RESUMEN
Chronic tobacco use can lead to liver damage and inflammation due to the accumulation of various toxins in the body. This study aimed to investigate the correlation between the molecular mechanisms of nicotine-induced liver injury, the caspase cascade, and the Akt/NF-κB signaling pathway, as well as the protective effects of dexpanthenol (DEX). Male rats were subjected to intraperitoneal injections of nicotine at a concentration of 0.5 mg/kg/day and/or DEX at a concentration of 500 mg/kg/day for 8 weeks. After the treatment period, liver function tests were conducted on serum samples, and tissue samples were analyzed for protein levels of Akt, NF-κB, Bax, Bcl-xL, Caspase-3, and Caspase-9, along with histopathological changes. Additionally, assessments of oxidative stress markers and proinflammatory cytokines were carried out. Nicotine administration led to elevated levels of IL-6, IL-1ß, MDA, TOS, and oxidative stress index, accompanied by decreased TAS levels. Moreover, nicotine exposure reduced the p-Akt/Akt ratio, increased NF-κB, Bax, Caspase-3, and Caspase-9 protein levels, and decreased the antiapoptotic protein Bcl-xL levels. DEX treatment significantly mitigated these effects, restoring the parameters to levels comparable to those of the control group. Nicotine-induced liver injury resulted in oxidative stress, inflammation, and apoptosis, mediated by Bax/Bcl-xL, Caspase-3, Caspase-9, and Akt/NF-κB pathways. Conversely, DEX effectively attenuated nicotine-induced liver injury by modulating apoptosis through NF-κB, Caspase-3, Caspase-9, Bax inhibition, and Bcl-xL activation.
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Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Nicotina , Ácido Pantoténico , Animales , Masculino , Ratas , Antiinflamatorios/farmacología , Apoptosis , Proteína X Asociada a bcl-2/metabolismo , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , FN-kappa B/metabolismo , Nicotina/efectos adversos , Estrés Oxidativo , Ácido Pantoténico/análogos & derivados , Ácido Pantoténico/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Methotrexate is a familiar chemotherapeutic preferred in a wide range of clinical fields such as leukemia, psoriasis, rheumatoid arthritis, neoplastic and autoimmune disorders. However, methotrexate therapy has limitations as it causes severe side effects from which liver damage is the most important one. Several antioxidant compounds have been studied against methotrexate related liver toxicity, but dexpanthenol has not been experienced. Vitamin B5-derived dexpanthenol is a usual therapeutic having a potent anti-inflammatory and antioxidant effect. In this study, we aimed to evaluate the ameliorating effect of dexpanthenol against methotrexate-induced hepatotoxicity. We performed our experiments on Wistar albino rats divided randomly into four groups involving control, dexphantenol, dexpanthenol + methotrexate and methotrexate applied animals. After this experimental work on rats, for the first time, we showed dexpanthenol improvement effect on ROS-caused hepatotoxicity initiated by methotrexate administration in terms of liver tissue antioxidant/oxidant enzymes, liver function tests, and histological changes. We suggest that dexpanthenol might be applied during methotrexate treatment in order to reduce the liver toxicity. However, further studies are needed to find out the optimal dose regimen and to understand the mechanism of action.
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Antioxidantes , Enfermedad Hepática Inducida por Sustancias y Drogas , Animales , Ratas , Antioxidantes/farmacología , Antioxidantes/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Hígado , Metotrexato/toxicidad , Estrés Oxidativo , Ratas WistarRESUMEN
BACKGROUND AND AIMS: Endothelial nitric oxide synthase gene polymorphisms play a role in some pathophysiological processes. In this study, the possible effects of endothelial nitric oxide synthase gene polymorphisms on ureteral stone disease in patients who were admitted to the emergency department with severe pain due to renal colic are examined. MATERIALS AND METHODS: The study groups were designed as controls and patients. The control group was formed from the healthy volunteers who applied to the blood center next to the emergency service. The patient group comprised patients who were diagnosed with ureteral stone disease with severe pain. All of the genetic studies were based on extracted peripheral blood samples using the necessary procedures from the Genome and Stem Cell Center at Erciyes University (GENKOK). The data were analyzed with SPSS (IBM, ver 20, United Sate). RESULTS: The study group comprised 62 females and 138 males, and the control group comprised 64 females and 136 males. All of the stones that caused renal colic were found to be localized in the ureters and the ureterovesical junction. The genotypes of the intron 4 polymorphism were found to be as follows: 4a/4a in 10 people, 4b/4a in 115, and 4b/4b in 275 people. The GG genotype of the eNOS-G894T polymorphism was found in 108 patients in the study group and in117 of the healthy individuals. There was no statistically significant difference between the two groups regarding these data. CONCLUSION: Although this study is the first in the literature to examine the relationship between renal colic and endothelial nitric oxide synthase gene polymorphisms, our study demonstrated that no relation was found.
