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1.
Toxicol Mech Methods ; 34(1): 98-108, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37807854

RESUMO

One of the most important side effects of Doxorubicin (DOX), a chemotherapeutic agent, is nephrotoxicity. The purpose of this study is to determine whether different doses of natural polyphenol Resveratrol (RSV) show antioxidative, anti-inflammatory or antiapoptotic effects in kidney tissue in DOX-induced nephrotoxicity and to detect how nephrin and OTULIN levels are affected in this process. A total of six equal groups made up of the 42 Sprague-Dawley rats utilized in the study (n = 7) were randomly assigned. Except for the control group (no treatment), all treatments were given intraperitoneally to the DOX (15 mg/kg), DOX + RSV I (15 mg/kg DOX+ 1 mg/kg/day RSV), DOX + RSV II (15 mg/kg DOX+ 5 mg/kg/day RSV), RSV I and RSV II groups. Kidney tissues taken from rats sacrificed on the fifteenth day were analyzed biochemically, histologically and immunohistochemically. Accordingly, it was determined that nephrin and OTULIN levels decreased in kidney tissue in DOX-induced nephrotoxicity. Furthermore, DOX caused oxidative stress, inflammation, and apoptosis, as well as histopathological changes in kidney tissue. However, it was observed that DOX-induced changes were regulated by RSV application. RSV was demonstrated to have antioxidant, anti-inflammatory and anti-apoptotic properties in dose-dependent DOX-induced nephrotoxicity. RSV may exert nephroprotective effects by modulating DOX-induced altered nephrin and OTULIN levels.


Assuntos
Antioxidantes , Doxorrubicina , Ratos , Animais , Resveratrol/farmacologia , Ratos Sprague-Dawley , Doxorrubicina/toxicidade , Antioxidantes/metabolismo , Estresse Oxidativo , Anti-Inflamatórios/farmacologia , Apoptose , Rim
2.
Cell Mol Biol (Noisy-le-grand) ; 69(3): 13-22, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37300693

RESUMO

Excessive high fructose corn syrup (HFCS) consumption is known to cause oxidative stress, which induces transient receptor potential melastatin type 2 (TRPM2) channel gating. Oxidative stress-induced TRPM2 gating is suggested to play an important role in neurons, indicating a role for the TRPM2 channel in a variety of neuropsychiatric disorders including depression and anxiety. We investigated the effects of HFCS and chronic immobilization stress (CIS) on TRPM2 channel immunoreactivity, anxiety, and depressive-like behaviors in adult male rats. The male rats (n=8/group) were divided into 4 groups: Control, 20% HFCS (F20), 40% HFCS (F40), and stress. The control group received tap water, and F20 and F40 groups were exposed to HFCS 20% and 40% respectively for 14 consecutive days. Rats in the stress group were subjected to immobilization stress for 3 or 6 hours daily in the first and second weeks to induce CIS. Then, light/dark tests, open field tests (OFT), and tail suspension tests (TST) were performed, respectively. In the light/dark test, the time spent in the dark chamber significantly increased in all groups vs the control group (P<0.01). In support of this result, time spent in the light chamber significantly decreased in all groups vs the control group (P<0.01). Besides, CIS significantly increased depressive-like behavior in the stress group vs the control group (P<0.05). In serum hormone levels, corticosterone (CORT) levels significantly increased in the F40 and stress groups vs the control group (P<0.01). TRPM2 immunoreactivity significantly increased in the hippocampus, prefrontal cortex (PFC), nucleus accumbens (NaC), and amygdala regions by HFCS and CIS treatments. For the first time in the present study,  showed that f increased immunoreactivity of the TRPM2 cation channels may be linked to the anxiety-like behavior induced by HFCS.


