RESUMO
In the present study, green synthesis of silver nanoparticles (VNE-AgNPs) via Verbascum nudatum extract was carried out for the first time. The synthesized AgNPs were characterized by different spectral methods such as UV-vis, FTIR, XRD, TEM, and EDAX. According to TEM analyses, the average size range of AgNPs was 17-21 nm, and the dominant peaks in the 111°, 200°, 221°, and 311° planes in the XRD pattern indicated the Ag-NPs FCC crystal structure. FTIR data showed that VNE-AgNPs interacted with many reducing, capping, and stabilizing phytochemicals during green synthesis. VNE-AgNPs had higher antibacterial activity against S. aureus and E. coli bacterial strains with a maximum inhibition zone of 21 and 18 mm, respectively, than penicillin 5 IU, used as a positive control in the study. The cytotoxic effect of VNE-AgNPs appeared at a concentration of 50 µg/mL in L929 cells and 5 µg/mL in cancer (A549) cells. When the impact of VNE-AgNPs and C-AgNPs on inflammation was compared, it was found that VNE-AgNPs increased TNF-α levels (333.45 ± 67.20 ng/mg-protein) statistically (p < 0.05) more than TNF-α levels (256.92 ± 27.88 ng/mg-protein) in cells treated with C-AgNPs. VNE-Ag-NPs were found to have a degradation efficiency of 65% against methylene blue (MB) dye within 3 h.
Assuntos
Nanopartículas Metálicas , Extratos Vegetais , Prata , Nanopartículas Metálicas/química , Prata/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Química Verde , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Humanos , Corantes/químicaRESUMO
Ovarian torsion is one of the most dangerous gynecological emergencies requiring surgery. A total of 50%-90% ovarian torsion cases are caused by physiological cysts, endometriosis, and other benign or malignant ovarian neoplasms. The aim of the study was to investigate the effects of erythropoietin (EPO) treatment on ischemia/reperfusion (IR) injury caused by ovarian torsion/detorsion (T/D) injury. Thirty female Wistar albino rats were divided into five groups as follows: Group I: Control; Group II: Torsion (T); Group III: Torsion/Detorsion(T/D); Group IV: Torsion/Detorsion (T/D) + EPO; Group V: EPO. Sections of the ovaries were evaluated for histopathological changes with hematoxylin and eosin stain, a immunohistochemical assay for caspase 3 expression, and the TUNEL assay for apoptosis. Ovarian sections from torsion/detorsion and torsion groups showed more hemorrhage, vascular congestion, edema, degenerative granulosa, and stromal cells. Fewer histopathological changes were found in EPO and T/D + EPO groups. Caspase 3 and TUNEL positive cells were significantly increased in the torsion/detorsion group as compared with the other groups (p < 0.05). Treatment with erythropoietin decreased the number of caspase 3 and TUNEL positive cells. The results of the study showed that erythropoietin administration is effective for recovery from degenerative changes in the ovary induced by the torsion-detorsion injury.
