Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Med Oncol ; 40(1): 60, 2022 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-36565382

RESUMO

In this study, we have investigated the chemotherapeutic potential of titanium dioxide (TiO2) nanoparticles on skin and breast cancer cells. The cells have treated with a 75 µg/ml concentration of titanium dioxide because it is a recommended dose with proven effectiveness in vitro studies and then the cells were exposed to UV-A radiation. The combined effects of titanium dioxide and UV-A radiation on cell viability, cell cycle, plasma membrane, mitochondrial membrane potentials and apoptotic activity of the cells were investigated. The viability of SK-MEL 30 cells was measured by MTT assay and apoptotic activity of cells was determined by Annexin-V FITC/PI staining. As a result of the research, an increase was observed in the viability of cells treated with 75 µg/ml titanium dioxide concentration, while a significant decrease in cell viability was observed for both cell types when UV-A radiation and TiO2 were applied together. The results also showed that the percentage of apoptotic cells increased as a result of UV + TiO2 exposure. Accordingly, it can be said that TiO2 nanoparticles may research as potential chemotherapeutic agents for skin and breast cancers, especially in the presence of UV radiation.


Assuntos
Nanopartículas , Neoplasias Cutâneas , Humanos , Raios Ultravioleta , Titânio/farmacologia
2.
Toxicol Appl Pharmacol ; 433: 115780, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34756876

RESUMO

Ischemia/Reperfusion (I/R) injury is clinically important in many surgical practice including kidney transplantation. It is known that mitochondria have a key role in the intracellular and extracellular signaling pathways of ischemia and reperfusion injury. In this respect, we pointed to explore the probable effects of isolated mitochondria transplantation from MSCs (mesenchymal stem cells), to alleviate ischemia/reperfusion-induced renal injury. Experiments were held on the 48 male Sprague Dawley rats. Groups were divided as Control (C1), I/R-Control (C2), Vehicle-1 (V1), Vehicle-2 (V2), Transplantation-1 (T1) and Transplantation-2 (T2) group. Unilaterally nephrectomy was performed in all groups. In the groups except the control, the left kidneys ischemized for 45 min and then reperfusion was carried out. According to the study groups, isolated mitochondria or vehicle infused into the renal cortex and rats were monitored for 48 h. Following that mentioned procedure, animals were sacrificed and biological samples were taken for physiological, histological and biochemical examinations. The results of present study show that mitochondrial transplantation promoted proliferation and regeneration of tubular cells after renal injury. Moreover, mitochondrial transplantation reduced mitochondrial dynamics-DRP-1 fission protein of tubular cells and reversed renal deficits. Mitochondrial transplantation diminished apoptotic markers including TUNEL and Caspase-3 levels in injured renal cells. Our results provide a direct link between mitochondria dysfunction and ischemia/reperfusion-induced renal injury and suggest a therapeutic effect of transplanting isolated mitochondria obtained from MSCs against renal injury.


Assuntos
Proliferação de Células , Nefropatias/prevenção & controle , Rim/patologia , Transplante de Células-Tronco Mesenquimais , Mitocôndrias/transplante , Dinâmica Mitocondrial , Regeneração , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose , Caspase 3/metabolismo , Células Cultivadas , Dinaminas/metabolismo , GTP Fosfo-Hidrolases , Rim/metabolismo , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas Mitocondriais , Estresse Oxidativo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
3.
Life Sci ; 279: 119669, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34081988

RESUMO

AIMS: Acetaminophen (APAP) toxicity is one of the leading causes of acute liver injury-related death and liver failure worldwide. In many studies, mitochondrial dysfunction has been identified as an important cause of damage in APAP toxicity. Therefore, our study aimed to investigate the possible effects of mitochondrial transplantation on liver damage due to APAP toxicity. MAIN METHODS: APAP toxicity model was implemented by administering a toxic dose of APAP. To demonstrate the efficiency of mitochondria transplantation, it was compared with N-acetylcysteine (NAC) application, which is now clinically accepted. Mitochondrial transplantation was carried out by delivering mitochondria to the liver via the portal circulation, which was injected into the spleen. In our study, the rats were randomly divided into 6 groups as Sham, APAP, Control 1, APAP+mito, Control 2, and APAP+NAC. In the end of the experiment, histological and biochemical analysis were performed and the biodistribution of the transplanted mitochondria to target cells were also shown. KEY FINDINGS: Successful mitochondrial transplantation was confirmed and mitochondrial transplantation improved the liver histological structure to a similar level with healthy rats. Moreover, plasma ALT levels, apoptotic cells, and total oxidant levels were decreased. It was also observed that NAC treatment increased GSH levels to the highest level among the groups. However, mitochondrial transplantation was more effective than NAC application in terms of histological and functional improvement. SIGNIFICANCE: It has been evaluated that mitochondrial transplantation can be used as an important alternative or adjunctive treatment method in liver damage caused by toxic dose APAP intake.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/terapia , Glutationa/metabolismo , Peroxidação de Lipídeos , Mitocôndrias/transplante , Analgésicos não Narcóticos/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
4.
J Biochem Mol Toxicol ; 35(1): e22612, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32870571