Assuntos
Ansiedade , Xarope de Milho Rico em Frutose , Canais de Cátion TRPM , Animais , Masculino , Ratos , Ansiedade/induzido quimicamente , Xarope de Milho Rico em Frutose/efeitos adversos , Estresse Oxidativo , Ratos Wistar , Canais de Cátion TRPM/metabolismo
3.
Turk J Med Sci ; 53(6): 1817-1824, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38813488

RESUMO

Background/Aim: Surfactant is a surface-active substance that, in addition to its detergent effect, also has effects that reduce inflammation and fibrosis. Because of these effects, it was aimed herein to investigate the effect of intraperitoneal surfactant application on preventing postoperative peritoneal adhesion formation in a uterine horn adhesion model. Materials and methods: Twenty-one Wistar albino rats were randomly divided into 3 groups (G1-G3), as follows: G1 (n = 7): control group. The abdomen was opened and then closed; G2 (n = 7): adhesion group. The abdomen was opened. Then, a 2-cm linear incision was made over the right uterine horn, 2 mL of isotonic saline was administered intraperitoneally, and the abdomen was closed; and G3 (n = 7): treatment group. The abdomen was opened, a 2-cm linear incision was made over the right uterine horn, 2 mL (70 mg/kg) of surfactant was administered intraperitoneally, and the abdomen was closed. After 15 days, the rats were euthanized, the abdomens were reopened, and adhesion scoring was performed. After the right uterine horns were removed and fixed with 10% formalin, appropriate sections were taken from the traumatized tissue, stained with Masson's trichrome, and fibrosis and inflammation scoring were performed. Results: The adhesion area and intensity were significantly higher in G2 than in G1 and G3 (p = 0.001) and were similar in G1 and G3 (p = 0.165). While fibrosis and inflammation were significantly higher in G2 than in G1 and G3 (p = 0.001), there was no difference between G1 and G3 (p = 0.5). Conclusion: Intraperitoneal surfactant administration at a dose of 70 mg/kg was found to be effective in preventing intraabdominal adhesion formation in a rat uterine horn model.


Assuntos
Complicações Pós-Operatórias , Ratos Wistar , Tensoativos , Animais , Aderências Teciduais/prevenção & controle , Feminino , Tensoativos/farmacologia , Tensoativos/administração & dosagem , Ratos , Complicações Pós-Operatórias/prevenção & controle , Injeções Intraperitoneais , Útero/efeitos dos fármacos , Modelos Animais de Doenças
4.
Turk J Med Sci ; 53(6): 1658-1666, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38813496

RESUMO

Background/aim: By applying humanin (HN) before myocardial infarction (MI), its protection in myocardial injury and the possible roles of its cellular mechanism in the Notch pathway were investigated. Materials and methods: The study was carried out at Firat University Experimental Research Center (12/24/2018-12/23/2019). Spraque-Dawley rats were divided into 10 groups: I (control) (n = 6), II (HN 6 h) (n = 6), III (HN 24 h) (n = 6), IV (HN day 7) (n = 6), V (MI 6 h) (n = 7), VI (MI 24 h) (n = 7), VII (MI day 7) (n = 7), VIII (MI+HN 6 h) (n = 7), IX (MI+HN 24 h) (n = 7), and X (MI+HN day 7) (n = 7). To create MI, 200 mg/kg of isoproterenol (ISO) was administered to the rats subcutaneously. Moreover, 252 µg/kg of HN was given intraperitoneally (ip) to the rats on its own and before MI. Molecular parameters Notch1, Notch2, Hes1, Hes2, Jagged1, Jagged2, DLL1, and DLL4 were examined using polymerase chain reaction in the heart tissue, Notch1, Hes1, and DLL4 were examined using western blot, while heart tissue was taken for histochemical examinations. Results: The mRNA expression levels of the Notch signaling members (Notch1, Notch2, Hes1, Hes2, Jagged1, Jagged2, DLL1, and DLL4) tended to decrease after MI. The Notch signaling members increased more significantly, especially toward day 7 after HN application before MI. In the western blot anylyses, the Notch1, Hes1, and DLL4 protein levels increased significantly toward day 7 in the groups given HN before MI. Moreover, the serum AST, LDH, CK-MB, and troponin I levels tended to decrease with the application of HN before MI and there was a significant decrease in edema, hemorrhage, and mononuclear cells in the heart tissue at 24 h post-MI and fibrosis on day 7 post-MI. Conclusion: HN administration before MI has a cardioprotective effect on rats via the Notch signaling pathway.


