effect on the testicular weight. When the testicular tissue was histologically examined, structural features of the seminiferous tubules and Leydig cells were similar in both saline and morphine-treated animals. The results suggest that opiates affect testosterone release through the hypothalamo-hypophyseal-gonadal axis rather than by a local testicular mechanism. Chronic morphine exposure during sexual maturation may have long-term endocrine disturbances in male rats.