Assuntos
Eritropoetina , Doenças Ovarianas , Traumatismo por Reperfusão , Animais , Humanos , Ratos , Feminino , Torção Ovariana/tratamento farmacológico , Antioxidantes/farmacologia , Caspase 3 , Anormalidade Torcional/tratamento farmacológico , Anormalidade Torcional/metabolismo , Anormalidade Torcional/patologia , Ratos Wistar , Doenças Ovarianas/tratamento farmacológico , Doenças Ovarianas/metabolismo , Doenças Ovarianas/patologia , Eritropoetina/farmacologia , Epoetina alfa , Traumatismo por Reperfusão/tratamento farmacológico , Isquemia/tratamento farmacológicoRESUMO
BACKGROUND: A neurodevelopmental disease, autism spectrum disorder (ASD) occurs in males three times more commonly than girls. Higher prenatal testosterone exposure may result in autistic-like behaviour in boys, according to earlier research. It is unclear how fetal testosterone affects the development of autism. In this study, we tested the hypothesis that prenatal testosterone exposure in an animal model may result in autistic behaviours by modifying serotonin, dopamine, IGF-1 and oxytocin levels. MATERIALS AND METHODS: Group 1 (control, n = 6) and Group 2 (testosterone undecanoate, n = 6) of female rats were randomly assigned. For 2-3 days during the oestrus cycle, female rats were housed with a reproductive male (three females/one male). On the 10th day of gestation, rats in Group 1 received 1 ml/kg% 0.9 NaCl saline, whereas rats in Group 2 received 250 mg/kg testosterone undecanoate. Until weaning on postnatal day 21 (P21), the mothers were permitted to care for their pups. On P21, 40 littermates-10 male and female for control and 10 male and female from mothers that exposed to testosterone-were arbitrarily split up and housed. On P50, these mature rats were tested for their behaviour. The rats were then sacrificed. The brain tissue was subjected to histological examinations as well as biochemical tests for homovanillic acid (HVA), 5-Hydroxyindoleacetic acid (5-HIAA), oxytocin and insulin-like growth factor-1 (IGF-1). RESULTS: The groups differed significantly in the behavioural examinations (three-chamber social test, passive avoidance learning analysis, open field test), with the testosterone-exposed groups exhibiting autistic symptoms to a higher extent. When compared with the control groups, testosterone exposure caused significant histological changes in the hippocampus CA1 and CA3 areas, including gliosis and cell death of neurons. In the testosterone-exposed groups, HVA, 5-HIAA and IGF-1 tissue expressions in the brain elevated, whereas oxytocin levels reduced. These findings point to a potential connection between neurodevelopmental disorders like ASD and exposure to testosterone during gestation. CONCLUSION: Overall, we revealed that prenatal testosterone exposure led to autistic traits by elevating serotonin, dopamine and IGF-1 levels while lowering oxytocin levels.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Ratos , Masculino , Feminino , Animais , Humanos , Transtorno Autístico/induzido quimicamente , Ratos Wistar , Transtorno do Espectro Autista/metabolismo , Fator de Crescimento Insulin-Like I , Dopamina , Ocitocina , Ácido Hidroxi-Indolacético , Serotonina , Testosterona , Modelos Animais de Doenças , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismoRESUMO
PURPOSE: To evaluate the ameliorative effect of mesenchymal stem cells (MSCs) on acetic acid colitis model via Nrf2/HO-1 pathway in rats. METHODS: In this study, 30 rats were divided into three groups. Acute colitis was induced by rectal administration of 4% solution of acetic acid. MSCs were injected intraperitoneally in the treatment group. RESULTS: Increased levels of tumor necrosis factor-α (TNF-α), pentraxin-3, and malondialdehyde (MDA) in colitis group were revealed biochemically. Increased level of TNF-α and decreased levels of Nrf2 and interleukin-10 (IL-10) were observed in rectum tissues. Increased fibrous tissue proliferation, vascularization and inflammatory cell infiltration were described in the colitis group. Significant improvement was observed in MSCs treated group histopathologically. Increased immunopositivity of TNF-α, vascular endothelial growth factor (VEGF) and CD68 markers was observed in the colitis group cells, and decreased level of this positivity was observed in MSCs treated group. CONCLUSIONS: Biochemical, histopathological and immunohistochemical results strongly support the ameliorative effect of MSCs against acetic induced colitis model via Nrf2/HO-1 pathway in rats.