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Óxido Nítrico Sintasa de Tipo III/genética , Polimorfismo Genético/genética , Cólico Renal/genética , Cálculos Ureterales/genética , Adulto , Femenino , Genotipo , Humanos , Masculino , Óxido Nítrico/genética , Dolor/etiología , Estudios ProspectivosRESUMEN
INTRODUCTION: Hepatotoxicity is a major complication of acetaminophen (APAP), a widely used analgesic and antipyretic drug. Resveratrol (RSV) is a naturally occurring diphenol and it has anticancer, antioxidant, and anti-inflammatory properties. OBJECTIVES: In this study, the beneficial effects of RSV on APAP-induced hepatotoxicity was investigated in rats. MATERIALS AND METHODS: Group 1: Ethanol, Group 2: Saline, Group 3: RSV (10 mg/kg/ip), Group 4: APAP (1000 mg/kg/ip/single dose), Group 5: APAP+RSV (20 min after administration of APAP). The rats were sacrificed 24 h after administration of APAP. Light and electron microscopic changes were evaluated. Levels of malondialdehyde (MDA) and glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities were determined in liver tissue. RESULTS: Rats of the ethanol, saline, and RSV groups did not present any histopathological alterations. In the APAP group, we observed vascular congestion, necrosis, inflammation, sinusoidal dilatation, and loss of glycogen content. In the APAP+RSV group, these changes were markedly reduced. iNOS immunostaining showed very weak positive stained hepatocytes the sections of control, saline, and RSV groups. However, in the APAP group, iNOS immunostaining was most evident in pericentral hepatocytes. In the same areas in APAP+RSV group, intensity of iNOS immunostaining decreased. A significant increase in MDA and decreases in GSH level, CAT, and SOD activity indicated that APAP-induced hepatotoxicity was mediated through oxidative stress. Significant beneficial changes were noted in tissue oxidative stress indicators in rats treated with RSV. CONCLUSION: These biochemical, histopathological, and ultrastructural findings revealed that RSV reduced the severity of APAP-induced alterations in liver.
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Acetaminofén/toxicidad , Analgésicos/toxicidad , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Estilbenos/farmacología , Animales , Masculino , Microscopía Electrónica de Transmisión , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , ResveratrolRESUMEN
Dexmedetomidine (dex) is a potent, highly selective and specific α2-adrenoreceptor agonist. This experimental study was designed to investigate protective and therapeutic effect of two different doses of dex, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Male Sprague-Dawley rats were divided into four groups, each including 10 animals: control group, ischemia-reperfusion (I/R) group; treated groups with 10 µg/kg of dex and 100 µg/kg of dex. After removing right kidney of the rats, the left kidney has performed ischemia during 40 min and reperfusion in the following 3 h. The histopathological findings, and also tissue superoxide dismutase (SOD) and catalase (CAT) enzyme activity, malondialdehyde (MDA), glutathione (GSH), serum blood urea nitrogen (BUN), creatinine (Cre) and tumor necrosis factor-alpha (TNF-α) levels were determined. In the I/R group, compared to the control group, levels of BUN, Cre and kidney tissue MDA have increased significantly, SOD, CAT enzyme activity and glutathione levels have decreased significantly. In the dex10 group, compared to the I/R group, levels of Cre and TNF-α have decreased significantly, while the SOD activity has increased significantly. In the dex100 group, compared to the I/R group, levels of BUN, Cre have decreased significantly, while the SOD activity has increased significantly. In the I/R group, there was also extensive tubular necrosis, glomerular damage in the histological evaluation. Dex ameliorated these histological damages in different amounts in two treatment groups. In this study, the protective effects of dex against renal I/R injury have been evaluated by two different amount of doses.