RESUMO

The effect of dysfunctional mitochondria in several cell pathologies has been reported in renal diseases, including diabetic nephropathy and acute kidney injury. Previous studies have reported that mitochondrial transplantation provided surprising results in myocardial and liver ischemia, as well as in Parkinson's disease. We aimed to investigate the beneficial effects of isolated mitochondria transplantation from mesenchymal stem cells (MSCs) in vivo, to mitigate renal damage that arises from doxorubicin-mediated nephrotoxicity and its action mechanism. In this study, a kidney model of doxorubicin-mediated nephrotoxicity was used and isolated mitochondria from MSCs were transferred to the renal cortex of rats. The findings showed that the rate of isolated mitochondria from MSCs maintains sufficient membrane integrity, and was associated with a beneficial renal therapeutic effect. Following doxorubicin-mediated renal injury, isolated mitochondria or vehicle infused into the renal cortex and rats were monitored for five days. This study found that mitochondrial transplantation decreased cellular oxidative stress and promoted regeneration of tubular cells after renal injury (P < .001, P = .009). Moreover, mitochondrial transplantation reduced protein accumulation of tubular cells and reversed renal deficits (P = .01, P < .001). Mitochondrial transplantation increased Bcl-2 levels, and caspase-3 levels decreased in injured renal cells (P < .015, P < .001). Our results provide a direct link between mitochondria dysfunction and doxorubicin-mediated nephrotoxicity and suggest a therapeutic effect of transferring isolated mitochondria obtained from MSCs against renal injury. To our knowledge, this study is the first study in the literature that showed good therapeutic effects of mitochondrial transplantation in a nephrotoxicity model, which is under-researched.


Assuntos
Doxorrubicina/efeitos adversos , Nefropatias , Células-Tronco Mesenquimais/metabolismo , Mitocôndrias , Animais , Doxorrubicina/farmacologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/terapia , Masculino , Células-Tronco Mesenquimais/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/transplante , Ratos , Ratos Sprague-Dawley
5.
Int J Ophthalmol ; 9(9): 1265-70, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27672589

RESUMO

AIM: To examine changes in retinal vasculature after treatment with different oxygen concentrations from common retinopathy of prematurity (ROP) models and to determine a novel and practical ROP model. METHODS: A sample of 14 newborn Sprague-Dawley rats was used. The study group (n=7) was exposed to 95% oxygen for 4h per day followed by normoxic laboratory conditions for 20h. This cycle was repeated for 14d. The control group (n=7) was subjected to normobaric normoxic conditions. On postnatal day 14 (P14), the two groups were placed in room air for 7d. On P21, the two groups were examined using indirect ophthalmoscopy. All eyes were enucleated for immunofluorescence (IF) staining of the vasculature of retinas and analysis of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1α), placental growth factor (PLGF) in vitreous humor, and then the rats were sacrificed by decapitation. All procedures were repeated using another litter of 14 pups. RESULTS: In the study group and under normobaric hyperoxic conditions, retinal neovascularization and peripheral avascular retina were determined in 85% of the rats through indirect ophthalmoscopic examination. Also IF staining of retina of the study group showed retarded peripheral vascular growth. The difference between the two groups for VEGF, HIF-1α and PLGF concentrations of vitreous humor was statistically significant (P=0.003, 0.007, 0.027 respectively). CONCLUSION: Fluctuating oxygen concentrations are primarily responsible for retinal neovascularization. Our new ROP model is practical and applicable for all retinal neovascularization studies, considering the laboratory procedures.