Assuntos
Infarto do Miocárdio , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Infarto do Miocárdio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ratos , Masculino , Receptores Notch/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Modelos Animais de Doenças
5.
Andrologia ; 53(2): e13954, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33372325

RESUMO

Male infertility is a global health problem, and the underlying molecular mechanisms are not clearly known. Ion channels and microRNAs (miRNAs), known to function in many vital functions in cells, have been shown to play a significant role in male infertility through changes in their expressions. The study aimed to evaluate the alterations of testicular and/or spermatozoal potassium voltage-gated channel subfamily J member 11 (KCNJ11), Cystic fibrosis transmembrane conductance regulator (CFTR), miR-let-7a and miR-27a expressions in carbamazepine-related male infertility. Here, we showed that carbamazepine reduced sperm motility, increased abnormal sperm morphology, and impaired hormonal balance as well as increased relative testis weight and decreased relative seminal vesicle weight. On the other hand, downregulated KCNJ11 and upregulated miR-let-7a expressions were determined in testis (p < .05). Also, downregulated KCNJ11 and upregulated CFTR and miR-27a expressions were found in spermatozoa (p < .05). Interestingly, altered testicular KCNJ11 and miR-let-7a expressions were correlated with decreased sperm motility and elevated sperm tail defect. Besides, spermatozoal CFTR and miR-27a expressions positively correlated with sperm tail defects. The results indicated a significant relationship between ion channel and/or miRNA expression alterations and impaired sperm parameters due to carbamazepine usage.


Assuntos
MicroRNAs , Motilidade dos Espermatozoides , Carbamazepina/efeitos adversos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Humanos , Masculino , MicroRNAs/genética , Espermatozoides , Testículo
6.
Turk J Med Sci ; 51(2): 787-795, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33237659

RESUMO

Background/aim: Ovarian hyperstimulation syndrome (OHSS) is a complication of ovarian stimulation with increased vascular endothelial growth factor (VEGF) and vascular permeability in the ovarian tissue. Transient receptor potential melastatin 2 (TRPM2) is known to be associated with angiogenesis and vascular permeability. In this experimental study, we aimed to investigate the activity of TRPM2 in the development of OHSS. Materials and methods: Fourteen immature female rats were divided into two groups. Group 1 was the control group, and Group 2 was the OHSS group that was exposed to 10 IU of subcutaneous application of FSH for four days and 30 IU of human chorionic gonadotropin (hCG) on the 5th day. At the end of the experiment, the ovaries were removed. The right ovarian tissues were stored in 10% formol for histopathological and immunohistochemical examination. The left ovarian tissues were stored at ­80 °C for biochemical examinations. VEGF, tumor necrosis factor-alpha (TNF­α) and malondialdehyde (MDA) levels were measured in the ovarian tissue. Congestion, edema, apoptosis and TRPM2 immunoreactivity were evaluated. Results: There was a significant increase in ovarian weight in the OHSS group compared to the control group. There was a significant increase in congestion, edema, apoptosis and TRPM2 immunoreactivity in the OHSS group. A significant increase in tissue levels of VEGF, TNF­α and MDA was also found in the OHSS group compared to the control group. Conclusion: As a result of our experiment, it was found that increased TRPM2 immunoreactivity on hyperstimulated rat ovary may be the reason or result of edema and congestion. Further studies are needed to discuss our results.


Assuntos
Síndrome de Hiperestimulação Ovariana/fisiopatologia , Canais de Cátion TRPM , Canais de Potencial de Receptor Transitório , Animais , Feminino , Malondialdeído/sangue , Malondialdeído/metabolismo , Ratos , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Turk J Med Sci ; 51(5): 2727-2733, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34110724

RESUMO

BACKGROUND: Necrotizing enterocolitis (NEC) is a commonly seen life-threatening condition in newborns characterized by ischemic necrosis. This study aimed to investigate anakinra's effects, an interleukin-1 receptor antagonist, on oxidative stress, inflammation, and tissue necrosis in an NEC rat model. METHODS: Forty Wistar albino pups were divided into four groups randomly as follows; group 1, control group; group 2, anakinra-treated control group; group 3, NEC group; and group 4, NEC and anakinra treatment group. The rats were given hyperosmolar formula feeding, and they were exposed to hypoxia after cold stress at +4 °C and oxygen in order to create the NEC model. On the 4th day of the experiment, the pups were decapitated, and the intestinal tissues were resected for biochemical and histopathologic examination. RESULTS: Microscopic injury scores and apoptotic indexes were higher in group 3 than the control group (p < 0.001, p = 0.002, respectively), and there was a significant decrease after anakinra. Interleukin 1ß and caspase-3 levels increased with NEC and decreased significantly after administration of anakinra (p = 0.006, p = 0.004, respectively). Malondialdehyde and glutathione peroxidase levels also increased compared with the control group (p = 0.019, p = 0.002, respectively). DISCUSSION: In this experimental study, we found that anakinra had antiinflammatory and antioxidant effects and was protective against intestinal injury and apoptosis.