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Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Dexmedetomidina/uso terapéutico , Riñón/irrigación sanguínea , Daño por Reperfusión/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Riñón/patología , Túbulos Renales/patología , Masculino , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/patologíaRESUMEN
INTRODUCTION: Exposure to carbon tetrachloride (CCl4), a well-known toxicant, causes tissue damage by inducing oxidative stress via formation of free radicals. The fundamental structure of the organs of rats and humans is similar, so administration of CCl4 to rats is an accepted experimental model to produce oxidative damage to various tissues including pulmonary tissue. In this study, we evaluated the protective capacity of melatonin and quercetin against CCl4-induced oxidative lung damage in rats. MATERIAL-METHODS: Rats were divided into five groups each containing seven rats as follows: Control group, Olive oil group CCl4 group, CCl4+Melatonin, and CCl4+Quercetin group. The tissue samples were processed by routine histological and biochemical procedures. Sections were stained with Hematoxylin-eosin and Masson's trichrome. Histopathologic damage score was calculated. Malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activities were assayed. RESULTS: The lung sections of control groups showed normal histological characteristics. Fibrosis, interstitial hemorrhage, epithelial desquamation in bronchiole and alveoli, intra-alveolar edema, leukocyte, and macrophage infiltration were observed in lung sections of rats exposed to CCl4 alone. The findings were reduced in the treatments groups. The MDA level in the CCI4 group were significantly higher than in the other groups (p < .001), and the CAT and GSH levels in the CCI4+Mel and CCI4+Quer groups were significantly higher than in the CCI4 group (p < .05). CONCLUSION: In conclusion, we suggest that agents with antioxidant properties such as melatonin and quercetin may have positive effects in the treatment of pulmonary diseases characterized by especially edema, inflammation, and fibrosis.
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Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/prevención & control , Antioxidantes/uso terapéutico , Tetracloruro de Carbono/efectos adversos , Melatonina/uso terapéutico , Quercetina/uso terapéutico , Lesión Pulmonar Aguda/patología , Animales , Tetracloruro de Carbono/farmacología , Catalasa/metabolismo , Modelos Animales de Enfermedad , Femenino , Glutatión/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Malondialdehído/metabolismo , Neumonía/inducido químicamente , Neumonía/patología , Neumonía/prevención & control , Edema Pulmonar/inducido químicamente , Edema Pulmonar/patología , Edema Pulmonar/prevención & control , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/prevención & control , Ratas , Ratas WistarRESUMEN
Dexpanthenol (DEX), a subtype of vitamin B5, plays an important role in anabolic reactions, cellular energy and regeneration in the body. Nicotine has been shown to induce kidney damage through the mechanisms of oxidative stress and apoptosis. The purpose of this study was to investigate the potential protective effects of DEX against nicotine-induced kidney damage through modulation of the AKT/Nrf2/HO-1 signaling pathway. Male rats were intraperitoneally administered with 0.5 mg/kg/day nicotine and/or 500 mg/kg/day DEX for 8 weeks. Following administration, renal function tests were conducted on serum samples, and histopathological examinations and analysis of oxidative stress markers and antioxidant enzymes were performed on tissue samples. Protein levels of Akt, Nrf-2, HO-1, Bcl-xL, and Caspase-9 were also evaluated. Nicotine administration resulted in decreased protein levels of p-Akt, Nrf-2, HO-1, and Bcl-xL and increased Caspase-9 protein levels. In addition, nicotine administration caused an increase in MDA, TOS, and OSI levels and a decrease in GSH, GSH-Px, GST, CAT, SOD, and TAS levels. Additionally, BUN and Creatinine levels increased after nicotine administration. DEX administration positively regulated these parameters and brought them closer to control levels. Nicotine-induced kidney injury caused apoptosis and oxidative stress through Caspase-9 activation. DEX effectively prevented nicotine-induced kidney damage by increasing intracellular antioxidant levels and regulating apoptosis through Bcl-xL activation. These findings suggest that DEX has potential as a protective agent against nicotine-induced kidney damage.