6.
Turk J Med Sci ; 45(1): 105-11, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25790538

RESUMO

BACKGROUND/AIM: Since blood bags have the ability for diffusion of gases, we investigated whether hyperbaric oxygen (HBO) exposure affects several vital parameters of stored blood. MATERIALS AND METHODS: Bloods obtained from the same persons were used as both control and HBO groups and stored in pediatric bags with citrate-phosphate-dextrose solution. HBO administration was performed at 2.5 atm for 90 min, started 1 day after blood collection and repeated every 2 days for a total of 10 times. The study was terminated on the 21st day. Complete blood count, glucose, pH, and osmotic fragility values were measured every week. RESULTS: Glucose and pH levels decreased in stored blood. In the HBO-exposed group, these decreases were less than in the control. In addition, mean corpuscular and platelet volumes tended to increase during storing process, but with HBO, these indexes remained lower, near physiologic levels. Another interesting finding of the study was the relative stable osmotic fragility ratio in the HBO group compared to the control blood. CONCLUSION: HBO exposure has positive effects on pH, stability of erythrocytes, and energy source (glucose) of the medium. Thus, we concluded that HBO may be a useful application for life and quality of stored blood.


Assuntos
Preservação de Sangue/métodos , Eritrócitos , Oxigênio , Adulto , Glicemia , Transfusão de Sangue Autóloga , Citratos , Índices de Eritrócitos , Eritrócitos/química , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/fisiologia , Glucose , Humanos , Masculino , Oxigênio/metabolismo , Oxigênio/farmacologia
7.
Int J Surg ; 12(12): 1434-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25448667

RESUMO

BACKGROUND: The effect of the timing of the second laparotomy on wound healing is not clear. In an experimental study in rats, we aimed to investigate the effect of timing on wound healing after reoperations on the same surgical site. MATERIAL AND METHODS: Forty-eight rats were divided into four groups. The control group (GC) didn't have another laparotomy whereas the relaparotomies on the same surgical site were performed either on the 3rd, 15th or the 30th postoperative days in the three study groups (G3, G15, G30 respectively). The midline tension pressure, collagen types I, III and, histological analysis were performed from the specimens in order to assess the wound healing and strength. RESULTS: The tensile strength was the highest in GC and decreased gradually in G3, G15 and G30, the difference between the groups did not reach statistical significance. Higher collagen levels, increased fibrosis, and large defects were observed in relaparotomy groups than CG. The musculoaponeurotic gap was shortest in GC when compared to other three relaparotomy groups (P < 0.001) and, it was the longest in G30 (P = 0.004 between G3 and G30). CONCLUSIONS: Although non-statistically significant the gradual decrease in the tensile strength and the statistically significant increase in the musculoaponeurotic gap with time point out the importance of the timing of relaparotomy in the healing process. Early relaparotomies do not disrupt the healing process as much as relaparotomy performed later.


Assuntos
Laparotomia , Resistência à Tração/fisiologia , Cicatrização/fisiologia , Animais , Colágeno/análise , Modelos Animais de Doenças , Ratos , Reoperação , Fatores de Tempo
8.
PLoS One ; 9(11): e112239, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25379771

RESUMO

PAKs are serine/threonine kinases that regulate cytoskeletal dynamics and cell migration. PAK1 is activated by binding to the small EF hand protein, CIB1, or to the Rho GTPases Rac1 or Cdc42. The role of PAK1 in angiogenesis was established based only on in vitro studies and its role in angiogenesis in vivo has never been examined. Here we tested the hypothesis that PAK1 is an essential regulator of ischemic neovascularization (arteriogenesis and angiogenesis) and wound healing using a global PAK1 knockout mouse. Neovascularization was assessed using unilateral hindlimb ischemia. We found that plantar perfusion, limb use and appearance were not significantly different between 6-8 week old PAK1-/- and PAK1+/+ mice throughout the 21-day period following hindlimb ischemia; however a slightly delayed healing was observed in 16 week old PAK1-/- mice. In addition, the wound healing rate, as assessed with an ear punch assay, was unchanged in PAK1-/- mice. Surprisingly, however, we observed a notable increase in PAK2 expression and phosphorylation in ischemic gastrocnemius tissue from PAK1-/- but not PAK1+/+ mice. Furthermore, we observed higher levels of activated ERK2, but not AKT, in ischemic and non-ischemic muscle of PAK1-/- mice upon hindlimb ischemic injury. A group I PAK inhibitor, IPA3, significantly inhibited endothelial cell sprouting from aortic rings in both PAK1-/- and PAK1+/+ mice, implying that PAK2 is a potential contributor to this process. Taken together, our data indicate that while PAK1 has the potential to contribute to neovascularization and wound healing, PAK2 may functionally compensate when PAK1 is deficient.