Assuntos
Colite , Células-Tronco Mesenquimais , Animais , Colite/induzido quimicamente , Colite/terapia , Heme Oxigenase-1/metabolismo , Interleucina-10 , Malondialdeído/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology. In this study, we aimed to determine the ameliorating effects of vardenafil in the ASD rat model induced by propionic acid (PPA) in terms of neurobehavioral changes and also support these effects with histopathological changes, brain biochemical analysis and magnetic resonance spectroscopy (MRS) findings. MATERIALS AND METHODS: Twenty-one male rats were randomly assigned into three groups. Group 1 (control, 7 rats) did not receive treatment. Rats in groups 2 and 3 were given PPA at the dose of 250 mg/kg/day intraperitoneally for 5 days. After PPA administration, animals in group 2 (PPAS, 7 rats) were given saline and animals in group 3 (PPAV, 7 rats) were given vardenafil. Behavioral tests were performed between the 20th and 24th days of the study. The rats were taken for MRS on the 25th day. At the end of the study, brain levels of interleukin-2 (IL-2), IL-17, tumor necrosis factor-α, nerve growth factor, cGMP and lactate levels were measured. In the cerebellum and the CA1 and CA3 regions of the hippocampus, counts of neurons and Purkinje cells and glial fibrillary acidic protein (associated with gliosis) were evaluated histologically. RESULTS: Three chamber sociability and passive avoiding test, histopathological results, lactate levels derived from MRS, and biochemical biomarkers revealed significant differences among the PPAV and PPAS groups. CONCLUSION: We concluded that vardenafil improves memory and social behaviors and prevent loss of neuronal and Purkinje cell through its anti-inflammatory and neuroprotective effect.
Assuntos
Transtorno do Espectro Autista , Fármacos Neuroprotetores , Animais , Ratos , Masculino , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/tratamento farmacológico , Interleucina-2/efeitos adversos , Proteína Glial Fibrilar Ácida/metabolismo , Dicloridrato de Vardenafila/efeitos adversos , Interleucina-17 , Fármacos Neuroprotetores/efeitos adversos , Fator de Necrose Tumoral alfa , Propionatos/efeitos adversos , Anti-Inflamatórios , Fatores de Crescimento Neural/efeitos adversos , Lactatos/efeitos adversos , Modelos Animais de DoençasRESUMO
Purpose: To evaluate the ameliorative effect of mesenchymal stem cells (MSCs) on acetic acid colitis model via Nrf2/HO-1 pathway in rats. Methods: In this study, 30 rats were divided into three groups. Acute colitis was induced by rectal administration of 4% solution of acetic acid. MSCs were injected intraperitoneally in the treatment group. Results: Increased levels of tumor necrosis factor-α (TNF-α), pentraxin-3, and malondialdehyde (MDA) in colitis group were revealed biochemically. Increased level of TNF-α and decreased levels of Nrf2 and interleukin-10 (IL-10) were observed in rectum tissues. Increased fibrous tissue proliferation, vascularization and inflammatory cell infiltration were described in the colitis group. Significant improvement was observed in MSCs treated group histopathologically. Increased immunopositivity of TNF-α, vascular endothelial growth factor (VEGF) and CD68 markers was observed in the colitis group cells, and decreased level of this positivity was observed in MSCs treated group. Conclusions: Biochemical, histopathological and immunohistochemical results strongly support the ameliorative effect of MSCs against acetic induced colitis model via Nrf2/HO-1 pathway in rats.
Assuntos
Animais , Ratos , Colite/veterinária , Ácido Acético/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/fisiologia , Fator 2 Relacionado a NF-E2 , Células-Tronco MesenquimaisRESUMO
Arbutin is one of the active ingredients employed in cosmetics as a skin whitening agent. In the present study, the possible effects of arbutin on breast cancer were determined with human breast adenocarcinoma (MCF-7) cells. α and ß-arbutin cytotoxicity levels in MCF-7 cells were determined with the MTT method. At low (1-10 mM) doses, α-arbutin appears to be more toxic than ß-arbutin. At higher (5-200 mM) and LD50 doses beta arbutin toxicity appears to be higher than alpha arbutin. Thus, the study was continued with ß -arbutin. The effects of low and high doses of ß-arbutin was determined on oxidative stress, genotoxicity, inflammation, apoptosis, proliferation, endoplasmic reticulum stress and estrogen receptor-α in MCF-7 cells. The results demonstrated that the ß-arbutin doses administered to MCF-7 cells did not affect oxidative and endoplasmic reticulum stress in the experimental groups. However, it was found that administration of LD50 dose ß-arbutin induced inflammation in these cells via proinflammatory cytokine levels (TNF-α, IFN-γ and IL-1ß). It was observed that LD10 and LD50 doses of ß-arbutin increased genotoxicity in MCF-7 cells. The gene expression analysis conducted with RT-PCR device and immunocytochemical analysis revealed that ß-arbutin at LD50 dose induced apoptosis in MCF-7 cells via p53 and Caspase 3. Furthermore, it was determined that all ß-arbutin doses inhibited estrogen receptor-α in MCF-7 cells. Considering that arbutin increased the activation of apoptotic Caspase 3 through p53, which was stimulated by genotoxic and inflammatory effects at LD50 dose in MCF-7 cells. Determination of this mechanism behind these effects of ß-arbutin may contribute to the development of a new perspective in treatment.