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Antioxidantes , Ácido Pantoténico/análogos & derivados , Proteínas Proto-Oncogénicas c-akt , Masculino , Ratas , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Caspasa 9/metabolismo , Caspasa 9/farmacología , Nicotina/toxicidad , Nicotina/metabolismo , Estrés Oxidativo , Apoptosis , RiñónRESUMEN
PURPOSE: This study investigated the efficacy of ozone therapy (OT) in a rat model of cyclophosphamide-induced hemorrhagic cystitis (HC). METHODS: Forty Wistar Albino male rats were divided into five groups: sham, OT, cyclophosphamide (CP), OT+CP and CP+OT. Hemorrhagic cystitis (HC) was induced by intraperitoneal (i.p) administration a single dose of 100 mg/kg CP. OT was performed once daily for three days. The CP+OT group received OT (0.2 mg/kg) i.p 24 h after CP administration. CP was injected to the OT+CP group the day after the third course of OT. All animals were killed four days after CP administration. Bladder injury and oxidative stress parameters were determined from tissue samples. RESULTS: We found small, but non-statistically significant biochemical and histological changes in the animals treated with OT alone. CP administration induced cystitis, as manifested by a marked loss of urothelial cells, as well as hemorrhaging and edema in the bladder as determined by histopathological examination. It also caused a significant decrease in the endogenous antioxidant compound glutathione (GSH) and elevation of lipid peroxidation, and nitric oxide (NO) and myeloperoxidase (MPO) levels in the rats' urinary bladder tissue. OT was able to ameliorate these changes; however these effects were prominent in the CP+OT group when compared with the OT+CP group.: For example, the NO level in the CP+OT group was 68% of the OT+CP group (p < 0.05). CONCLUSION: OT prevented CP-induced urothelial damage by diminishing bladder oxidative stress, inflammation and NO levels. OT may help to ameliorate bladder damage induced by CP in the clinical setting.
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Ciclofosfamida/uso terapéutico , Ozono , Vejiga Urinaria/efectos de los fármacos , Animales , Glutatión/metabolismo , Masculino , Malondialdehído/metabolismo , Óxido Nítrico/metabolismo , Ratas , Ratas WistarRESUMEN
In this study, we aimed to investigate the effects of pentoxifylline [PTX] and caffeic acid phenethyl ester [CAPE] in D-galactosamine [D-GAL]-induced pulmonary injury in rats. The rats were randomly divided into six groups: control, D-GAL, D-GAL+PTX, D-GAL+CAPE, PTX and CAPE. Each group included eight animals. Lung sections from the control, PTX and CAPE groups had a normal histological appearance. The D-GAL group showed histopathological changes in lung tissue, including haemorrhage, oedema, inter-alveolar septal thickening and widespread infiltration of inflammatory lymphocytes and macrophages. Administration of PTX and CAPE significantly reduced histopathological damage scores in the D-GAL+PTX and D-GAL+CAPE groups compared with the D-GAL group. PTX and CAPE treatment also significantly decreased malondialdehyde levels, increased levels of reduced GSH and increased catalase and superoxide dismutase activity in lung tissue samples. These results indicate that the destructive effects of D-GAL-induced inflammation in the rat lung are significantly reduced following administration of PTX and CAPE.
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Lesión Pulmonar , Pentoxifilina , Ratas , Animales , Pentoxifilina/farmacología , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/patología , Factor de Necrosis Tumoral alfa/farmacología , Superóxido Dismutasa , Galactosamina/toxicidad , Catalasa , Pulmón/patología , Ácidos Cafeicos/farmacología , Malondialdehído , Antioxidantes/farmacologíaRESUMEN
Due to its antioxidant and antimicrobial properties, sulfur dioxide (SO2) is widely used in foods and beverages to prevent the growth of microorganisms and to preserve the color and flavor of fruits. However, the amount of SO2 used in fruit preservation should be limited due to its possible adverse effects on human health. The present study was designed to investigate the effects of different SO2 concentrations in apricot diets on rat testes. Animals were randomly divided into six groups. The control group was fed a standard diet, and the other groups were fed apricot diet pellets prepared with (w/w) 10% dried apricots containing SO2 at different concentrations (1500 ppm, 2000 ppm, 2500 ppm, 3000 ppm, and 3500 ppm/kg) for 24 weeks. After sacrification, testicles were evaluated biochemically, histopathologically, and immunohistopathologically. Our results showed that an apricot diet containing 1500 ppm and 2000 ppm SO2 did not cause significant changes in testis. However, it was determined that tissue testosterone levels decreased as the amount of SO2 (2500 ppm and above) increased. Apricot diet containing 3500 ppm SO2 caused a significant increase in spermatogenic cell apoptosis, oxidative damage, and histopathological changes. In addition, a decrease in the expression of connexin-43, vimentin, and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) was observed in the same group. In summary, the results show that sulfurization of apricot at high concentrations such as 3500 ppm may lead to male fertility problems in the long term through mechanisms such as oxidative stress, spermatogenic cell apoptosis, and inhibition of steroidogenesis.