Assuntos
Membro Posterior/irrigação sanguínea , Isquemia/metabolismo , Cicatrização , Quinases Ativadas por p21/metabolismo , Animais , Movimento Celular , Feminino , Deleção de Genes , Membro Posterior/metabolismo , Membro Posterior/patologia , Isquemia/genética , Isquemia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neovascularização Fisiológica , Quinases Ativadas por p21/genética
9.
Otol Neurotol ; 33(9): 1672-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23007643

RESUMO

HYPOTHESIS: To investigate effects of dexamethasone and hyperbaric oxygen therapy (HBOT) on proinflammatory cytokines and hearing levels in the noise-exposed cochlea of rats. BACKGROUND: There is an arising concern about negative effects of early initiation of HBOT on hearing in noise-induced hearing loss. Furthermore, effects of HBOT and dexamethasone on cochlear cytokines are not fully elucidated. METHODS: Twenty-six rats were divided into 3 groups: control, noise, and treatment groups. Five rats served as control group. White noise at 115 dB sound pressure level was applied to the noise group of 4 rats for 10 days. This group was assigned to a positive control group as it was equivalent to treatment groups. The treatment group of 17 rats underwent the same noise exposure, and then, they were divided into 3 groups based on treatment protocol: 5 and 6 rats received HBOT at the third hour and 24th hour after the noise, respectively, and 6 rats received dexamethasone. Auditory brain stem response threshold was measured in all groups before being assigned to the groups, after the noise exposure and right before being killed. Cytokine levels at the cochlear soft tissues were measured using enzyme-linked immunoassay. RESULTS: Final thresholds (10 dB and 5 dB nHL-normal hearing level) of HBOT-24th hour and dexamethasone groups were significantly better than that of untreated noise group (22.5 dB nHL) (p < 0.05). There was no significant difference between HBOT-24th hour group (10 dB nHL) and dexamethasone group (5 dB nHL) (p > 0.05). IL-6 and IL-1ß of HBOT-third hour group (2.30 ng/mg and 185.43 pg/mg) were significantly higher than those of the noise group (0.91 ng/mg and 131.40 pg/mg), dexamethasone group (1.19 ng/mg and 112.29 pg/mg) and HBOT-24th hour group (1.34 ng/mg and 106.69 pg/mg) (p < 0.05). There was no significant difference in IL-6 and IL-1ß of HBOT-24th hour group, dexamethasone group, noise group, and control group (p > 0.05). There was no significant difference in TNF-α of the 3 treatment groups, noise group, and control group (p > 0.05). CONCLUSION: The results showed that the most effective method in the treatment of noise-induced hearing loss was early initiation of dexamethasone therapy. There could be negative effects of HBOT on hearing if it is commenced early after the noise (first 3 h). HBOT treatment, which was started at the 24th hour, was found to be an effective method.


Assuntos
Anti-Inflamatórios/farmacologia , Cóclea/metabolismo , Citocinas/metabolismo , Dexametasona/farmacologia , Perda Auditiva Provocada por Ruído/metabolismo , Oxigenoterapia Hiperbárica , Estimulação Acústica , Animais , Limiar Auditivo , Cóclea/anatomia & histologia , Cóclea/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Ruído/efeitos adversos , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
10.
ScientificWorldJournal ; 2012: 849183, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22454610

RESUMO

Hyperbaric oxygen (HBO(2)) exposure affects both oxidative and antioxidant systems. This effect is positively correlated with the exposure time and duration of the treatment. The present study aims enlightening the relation of HBO(2) with oxidative/antioxidant systems when administered in a prolonged and repetitive manner in brain tissues of rats. Sixty rats were divided into 6 study (n = 8 for each) and 1 control (n = 12) group. Rats in the study groups were daily exposed 90-min HBO(2) sessions at 2.8 ATA for 5, 10, 15, 20, 30 and 40 days. One day after the last session, animals were sacrificed; their whole brain tissue was harvested and dissected into three different regions as the outer grey matter (cortex), the inner white matter and cerebellum. Levels of lipid peroxidation and protein oxidation and activities of superoxide dismutase and glutathione peroxidase were measured in these tissues. Malondialdehyde, carbonylated protein and glutathione peroxidase levels were found to be insignificantly increased at different time-points in the cerebral cortex, inner white matter and cerebellum, respectively. These comparable results provide evidence for the safety of HBO treatments and/or successful adaptive mechanisms at least in the brain tissue of rats, even when administered for longer periods.