Assuntos
Anticarcinógenos/farmacologia , Arbutina/farmacologia , Neoplasias da Mama/dietoterapia , Receptor alfa de Estrogênio/metabolismo , Apoptose , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Estresse do Retículo Endoplasmático , Feminino , Humanos , Inflamação , Células MCF-7 , Testes para Micronúcleos , Mutagênicos , Estresse Oxidativo , Transdução de SinaisRESUMO
The development of treatment protocols that can reduce side effects in chemotherapy applications is extremely important in terms of cancer treatment. In this context, it was aimed to investigate the effects of boric acid and borax on cisplatin toxicity (nephrotoxicity) in rats. In the experimental phase, eight groups were formed from rats. Boric acid and borax were given to the treatment groups with three different doses using gavage. On the fifth day of the study, cisplatin (10 mg/kg) was administered to all rats except the control group. At the end of the study, oxidative stress-related (GSH, MDA, PCO, GPx, 8-OHdG), inflammation-related (TNF-α, IL-1ß, IL-18, MCP-1, ICAM, TGF-ß), apoptosis-related (p53, caspase 1, 3, 8, 12, bcl-2, bcl-xL, NFkB), and ER stress-related (GRP78, ATF-6, PERK) basic parameters were analyzed in serum, erythrocyte, and kidney tissues. Kidney tissues were also examined by histopathological and immunohistochemical methods. Borax and boric acid at different doses decreased inflammation and oxidative stress caused by cisplatin toxicity and increased ER stress. As a result of the treatments applied to experimental animals, it was determined that boric acid and borax reduced apoptotic damage in kidney tissue, but the decrease was statistically significant only in 200 mg/kg boric acid-administered group. In the study, low anti-apoptotic effects of borate doses with the anti-inflammatory and antioxidant effect may be due to increased ER stress at the relevant doses. Further studies on the effects of boron compounds on ER stress and apoptotic mechanisms may clarify this issue. Thus, possible side effects or if there are new usage areas of borone compounds which have many usage areas in clinics can be detected.
Assuntos
Apoptose/efeitos dos fármacos , Boratos/farmacologia , Ácidos Bóricos/farmacologia , Citotoxinas/antagonistas & inibidores , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Boratos/uso terapêutico , Ácidos Bóricos/uso terapêutico , Cisplatino/toxicidade , Relação Dose-Resposta a Droga , Inflamação/tratamento farmacológico , RatosRESUMO
The aim of the present study was to investigate the effects of safranal on cisplatin-induced nephrotoxicity and oxidative stress in rats. Adult male Sprague-Dawley rats were randomly divided into five groups. The control group received physiological saline; animals in Group 2 received only safranal and in Group 3 received only cisplatin; 5 days of safranal treatment was performed following administration of cisplatin for the animals in Group 4; 5 days of safranal pretreatment was applied to the animals in Group 5 before administration of cisplatin. Cisplatin (7â mg/kg) was intraperitoneally injected as a single dose and safranal (200â mg/kg) was administered by gavage. Biochemical and histopathological methods were utilized for evaluation of the nephrotoxicity. The concentrations of creatinine and urea in plasma and levels of malondialdehyde (MDA) and glutathione (GSH) as well as total antioxidant status (TAS) and total oxidant status (TOS) were determined in kidney tissue. Administration of cisplatin to rats induced a marked renal failure, characterized with a significant increase in plasma creatinine and urea concentrations. MDA and TOS levels of rats that received cisplatin alone were not significantly different compared with those of the control group, but GSH and TAS levels in the only cisplatin-administered group were significantly decreased. Safranal administration produced amelioration in biochemical indices of nephrotoxicity in both plasma and kidney tissues when compared with the only cisplatin-administered group, pretreatment with safranal being more effective. As a result, safranal treatment might have a protective effect against cisplatin-induced nephrotoxicity and oxidative stress in rat.
Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Cicloexenos/farmacologia , Nefrite/tratamento farmacológico , Substâncias Protetoras/farmacologia , Insuficiência Renal/prevenção & controle , Terpenos/farmacologia , Animais , Cisplatino/antagonistas & inibidores , Creatinina/sangue , Esquema de Medicação , Glutationa/metabolismo , Injeções Intraperitoneais , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Malondialdeído/metabolismo , Nefrite/induzido quimicamente , Nefrite/metabolismo , Nefrite/patologia , Ratos , Ratos Sprague-Dawley , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/metabolismo , Insuficiência Renal/patologia , Ureia/sangueRESUMO
PURPOSE: To investigate the effects of pharmacological delay with insulin-like growth factor-1 (IGF-1) on skin flap survival. METHODS: Thirty Sprague-Dawley rats were submitted to dorsal skin flap (3x9 cm). Seven days before the surgery, the animals were subdivided into three groups of 10 rats. In group 1 (controls), no injection was done. Seven days before the elevation, saline had been injected to the marked skin flap area in group 2 (sham group), and group 3 (experimental group) underwent a pharmacological delay with subcutaneous IGF-1 injections. On the seventh postoperative day, flap area was analyzed for survival. Tissue samples were obtained for histological and biochemical evaluations. RESULTS: Survival rates were 43.55 ± 16%, 21.40 ± 8%, and 43.12 ± 14% in groups 1, 2, and 3, respectively. Differences between group 2 and other groups were statistically significant. No significant difference was detected between all three groups for tissue or plasma vascular endothelial growth factor (VEGF) levels. There was no significant histological difference between groups. CONCLUSION: Although a single injection of insulin-like growth factor-1 (IGF-1) did not significantly increase flap survival, its wound healing features are still encouraging and further meticulously planned studies, especially with repeated applications or controlled-release methods, and combinations with binding protein are required.
Assuntos
Anti-Inflamatórios/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/farmacologia , Retalhos Cirúrgicos/fisiologia , Cicatrização/efeitos dos fármacos , Animais , Anti-Inflamatórios/administração & dosagem , Injeções Subcutâneas , Fator de Crescimento Insulin-Like I/administração & dosagem , Ratos , Ratos Sprague-Dawley , Retalhos Cirúrgicos/irrigação sanguínea , Fatores de Crescimento do Endotélio Vascular/sangueRESUMO
ABSTRACT PURPOSE: To investigate the effects of pharmacological delay with insulin-like growth factor-1 (IGF-1) on skin flap survival. METHODS: Thirty Sprague-Dawley rats were submitted to dorsal skin flap (3x9 cm). Seven days before the surgery, the animals were subdivided into three groups of 10 rats. In group 1 (controls), no injection was done. Seven days before the elevation, saline had been injected to the marked skin flap area in group 2 (sham group), and group 3 (experimental group) underwent a pharmacological delay with subcutaneous IGF-1 injections. On the seventh postoperative day, flap area was analyzed for survival. Tissue samples were obtained for histological and biochemical evaluations. RESULTS: Survival rates were 43.55 ± 16%, 21.40 ± 8%, and 43.12 ± 14% in groups 1, 2, and 3, respectively. Differences between group 2 and other groups were statistically significant. No significant difference was detected between all three groups for tissue or plasma vascular endothelial growth factor (VEGF) levels. There was no significant histological difference between groups. CONCLUSION: Although a single injection of insulin-like growth factor-1 (IGF-1) did not significantly increase flap survival, its wound healing features are still encouraging and further meticulously planned studies, especially with repeated applications or controlled-release methods, and combinations with binding protein are required.