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Prunus armeniaca , Dióxido de Azufre , Masculino , Humanos , Ratas , Animales , Dióxido de Azufre/análisis , Testículo , Dieta , Frutas/químicaRESUMEN
We investigated the effects of quercetin on cisplatin induced testicular toxicity using histopathological, immunohistochemical and biochemical methods. We used four groups of Wistar albino male: control, quercetin, cisplatin, cisplatin + quercetin. We measured tissue malondialdehyde (MDA) and catalase (CAT) biochemically. We assessed apoptosis as indicated by P63 immunoreactivity. Testis tissues of the control group exhibited normal histology. In the cisplatin group, the diameter of the seminiferous tubule and thickness of the germinal epithelium were decreased compared to the control group. In the cisplatin group, degeneration of the germinal epithelium, cell separation from the basal membrane, giant cell formation, cell loss, atrophy and vacuolization were observed in the seminiferous tubule. We found hyalinization around the seminiferous tubule, intertubule hyalinization and perivascular fibrosis. In the cisplatin + quercetin group, we found that quercetin decreased atrophy, giant cell formation and vacuolization significantly. We found that quercetin exhibited ameliorative effects following cisplatin induced testicular damage.
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Quercetina , Testículo , Animales , Antioxidantes/farmacología , Cisplatino/toxicidad , Masculino , Malondialdehído/farmacología , Estrés Oxidativo , Quercetina/farmacología , Ratas , Ratas WistarRESUMEN
Exposure to various organic compounds including several environmental pollutants and drugs can cause cellular damage through the generation of lipid peroxidation products. Carbon tetrachloride (CCl4) is a potent toxic agent that causes peroxidative degeneration in many tissues. Dexpanthenol (Dxp) is a member of the B complex vitamins that exhibits antioxidant effects against lipid peroxidation products. This study was designed to evaluate the cardioprotective effect of Dxp against CCl4-induced myocardial toxicity in rats. Administration of a single dose of CCl4 caused cardiotoxicity by the increase in lipid peroxidation and histopathological changes (cardiomyocytes degeneration, interstitial edema) in the myocardial tissue. Moreover, CCl4 caused a decrease in lactate dehydrogenase (LDH) and troponin-I immunoreactivities, while significantly increasing tumor necrosis factor-alpha (TNF-α) and caspase-3 immunoreactivities. On the other hand, administration of Dxp improved biochemical, histopathological, and immunohistochemical parameters compared to the CCl4 treated group. Overall, this study suggests that Dxp is effective in inhibiting CCl4-induced lipid peroxidation, and that administration of Dxp may help prevent CCl4 related inflammation, necrosis, and apoptosis on the cardiac tissue.