Assuntos
Enterocolite Necrosante , Ratos , Animais , Enterocolite Necrosante/tratamento farmacológico , Enterocolite Necrosante/patologia , Animais Recém-Nascidos , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Ratos Wistar , Modelos Animais de Doenças , Necrose
8.
Andrologia ; 52(10): e13778, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32725937

RESUMO

The effect of verapamil, a calcium channel blocker, on male fertility in terms of ion channel and miRNA gene expressions in testis/spermatozoa was evaluated in this study. Rats were divided into sham and verapamil groups (n = 15). Verapamil was performed orally for 60 days. Sperm parameters and levels of serum follicle-stimulating hormone (FSH), luteinising hormone (LH) and testosterone (T) hormones were analysed. Alterations of microRNA (miRNA) and ion channel gene expressions in spermatozoa/testis were detected by using qPCR. Verapamil treatment reduced sperm concentration. Increased serum FSH, LH and T hormone levels were detected. Upregulated transient receptor potential cation channel subfamily V member 5 (TRPV5) and potassium voltage-gated channel subfamily J member 11 (KCNJ11) gene expressions and downregulated miR-let-7b, miR-10a, miR-320 and miR-760 expressions were found in testis of verapamil group. However, upregulated anoctamin 1 (ANO1), ATP-binding cassette subfamily C member 9 (ABCC9), miR-27a and miR-130a expressions and downregulated miR-20a, miR-92a, miR-132, miR-320 and miR-760 expressions were detected in spermatozoa. In addition, these altered gene expressions were found to be associated with decreased sperm concentration. The results indicate that the changes in testicular and/or spermatozoal ion channels and miRNA expressions due to verapamil treatment may affect male fertility.


Assuntos
Infertilidade Masculina , MicroRNAs , Animais , Hormônio Foliculoestimulante , Humanos , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/genética , Canais Iônicos , Masculino , MicroRNAs/genética , Ratos , Espermatozoides , Testículo , Testosterona , Verapamil/farmacologia
9.
Turk J Med Sci ; 50(4): 1097-1105, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32394684

RESUMO

Background and aim: To compare the effects of bilateral proximal tubal occlusion and bilateral total salpingectomy on ovarian reserve and the cholinergic system via rat experiment. Materials and methods: Twenty-one adult female rats were randomly divided into the following three groups:G1 (n = 7), sham group;G2 (n = 7), bilateral total salpingectomy group; and G3 (n = 7), bilateral proximal tubal occlusion group. Four weeks later, the abdomen of the rats was opened. The right ovarian tissues were stored in 10% formaldehyde, whereas the left ovarian tissues were stored at ­80 °C in aluminum foil. Serum samples were evaluated for antimullerian hormone. The right ovary was used for histological and immunoreactive examination, and the left ovary was used for tissue MDA analysis. Tissue samples were analyzed for MDA levels with spectrophotometric measurement, apoptosis with TUNEL staining, fibrosis score with Mason trichrome staining, ovarian reserve with HE staining, and cholinergic receptor muscarinic 1 (CHRM1) level with immunoreactivity method. Results: Compared to G1 and G3, the number of corpus luteum with secondary follicles was significantly lower in G2, whereas the number of ovarian cysts and fibrosis and apoptosis scores increased significantly. The CHRM1 immunoreactivity was significantly lower in G2 than in G1 and G3. Conclusions: Compared to the bilateral proximal tubal occlusion performed by using bipolar cautery, bilateral total salpingectomy in rats leads to a significant damage in ovarian histopathology and the cholinergic system.