Assuntos
Animais , Ratos , Retalhos Cirúrgicos/fisiologia , Cicatrização/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Retalhos Cirúrgicos/irrigação sanguínea , Fator de Crescimento Insulin-Like I/administração & dosagem , Ratos Sprague-Dawley , Fatores de Crescimento do Endotélio Vascular/sangue , Injeções Subcutâneas , Anti-Inflamatórios/administração & dosagemRESUMO
OBJECTIVE: Ischemia and reperfusion (IR) injury is an important complication of abdominal aortic surgery, and it mainly affects the lower extremities and remote organs. In the present study, we aimed to investigate the possible protective effect of crocin in IR-mediated kidney damage. MATERIALS AND METHODS: A total of 24 adult male Wistar-Albino rats were equally and randomly separated into three groups as follows: sham laparotomy, IR, and IR + crocin. Infrarenal aortic occlusion and reperfusion was applied for 1 and 2 h, respectively. Tissue samples were removed and collected. Biochemical and histopathologic analyses were performed. RESULTS: Urea, blood urea nitrogen, creatinine, renal tissue tumor necrosis factor α, interleukin (IL)-6, IL-18, interferon gamma, IL-1ß, total oxidant status, and oxidative stress index levels were significantly higher in IR group, when compared with other groups. These improvements were also demonstrated with some parameters including total score of histopathologic damage, Tunel, Bax, and Caspase-3 expression levels, and these parameters were prominently higher in the IR group, when compared with the other groups. Nevertheless, Bcl2 expression degree was prominently lower in the IR group than those in the other two groups. CONCLUSIONS: Data established from the present study suggest that crocin can preclude renal damage in infrarenal aortic occlusion models.
Assuntos
Injúria Renal Aguda/prevenção & controle , Aorta Abdominal/cirurgia , Carotenoides/uso terapêutico , Substâncias Protetoras/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Biomarcadores/metabolismo , Esquema de Medicação , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Resultado do TratamentoRESUMO
PURPOSE: T o investigate the possible protective effect of thymoquinone (TQ) in cisplatin (CP) induced myocardial injury. METHODS: A total of 28 adult male Wistar-Albino rats were randomly and equally divided into four groups as follows: Group 1 (control), Group 2 (CP at 15 mg/kg dose), Group 3 (TQ 40 mg/kg/day for two days prior to CP injection and on third day, CP at 15 mg/kg dose was intraperitoneally administered and TQ treatment continued until fifth day) and Group 4 (TQ at 40mg/kg/day dose for five days). RESULTS: There was a significant increment in CP group in terms of congestion, edema and pycnotic nuclei in myocardial fibers, comparing with other groups. TQ group exhibited significant increase in expression of antiapoptotic protein Bcl-2, comparing with CP group (p<0.05). In only CP administered group, expression of antiapoptotic protein Bcl-2 was lowest comparing with other groups. CONCLUSION: Established data indicate that cisplatin is cardiotoxic and thymoquinone may be useful in treating CP-induced cardiac injury.