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Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Tetracloruro de Carbono/metabolismo , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Peroxidación de Lípido , Hígado/patología , Estrés Oxidativo , Ácido Pantoténico/análogos & derivados , RatasRESUMEN
The protective effects of melatonin (Mel) and vitamin E (Vit E) against the negative effects of acetamiprid (Acmp) on testicles, reproductive hormones, and oxidative stress parameters were investigated in the present study. A total of 50 Balb-c male mice were used in 7 groups; 6 mice in the control groups (distilled water, corn oil, ethanol), and 8 in other groups (Acmp, Acmp + Mel, Acmp + Vit E, Acmp + Vit E + Mel). After the experiment, which lasted 21 days, hematoxylin eosin (H&E), periodic acid Schiff (PAS), and caspase-3 immunohistochemical (IHC) staining was performed on the testicular tissues. Also, the tissues were examined ultrastructurally with the transmission electron microscopy (TEM). In the Acmp group, there were decreased seminiferous tubule diameter and epithelial thickness, epithelial degeneration, decreased spermatozoa in the lumen, decreased PAS-positive staining in the seminiferous epithelial basement membrane, edema in the interstitial area, and hydropic degeneration in Leydig cells. Caspase-3 immunoreactivity was higher than in the other groups. TEM examination showed degeneration in tubule cells, lysosomal accumulation in cells of the spermatogenic line, vacuolizations with myelin figures, and necrosis. Hydropic degeneration, electron-dense lipid vacuoles, and chromatolysis were evident in the Leydig cell cytoplasm. In Sertoli cells, electron-dense lysosomal deposits were noted. In biochemical terms, there were decreased tissue glutathione (GSH) and total antioxidant status (TAS), and increased malondialdehyde (MDA) and total oxidant status (TOS). Plasma luteinizing hormone (LH), follicular stimulating hormone (FSH), and testosterone levels were decreased. In the groups with melatonin, vitamin E, and both were applied together, tissue damage, and apoptotic cell death were reduced at both light microscopic and ultrastructural levels. In biochemical terms, there were decreased oxidative parameters and increased hormonal parameters. It was found that vitamin E was more effective in decreasing oxidative parameters and increasing antioxidative parameters when compared to melatonin, and hormonal parameters increased at a higher level in the Acmp + Vit E group than in all groups. As a result, it was found that exposure to Acmp caused damage to testicular tissue, induced oxidative stress in testicles, and decreased plasma LH, FSH, and testosterone levels, and although vitamin E is more effective than melatonin in preventing this damage, both are effective.
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Melatonina , Vitamina E , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Caspasa 3/metabolismo , Electrones , Hormona Folículo Estimulante , Glutatión/metabolismo , Hormona Luteinizante , Masculino , Melatonina/metabolismo , Melatonina/farmacología , Ratones , Ratones Endogámicos BALB C , Neonicotinoides , Estrés Oxidativo , Testículo/metabolismo , Testosterona , Vitamina E/metabolismo , Vitamina E/farmacologíaRESUMEN
Depression is a serious psychological disorder that affects a significant population. We investigated the antidepressant activities of four pyridazinone derivatives that contain the hydrazide moiety using the forced swimming test (FST). The compounds tested exhibited good antidepressant activity compared to duloxetine. The most promising compound was compound 2, which reduced the duration of immobility during FST. The toxic effects of the four compounds on the histomorphology of the liver and stomach tissue also was evaluated.
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Antidepresivos , Natación , Antidepresivos/farmacología , Depresión , Hígado , Estómago , Natación/psicologíaRESUMEN
OBJECTIVES: Epilepsy is a neurological disease that pathologically affects brain functions. The epileptic hippocampus has modified microRNA(miRNA) levels. Therefore, we aimed to evaluate the neuroprotective effect of thymoquinone (TQ) in PTZ-induced epilepsy and to demonstrate the overlap between miRNA and mRNA expression profiles. METHODS: Male adult Wistar albino rats (200-230 g, n = 20) were divided into three groups as control (n = 6), PTZ (n = 7), and TQ + PTZ (n = 7). The PTZ kindling model was created by injecting PTZ in sub convulsive doses to rats on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, and 24 of the study into animals. Clonic and tonic seizures were induced by injecting a convulsive dose of PTZ on day 26 of the study. Rats in the TQ+PTZ group were treated by oral gavage with a 20 mg/kg TQ 2 h before each PTZ injection. The rats in the control group were treated with 0.5 ml saline. Seizure severity was evaluated with the Racine scale. The genes and signaling pathways targeted by miRNAs were determined by bioinformatics analysis. RESULTS: In the rat hippocampus, mature 728 miRNAs were analyzed by microarray and the nine miRNA were verified by quantitative Real-Time PCR. rno-miR-182 and rno-miR-27b-3p were up-regulated in the PTZ group and down-regulated in the TQ + PTZ group. DISCUSSION: In the PTZ kindling epilepsy model, the expression of these two miRNAs was regulated by TQ and exerted a neuroprotective effect by controlling the activities of target genes.