Assuntos
Sistema Colinérgico não Neuronal , Reserva Ovariana , Salpingectomia/métodos , Esterilização Tubária/métodos , Animais , Hormônio Antimülleriano/sangue , Doenças das Tubas Uterinas/terapia , Feminino , Cistos Ovarianos/patologia , Ratos , Ratos Wistar
10.
Cytokine ; 115: 116-120, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30477987

RESUMO

Myocardial infarction (MI) is one of the most important reason of mortality into worldwide. Visfatin is a novel adipokine which was reported increased in metabolic syndrome and obesity. Moreover, it is known that visfatin increases in aterosclerotic endotelial dysfunction. In our study we want to demonstrate how visfatin changes in isoproterenol (ISO) induced MI. Rats were allocated into 4 groups in which each group included 6 rats in this study. 200 mg/kg ISO was administered into rats except control group to induce MI. I. and II. Group rats in 6th hour, III. Group rats in 24th hour and IV. Group rats in 7th day were decapitated. Visfatin was searched in cardiac tissues of all groups by immunohistochemistry stainning. Visfatin and cardiac markers' levels were measured in serum samples. Serum visfatin levels gradually increased in 6th and 24th hour in MI rats compared to controls. In 7th day visfatin levels decreased to control levels. These changes correlated with serum troponin T levels. These findings were supported by immunohistochemistry stainning of visfatin in cardiac tissues. It has been shown that visfatin could be useful in diagnosing MI and may be a biomarker for cardiac ischemia because of increasing in systemic circulation and cardiac tissues in MI like troponins.


Assuntos
Biomarcadores/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Coração/fisiologia , Isoproterenol/farmacologia , Isquemia Miocárdica/induzido quimicamente , Isquemia Miocárdica/metabolismo , Ratos , Troponina T/metabolismo
11.
Turk J Med Sci ; 49(3): 795-801, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31072075

RESUMO

Background/aim: The purpose of this study was toinvestigate the effects of 10% povidone­iodine (PI) sclerotherapyon ovarian cyst diameter through an experimental study. Materials and methods: To be able to create ovarian cysts, right unilateral salpingectomy was performed on 20 Wistar albino rats. One month after the operation, the abdomens of all rats were reopened. Sixteen rats with macroscopic ovarian cysts were divided randomly into 2 groups consisting of 8 rats. Group 1 (G1): the cyst content was only aspirated. Group 2 (G2): the ovarian cyst was aspirated and then the cystic cavity was irrigated with PI. Abdomens of all rats were closed and 1 month later they were reopened. Tissues of the right ovaries of the rats were embedded in paraffin blocks for histopathological examination. Follicle count, fibrosis, and congestion were evaluated under a light microscope. Results: For G1, there was no difference in cyst diameters before and after aspiration. In G2, a decrease was observed in cyst diameter. There was no difference in ovarian reserve between the 2 groups. When compared with G1, an increase in fibrosis and congestion was determined in G2. Conclusion: Sclerotherapyinto the ovarian cyst for a 5-min period using 10% PI reduces cyst diameter without any change in ovarian reserve.


Assuntos
Cistos Ovarianos/patologia , Ovário/efeitos dos fármacos , Povidona-Iodo/farmacologia , Escleroterapia/métodos , Animais , Feminino , Reserva Ovariana/efeitos dos fármacos , Ovário/patologia , Povidona-Iodo/administração & dosagem , Ratos , Ratos Wistar
12.
Turk J Med Sci ; 49(2): 653-660, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30997980

RESUMO

Background/aim: This study compared TRPM2 and TRPM7 ion channel gene expression and immunohistochemical staining in endometrial hyperplasia and endometrium adenocarcinoma. Materials and methods: Sections were taken from paraffin blocks of 120 patients who were divided into 6 groups as follows: G1 (n = 20), proliferative endometrium (PE); G2 (n = 20), EH without atypia; G3 (n = 20), EH with atypia; G4 (n = 20), stage 1A, grade 1 EC; G5 (n = 20), stage 1A, grade 2 EC; and G6 (n = 20), stage 1A, grade 3 EC. TRPM2 and TRPM7 genes were analyzed with qRT-PCR in paraffin-embedded tissue samples. Under light microscopy, TRPM2 and TRPM7 immunostaining scores of the samples taken from polylysine slides were evaluated. Results: Compared to G1, TRPM2 mRNA gene expression was significantly downregulated in G3 and G5. TRPM2 immunoreactivity scores were similar in all groups. TRPM7 mRNA gene expression was significantly downregulated in G2, G3, and G6 when compared to G1. TRPM7 immunoreactivity scores were similar in G1, G2, and G3, but significantly decreased in G4, G5, and G6 Conclusion: Reduction in TRPM7 ion channel activity may be a progression marker for endometrial hyperplasia regardless of the atypical criteria.