Assuntos
Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Benzoquinonas/farmacologia , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/prevenção & controle , Cisplatino/toxicidade , Animais , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Benzoquinonas/uso terapêutico , Cardiomiopatias/patologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/patologia , Cardiotoxicidade/prevenção & controle , Coração/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Acute kidney injury (AKI) is a serious condition that can be induced by liver transplantation, major hepatic resection or prolonged portal vein occlusion. The AKI can increase the frequency of postoperative complications. In the current study, we aimed to investigate whether interleukin-18 binding protein (IL-18BP) pretreatment has a protective effect against possible kidney injury-mediated liver ischemia-reperfusion (IR) achieved by Pringle maneuver in an experimental rat model. MATERIALS AND METHODS: A total of 21 Wistar albino rats were included in this study. Animals were equally and randomly separated into 3 groups as follows: Sham (n = 7), IR group (n = 7) and IR + IL-18BP group (n = 7). Serum aspartate transaminase, alanine aminotransaminase and lactate dehydrogenase enzyme activities and serum urea and creatinine levels were determined. Tumor necrosis factor-α, IL-6, IL-1ß, interferon gamma, total oxidant status, total antioxidant status and oxidative stress index were measured in kidney tissue homogenate samples. Histopathological examination and immunohistochemical Caspase-3 staining were applied to examine the general morphologic structure and apoptosis. RESULTS: Renal total oxidant status; oxidative stress index; IL-18 levels; serum aspartate transaminase, alanine aminotransaminase and lactate dehydrogenase activities and creatinine levels were significantly lower in IR + IL-18BP group, when compared with the IR group. Beside this, total antioxidant status levels were remarkably higher in IR + IL-18BP group, when compared with the IR group. The caspase-3 expression degree in IR group was remarkably higher than other groups. CONCLUSIONS: It has been demonstrated that IL-18BP pretreatment may have inflammatory, antioxidant and antiapoptotic effects against AKI induced by hepatic IR.
Assuntos
Apoptose/efeitos dos fármacos , Inflamação , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Alanina Transaminase/efeitos dos fármacos , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Creatinina/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Interferon gama/efeitos dos fármacos , Interferon gama/metabolismo , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Rim/metabolismo , Rim/patologia , L-Lactato Desidrogenase/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Fígado/irrigação sanguínea , Fígado/metabolismo , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Proteínas Recombinantes/farmacologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Ureia/metabolismoRESUMO
PURPOSE: T o investigate the possible protective effect of thymoquinone (TQ) in cisplatin (CP) induced myocardial injury. METHODS: A total of 28 adult male Wistar-Albino rats were randomly and equally divided into four groups as follows: Group 1 (control), Group 2 (CP at 15 mg/kg dose), Group 3 (TQ 40 mg/kg/day for two days prior to CP injection and on third day, CP at 15 mg/kg dose was intraperitoneally administered and TQ treatment continued until fifth day) and Group 4 (TQ at 40mg/kg/day dose for five days). RESULTS: There was a significant increment in CP group in terms of congestion, edema and pycnotic nuclei in myocardial fibers, comparing with other groups. TQ group exhibited significant increase in expression of antiapoptotic protein Bcl-2, comparing with CP group (p<0.05). In only CP administered group, expression of antiapoptotic protein Bcl-2 was lowest comparing with other groups. CONCLUSION: Established data indicate that cisplatin is cardiotoxic and thymoquinone may be useful in treating CP-induced cardiac injury.
Assuntos
Animais , Masculino , Benzoquinonas/farmacologia , Cisplatino/toxicidade , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/prevenção & controle , Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Valores de Referência , Fatores de Tempo , Imuno-Histoquímica , Distribuição Aleatória , Reprodutibilidade dos Testes , Benzoquinonas/uso terapêutico , Resultado do Tratamento , Ratos Wistar , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Cardiotoxicidade/etiologia , Cardiotoxicidade/patologia , Cardiotoxicidade/prevenção & controle , Coração/efeitos dos fármacos , Cardiomiopatias/patologia , Miocárdio/patologia , Antioxidantes/uso terapêuticoRESUMO