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Epilepsia , Excitación Neurológica , MicroARNs , Fármacos Neuroprotectores , Animales , Benzoquinonas , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Hipocampo , Masculino , MicroARNs/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Pentilenotetrazol/toxicidad , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Convulsiones/metabolismoRESUMEN
OBJECTIVES: Varenicline is a selective partial agonist for the nicotinic acetylcholine receptor a4b2 subtype, which is widely used to treat smoking addiction. However, there is still no data about its potential toxic effects on tissues. In this study, we aimed to determine the varenicline-induced toxicity on reproductive and renal tissues in rats. MATERIALS AND METHODS: Rats were randomly divided into two groups: control (n=10) and varenicline (n=24). Then, rats in each group were sub-divided equally as acute and chronic groups. The control rats were orally given distilled water only. Varenicline was administrated orally as follows: 1st-3rd days 9 µg/kg/day, 4th-7th days 9 µg/kg twice daily, and 8th-90th days 18 µg/kg twice daily. The rats of acute and chronic groups were sacrificed on the 45th and 90th days, respectively. Some tissue markers related to oxidative stress were measured, and sperm characteristics were observed. RESULTS: In the acute group, varenicline led to a significant decrease in SOD activities in both kidney and testis tissues. In the chronic group, varenicline significantly increased MDA and MPO production, and reduced CAT and GPx levels in the kidneys and testes. Also, SOD and GSH levels significantly decreased in the testes. Moreover, sperm characteristics were negatively affected; histopathological deformation was observed in the testes and kidneys in all groups. CONCLUSION: This study showed that varenicline could detrimentally affect the kidneys and testes in both acute and chronic term usage. Further studies will provide more insights into the molecular dynamics of this damage.
RESUMEN
BACKGROUND: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. AIMS: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. STUDY DESIGN: Animal experimentation. METHODS: Forty male Wistar albino rats were divided into five groups: control, stress, stress + standard diet, stress + parsley-added diet and stress + lansoprazole (LPZ) groups. Subjects were exposed to 72 hours of fasting and later immobilized and exposed to the cold at +4 degrees for 8 hours to create a severe stress condition. Samples from the animals' stomachs were arranged for microscopic and biochemical examinations. RESULTS: Gastric mucosal injury was obvious in rats exposed to stress. The histopathologic damage score of the stress group (7.00±0.57) was higher than that of the control group (1.50±0.22) (p<0.05). Significant differences in histopathologic damage score were found between the stress and stress + parsley-added diet groups (p<0.05), the stress and stress + standard diet groups (p<0.05), and the stress and stress + LPZ groups (p<0.05). The mean tissue malondialdehyde levels of the stress + parsley-added group and the stress + LPZ group were lower than that of the stress group (p<0.05). Parsley supported the cellular antioxidant system by increasing the mean tissue glutathione level (53.31±9.50) and superoxide dismutase (15.18±1.05) and catalase (16.68±2.29) activities. CONCLUSION: Oral administration of parsley is effective in reducing stress-induced gastric injury by supporting the cellular antioxidant defence system.
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Estrés Oxidativo/fisiología , Petroselinum/metabolismo , Gastropatías/prevención & control , Estrés Psicológico/complicaciones , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Wistar/metabolismo , Gastropatías/tratamiento farmacológico , Estrés Psicológico/psicologíaRESUMEN
AIM: In recent studies, it has been shown that the Transient Receptor Potential Melastatin-2 Channels (TRPM2) and Phospholipases A2 (PLA2) inhibitors may have a protective effect on neurons. This study was aimed to investigate the protective effect of TRPM2 and PLA2 inhibitor N-(p-amylcinnamoyl) Anthranilic Acid (ACA) in a neurodegenerative model induced by Okadaic Acid (OKA). MAIN METHODS: OKA (200ng/10µl) was administered bilateral intracerebroventricularly as a single injection. KEY FINDINGS: OKA-treated rats showed significant impairments of spatial memory in Morris Water Maze Test. OKA-induced memory-impaired rats showed increased numbers of degenerated neurons and Caspase-3, tau phosphorylated ser396, ß-amyloid positive cells in the hippocampus and cerebral cortex. Furthermore, OKA-treated rats exhibited significantly increased MDA, TNF-α levels, and decreased SOD, GSH-PX enzyme activates and GSH levels of the tissues. ACA administration ameliorated OKA-induced memory impairment in rats. The ACA treatment also increased SOD and GSH-PX enzyme activation and GSH levels, and conversely decreased the levels of MDA, TNF-α. It was found that the numbers of the degenerated neurons and Caspase-3 positive cells of cortex and hippocampus regions were significantly reduced. SIGNIFICANCE: ACA administration attenuates the oxidative stress and neuroinflammation of OKA-induced neurodegeneration; and ameliorates the cognitive decline and neurodegeneration.