Assuntos
Hiperplasia Endometrial/metabolismo , Neoplasias do Endométrio/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Canais de Cátion TRPM/metabolismo , Biomarcadores/metabolismo , Hiperplasia Endometrial/fisiopatologia , Neoplasias do Endométrio/fisiopatologia , Feminino , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Proteínas Serina-Treonina Quinases/genética , Estudos Retrospectivos , Canais de Cátion TRPM/genética
13.
J Membr Biol ; 251(1): 163-178, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29379989

RESUMO

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.


Assuntos
Núcleo Coclear/efeitos dos fármacos , Núcleo Coclear/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Óxidos S-Cíclicos/farmacologia , Diazóxido/análogos & derivados , Diazóxido/farmacologia , Peróxido de Hidrogênio , Canais KATP/agonistas , Canais KATP/antagonistas & inibidores , Canais KATP/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Canais de Potássio Corretores do Fluxo de Internalização/agonistas , Canais de Potássio Corretores do Fluxo de Internalização/antagonistas & inibidores , Tolbutamida/farmacologia
14.
J Obstet Gynaecol ; 38(5): 686-692, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29564948

RESUMO

The aim of this study was to compare the effects of only aspiration with aspiration and 5% trichloroacetic acid (TCA) application on ovarian cyst size and ovarian reserve. The ovarian cysts of 14 rats that were divided into two groups randomly were investigated after total salpingectomy procedure. G1 was the group of saline application after cyst aspiration, while in G2, after aspiration 5% TCA at half amount of aspiration volume was injected into the cyst and re-aspirated after five minutes. The abdomens of the rats were closed and re-explored after 1 month. The cyst diameters of the rats in each group were measured. Ovaries were removed for histopathological examination. There was no significant difference in cyst diameter in G1 before and after aspiration. In G2, there was a significant decrease in cyst size after TCA application. Ovarian follicle counts were not significantly different between the two groups. In conclusion, application of 5% TCA to the ovarian cysts for five minutes significantly reduces the cyst size. Impact Statement What is already known on this subject: Minimally invasive therapies come into prominence to avoid surgical complications and diminished fertility in the treatment of ovarian cysts. USG-guided aspiration and sclerosis has been reported as cost-efficient and effective treatment methods for localised benign cysts in other organs such as the thyroid, parathyroid, liver, kidney and spleen. It has been shown that sclerotherapy applied to infertile women with ovarian cysts reduces pelvic pain without affecting the number of follicles, term pregnancy and abortion rates, extracted oocytes, embryo quality or hormonal levels when compared to non-ovarian cystic infertile women. TCA is a chemical agent that is topically applied, not systemically absorptive, which causes denaturation of proteins and structural cell death, resulting in coagulation necrosis after chemical cauterisation. For this reason, we used 5% TCA to treat simple ovarian cysts on a rat model. What the results of this study add: In this experimental study, we showed that the application of 5% TCA into the cyst for five minutes - then aspirated - significantly reduced the size of the ovarian cysts. Five percent TCA application did not affect the ovarian reserve. What the implications are of these findings for clinical practice and/or further research: Our study is original because of the fact that to the best of our knowledge, this is the first study about the use of 5% TCA in treatment of ovarian cysts in the literature.


Assuntos
Cistos Ovarianos/terapia , Escleroterapia , Animais , Cáusticos/administração & dosagem , Modelos Animais de Doenças , Feminino , Cistos Ovarianos/patologia , Reserva Ovariana , Ovário/metabolismo , Ovário/patologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ácido Tricloroacético/administração & dosagem
15.
Cell Mol Biol (Noisy-le-grand) ; 63(12): 56-62, 2017 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-29307343