BACKGROUND: The aim of this study was to investigate the possible protective effect of interleukin 18-binding protein (IL-18BP) on ischemia-reperfusion (I/R)-induced liver injury in experimental rat models. Liver is one of the most affected organs from I/R process. IL-18 is an important proinflammatory cytokine, which may induce some events such as production of reactive oxygen substances and release of various cytokines. IL-18BP acts as an inhibitor of IL-18. The relationship between IL-18 and IL-18BP has an important place in inflammatory process. MATERIALS AND METHODS: Rats were equally divided into three groups as follows: sham: Hepatic pedicle dissection was done, but hepatic pedicle clamping was not used. I/R: Sixty minutes of ischemia and 2 h of reperfusion were applied. IR + IL-18BP: Recombinant human IL-18BP (100 µg/kg) was administered 30 min before the surgery. Hepatic pedicle was clamped during 60 min of ischemia and 2 h of reperfusion was achieved. RESULTS: Liver enzyme levels were significantly lower in the IR + IL-18BP group, when compared with the I/R group. Serum and tissue levels of tumor necrosis factor-α, IL-6, and IL-18 were considerably lower in the IR + IL-18BP group, when compared with the I/R group, but hepatic interferon-γ and IL1ß levels were not significant. Serum oxidative stress index level was significantly higher in the I/R group, when compared with the IR + IL-18BP group. In immunostaining, it was observed that pathologic changes were lower in IR + IL-18BP group than the I/R group. CONCLUSIONS: IL-18BP exhibited anti-inflammatory, antioxidant, and protective effects in I/R-mediated hepatic injury via regulating some liver enzyme activities and cytokine levels. Additionally, these effects have been verified by histomorphologic examination and oxidative stress markers.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Citocinas/sangue , Avaliação Pré-Clínica de Medicamentos , Imuno-Histoquímica , Fígado/enzimologia , Fígado/patologia , Masculino , Estresse Oxidativo , Ratos Wistar , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/patologiaRESUMO
AIM: The aim of this study was to evaluate the effects of calcium channel blocker (CCB) amlodipine (AML), platelet rich plasma (PRP), and a mixture of both materials on bone healing. MATERIALS AND METHODS: Fifty-six male Wistar rats were randomly divided into four groups: group A, tibia defect model with no treatment; group B, tibia defect model treated with AML, 0.04 mg daily by oral gavage; group C, tibia defect model treated with local PRP; group D, tibia defect model treated with local PRP and AML, 0.04 mg daily by oral gavage. RESULTS: At day 21, bone healing was significantly better in groups C and D compared to group A (P<0.05), but comparisons showed no statistically significant difference in group B (P>0.05). At day 30, groups B and C showed no statistically significant difference (P>0.05) compared to group A, but bone healing in group D was significantly better than in group A (P<0.05). Statistically, AML did not affect alkaline phosphatase (ALP) activity at 21 and 30 days (P>0.05), but PRP and AML + PRP increased ALP activity statistically (P<0.05). CONCLUSION: It can be concluded that AML had neither a positive nor a negative effect on bone healing, but when used in combination with PRP, it may be beneficial.
Assuntos
Anlodipino/farmacologia , Regeneração Óssea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Plasma Rico em Plaquetas , Cicatrização/efeitos dos fármacos , Anlodipino/administração & dosagem , Animais , Bloqueadores dos Canais de Cálcio/administração & dosagem , Terapia Combinada , Masculino , Ratos , Ratos WistarRESUMO
PURPOSE: Hemorrhagic cystitis (HC) is the most common urotoxic side effect of cyclophosphamide (CP). The aim of this study was to compare the classical efficacy of mesna (2-mercaptoethane sulfonate sodium) with three different doses of resveratrol (RES) on cyclophosphamide-induced HC in rats. METHODS: Forty-six male Sprague-Dawley rats were divided into six groups. Group 1 served as a negative control (sham). Five groups received a single dose of cyclophosphamide (150 mg/kg) intraperitoneally at the same time. Groups 2, 3, 4, 5, and 6 received only CP, CP + 20 mg/kg RES, CP + 40 mg/kg RES, CP + 80 mg/kg RES, and CP + classical protocol of three doses of mesna (30 mg/kg three times), respectively. Antioxidants, cytokines, and malondialdehyde levels were measured in all groups. In addition, histopathological alterations in tissues were examined. RESULTS: CP administration induced severe HC with marked edema, hemorrhage, and inflammation in group 2. RES 20 mg/kg showed meaningful protection against bladder damage compared to the control group. It was seen that RES 40 mg/kg gave weaker protection but RES 80 mg/kg was not found to be effective. CONCLUSION: In conclusion, marked bladder protection was found in 20 and 40 mg/kg RES applications compared to the control group, but this protection was weaker than with mesna.