Asunto(s)
Corteza Cerebral , Hipocampo , Enfermedades Neurodegenerativas , Ácido Ocadaico/toxicidad , Inhibidores de Fosfolipasa A2/farmacología , Canales Catiónicos TRPM/metabolismo , ortoaminobenzoatos/farmacología , Animales , Caspasa 3/metabolismo , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Hipocampo/metabolismo , Hipocampo/fisiopatología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Enfermedades Neurodegenerativas/inducido químicamente , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/fisiopatología , Enfermedades Neurodegenerativas/prevención & control , Fosfolipasas A2/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Dexpanthenol (Dxp) plays a major role in cellular defense and in repair systems against oxidative stress and inflammatory response and it has not yet been evaluated in treatment of bronchopulmonary dysplasia (BPD). We tested the hypothesis that proposes whether Dxp decreases the severity of lung injury in an animal model of BPD. METHODS: Forty rat pups were divided into four groups: control, control + Dxp, hyperoxia and hyperoxia + Dxp. All animals were processed for lung histology and tissue analysis. The degree of lung inflammation, oxidative and antioxidant capacity was assessed from lung homogenates. RESULTS: Lung injury score and alveol diameter increased in the hyperoxia group (p < 0.001). Median level of malondialdehyde, total oxidant status and oxidative stress indexes was significantly higher in the hyperoxia group compared to the other groups. The median superoxide dismutase activity in the hyperoxia group was notably less than those of control + Dxp and hyperoxia + Dxp groups (p < 0.01). Similarly, lung catalase, glutathione (GSH) peroxidase and reduced GSH activities in the hyperoxia group were significantly lower than other groups. Furthermore, the hyperoxia + Dxp group had lower tumor necrosis factor-α and interleukin-1ß median levels compared to the hyperoxia group (p = 0.007). CONCLUSION: Dxp treatment results in less emphysematous change as well as decrease in inflammation and oxidative stress markers in an animal model of BPD.
Asunto(s)
Lesión Pulmonar/prevención & control , Ácido Pantoténico/análogos & derivados , Animales , Animales Recién Nacidos , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Evaluación Preclínica de Medicamentos , Femenino , Hiperoxia/complicaciones , Pulmón/patología , Lesión Pulmonar/enzimología , Lesión Pulmonar/etiología , Lesión Pulmonar/patología , Masculino , Estrés Oxidativo , Ácido Pantoténico/uso terapéutico , Embarazo , Distribución Aleatoria , Ratas WistarRESUMEN
Developing biocompatible tissue adhesives with high adhesion properties is a highly desired goal of the tissue engineering due to adverse effects of the sutures. Therefore, our work involves synthesis, characterization, adhesion properties, protein adsorption, in vitro biodegradation, in vitro and in vivo biocompatibility properties of xylose-based semisynthetic polyurethane (NPU-PEG-X) bioadhesives. Xylose-based semisynthetic polyurethanes were developed by the reaction among 4,4'-methylenebis(cyclohexyl isocyanate) (MCI), xylose and polyethylene glycol 200 (PEG). Synthesized polyurethanes (PUs) showed good thermal stability and high adhesion strength. The highest values in adhesion strength were measured as 415.0 ± 48.8 and 94.0 ± 2.8 kPa for aluminum substrate and muscle tissue in 15% xylose containing PUs (NPU-PEG-X-15%), respectively. The biodegradation of NPU-PEG-X-15% was also determined as 19.96 ± 1.04% after 8 weeks of incubation. Relative cell viability of xylose containing PU was above 86%. Moreover, 10% xylose containing NPU-PEG-X (NPU-PEG-X-10%) sample has favorable tissue response, and inflammatory reaction between 1 and 6 weeks implantation period. With high adhesiveness and biocompatibility properties, NPU-PEG-X can be used in the medical field as supporting materials for preventing the fluid leakage after abdominal surgery or wound closure.