RESUMO

The present study was designed to determine the possible hepatoprotective effects of Salvia cryptantha (black weed) plant extract against carbon tetrachloride (CCl4)-induced hepatic injury in rats. Animals were grouped as follows: control group (Group I), CCl4 group (Group II), olive oil group (Group III), CCl4 + S. cryphantha 200 mg/kg group (Group IV), and CCl4 + S. cryptantha 400mg/kg group (Group V). Rats were injected intraperitoneally with CCl4 diluted in olive oil (50% v/v) at a dose of 1ml/kg body weight.  Bax and Caspase3 were determined by immunohistochemical staining, while apoptotic index was evaluated using TUNEL assay. Total mRNA was isolated from liver tissues, and the levels of BCL2, Caspase3, SOD, CAT, and glutathione peroxidase (GPx) were determined by using PCR, while MDA level were determined using a colorimetric assay. The antioxidant and anti-apoptotic gene transcripts were decreased in all of the control and treatment groups, while Caspase3 levels were not statistically different. The S. cryptantha plant extract treatment was also found to improve SOD, GPx, and catalase levels, while reducing the serum levels of MDA. The extract of S. cryptantha supplementation had a protective effect against CCl4-induced liver damage. S. cryptantha extract as a supplement may be useful as a hepato-protective agent to combat the toxic effects caused by CCl4 and other chemicals.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Antioxidantes/metabolismo , Apoptose , Canfanos , Tetracloreto de Carbono , Caspase 3/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Masculino , Panax notoginseng , Fitoterapia , Substâncias Protetoras/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-Dawley , Salvia miltiorrhiza , Proteína X Associada a bcl-2/metabolismo
16.
J Obstet Gynaecol Res ; 41(3): 418-23, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25331934

RESUMO

AIM: To investigate the effectiveness of intraperitoneal vitamin C (VC) and vitamin E (VE) in the prevention of postoperative adhesion formation in a rat uterine horn model. METHODS: Twenty-eight Wistar albino rats were divided into four groups in which: control group, the abdomen was opened and closed without any intervention; adhesion group, a 2-cm linear incision was performed on the uterine horn and closed; VC group, VC was administrated i.p., and 15 min later a 2-cm incision was performed on the uterine horn and closed; and VE group, VE was administrated i.p., and 15 min later a 2-cm incision was performed on the uterine horn and closed. Re-laparotomy was performed 15 days later. Right uterine horn adhesions were evaluated according to macromorphological characteristics and tissue sections were further examined for fibrosis, angiogenesis and vascular endothelial growth factor (VEGF), type I collagen and malondialdehyde (MDA) scoring. Kruskal-Wallis anova and Mann-Whitney U-test were utilized for statistical analysis. RESULTS: Adhesion area and also strength were significantly lower in the VC group and the VE group compared with the adhesion group. Fibrosis and angiogenesis scores were observed to be significantly higher in the adhesion group compared with the VC group and the VE group. MDA and VEGF immunoreactivity were also found to be significantly lower in the VC group and the VE group compared with the adhesion group. However, there was no significant difference between the VC group and the VE group with respect to all the above parameters. CONCLUSION: Administration of VC or VE i.p. was observed to be effective in the prevention of postoperative adhesion formation in an experimental model.


Assuntos
Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Doenças Uterinas/prevenção & controle , Útero/cirurgia , Vitamina E/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Feminino , Injeções Intraperitoneais , Ratos , Ratos Wistar , Aderências Teciduais/prevenção & controle , Vitamina E/administração & dosagem
17.
J Recept Signal Transduct Res ; 34(4): 317-24, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24646197

RESUMO

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.


Assuntos
Fulerenos/administração & dosagem , Hiper-Homocisteinemia/tratamento farmacológico , Canais de Cátion TRPM/biossíntese , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hiper-Homocisteinemia/genética , Camundongos , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/biossíntese
18.
Mol Biol Rep ; 41(12): 8093-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25195052

RESUMO

In the present study, effects on expression of antioxidant, apoptotic and anti-apoptotic genes (GSR, GRX3, SOD1, RAI-NOS, HSP7, BAX, Bcl-2, CASP3 and MDH1) of substances being used in non-surgical sterilization such as quinacrine, erythromycin and tetracycline were evaluated in over tissue. Moreover, expression of some specific mi-RNA (miR-15b, miR-21, miR34a and miR-98) that playing a role in apoptosis was determined in same tissue. Prospective comparative experimental study. Genetics and Histology laboratory. Total number of 28 Wistar albino 12-14 week old female rats with regular cycles and 200-220 grams in weight. Total RNA was isolated from tissues by using a RNA isolation kit. Gene expression levels were evaluated by Real-Time PCR method. Tubal passage and fibrosis induction in tissues was observed in the histochemical analysis. In the statistical analysis of data Kruskal-Wallis variance analysis and Mann-Whitney U test were used and p < 0.05 were accepted as significant. While the expressions of target genes found to be increased in quinacrine and erythromycin group when compared to control group, this increase was insignificant. In quinacrine group, increase in the SOD1 expression levels was only statistically significant (p < 0.05). Expression levels of miR-15b, miR-21, miR34a and miR-98 microRNAs were found to be up-regulated in all experimental groups, despite this, only the increased expression miR-34 was found as statistically significant when compared to control. Tubal blockage and fibrosis induction scores of quinacrine, erythromycin and tetracycline were significantly higher than control. Results of the present study suggest that the doses treated of quinacrine, erythromycin and tetracycline used in non-surgical sterilization effect poorly the expression of anti-oxidant, apoptotic and anti-apoptotic genes, but the expression of miR-34 playing the role in apoptosis increased after treatment of these substances.


Assuntos
Antioxidantes/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Eritromicina/farmacologia , MicroRNAs/metabolismo , Quinacrina/farmacologia , Esterilização Reprodutiva , Tetraciclina/farmacologia , Animais , Proteínas Reguladoras de Apoptose/genética , Feminino , Expressão Gênica , Glutationa Redutase/efeitos dos fármacos , Glutationa Redutase/genética , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/genética , Estudos Prospectivos , Ratos , Ratos Wistar , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/genética , Superóxido Dismutase-1
19.
Cancer Manag Res ; 16: 377-384, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699653

RESUMO

Purpose: As the normal colon epithelium differentiates into adenoma, invasive cancer and metastatic cancer, the cell acquires new characteristics such as apoptosis, proliferation, differentiation, invasion and metastasis. Many mechanisms are effective in acquiring these qualities. One of these is the regulation of the functioning of ion channels. This study aimed to examine TRPA1 and TRPC1 expression in colorectal adenocarcinomas showing different degrees of differentiation. Patients and Methods: We examined the biopsy specimens of 60 patients diagnosed with colorectal adenocarcinomas, including those of patients with well-differentiated (n = 20), moderately differentiated (n = 20) and poorly differentiated (n = 20) carcinomas. Moreover, 20 biopsy specimens of individuals with normal colonic mucosa were examined. Histoscores were calculated for TRPA1 and TRPC1 based on the extent of diffusion and intensity of immunoreactivity, and these scores were compared statistically. Results: A statistically significant increase in both TRPA1 and TRPC1 immunoreactivity was observed in low-grade and high-grade colon adenocarcinomas compared to the control group (p<0.001). A statistically significant decrease in both TRPA1 and TRPC1 immunoreactivity was observed in high-grade colon adenocarcinomas compared to low-grade colon adenocarcinomas (p<0.001). Conclusion: TRPA1 and TRPC1 immunoreactivites are increased in colorectal adenocarcinoma tissue compared with the healthy tissue. Furthermore, the immunoreactivity decreases as the grade of cancer increases.

20.
Iran J Basic Med Sci ; 27(2): 233-240, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38234666

RESUMO

Objectives: Due to its negative side effects, mainly nephrotoxicity, adriamycin (ADR) is used fairly infrequently. The purpose of this study is to investigate the effects of N-acetyl cysteine (NAC) on the immunoreactivity of spexin (SPX) in the kidney tissues of rats given ADR. Materials and Methods: A total of 28 male Sprague-Dawley rats were randomly assigned to four groups (n=7): control (no intervention), NAC (150 mg/kg/day, administered intraperitoneally), ADR (single dose of 15 mg/kg, administered intraperitoneally), and ADR+NAC (single dose of 15 mg/kg ADR + 150 mg/kg/day NAC, both administered intraperitoneally). The experiment was concluded on the 15th day. Results: The administration of ADR resulted in biochemical and histopathological alterations in the kidney. It was found that ADR treatment led to elevated levels of TOS (total oxidative stress), apoptosis, and SPX. Conversely, when NAC was administered as a treatment, it effectively reduced TOS, apoptosis, and SPX levels. These findings suggest that SPX may contribute to the development of ADR-induced kidney damage. Conclusion: Further investigations are warranted to gain a comprehensive understanding of kidney damage, and specifically to elucidate the role of SPX in this context. Additionally, these studies can pave the way for exploring novel therapeutic strategies targeting SPX to prevent and/or treat the development of kidney damage.

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