Assuntos
Encéfalo/metabolismo , Oxigenoterapia Hiperbárica , Estresse Oxidativo , Animais , Antioxidantes/metabolismo , Encéfalo/enzimologia , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
11.
Environ Toxicol Pharmacol ; 34(1): 81-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22459800

RESUMO

OBJECTIVES: Acetaminophen (APAP) overdose may cause acute liver injury. Ozone therapy (OT) is shown to reduce inflammation and necrosis in several entities. Thus, we have designed this study to evaluate the efficacy of OT in a rat model of APAP-induced liver injury. METHODS: Twenty-seven Sprague-Dawley rats were divided into three groups: sham, APAP and APAP+OT groups. In the APAP and the APAP+OT groups, liver injury was induced by oral administration of 1 g/kg APAP. The APAP+OT group received a single dose ozone/oxygen mixture (0.7 mg/kg) intraperitoneally 1h after APAP administration. All animals were killed at 24 hour after APAP administration. Blood samples and liver tissues were harvested to determine liver injury and oxidative stress parameters. Liver tissues and blood samples were obtained for biochemical and histopathological analyses. RESULTS: APAP administration caused necrosis in the liver after 24h. The degrees of liver necrosis of the APAP group were higher than the other groups (in both p<0.05, respectively). In the APAP+OT group, liver antioxidant enzymes activities were significantly higher than the APAP group (p<0.05), but were lower than the sham group (p<0.05). In the sham group, serum neopterin, a marker of cell-mediated immunity, concentrations (4.8±1.2 nmol/L) were lower than the APAP (14.7±1.4 nmol/L) and APAP+OT groups (7.5±2.4 nmol/L) (in both p<0.05, respectively). CONCLUSION: Our results showed that OT prevented liver necrosis in rats and reduced neopterin levels. These findings suggest that the use of OT as an adjuvant therapy which might improve the outcome in APAP induced liver injury.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Ozônio/uso terapêutico , Substâncias Protetoras/uso terapêutico , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Glutationa Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Necrose/induzido quimicamente , Necrose/tratamento farmacológico , Necrose/metabolismo , Necrose/patologia , Neopterina/sangue , Nitratos/sangue , Nitritos/sangue , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
12.
Free Radic Res ; 45(11-12): 1267-78, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21955297

RESUMO

Hyperbaric oxygen (HBO) treatment is based on the principle of having the patient breath 100% oxygen in an environment above atmospheric pressure. Ozone (O(3)) is a colourless gas with a specific odour and consists of three oxygen atoms. The classical scientific understanding is that the world has become a place suitable for life for aerobic organisms with the increasing oxygen in the atmosphere billions of years ago. The formation of ozone after oxygen has then protected aerobic creatures from harmful rays. We now use these two gases for treatment purposes. It is noteworthy that the oxygen and ozone molecules that are formed by the same atom in different numbers are used for similar medical indications. We will try to emphasize the similarities and differences of HBO and medical ozone applications in this article.


Assuntos
Oxigenoterapia Hiperbárica , Estresse Oxidativo , Oxigênio/uso terapêutico , Ozônio/uso terapêutico , Antioxidantes/química , Atmosfera/química , Pressão Atmosférica , Heme Oxigenase-1/química , Heme Oxigenase-1/metabolismo , Humanos , Oxigênio/metabolismo , Ozônio/química
13.
Scand J Clin Lab Invest ; 71(6): 473-80, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21923232

RESUMO

INTRODUCTION: Not only bacterial characteristics but also oxidative/nitrosative stress could play a significant role in renal parenchymal inflammatory processes in acute pyelonephritis (APN). This study was conducted to evaluate the effect of ozone therapy (OT), as an immunomodulator and antioxidant, on the renal function, morphology and biochemical parameters of oxidative stress in an experimental model of APN in rats. MATERIALS AND METHODS: Forty rats were divided equally into five groups as control, APN, APN + Antibiotic, APN + OT, and APN + Antibiotic + OT. APN was induced by 0.1 ml of freshly prepared Escherichia coli (ATCC 25922) solution containing 10(10) colony-forming unit/ml into the kidney. A control group was administered 0.1 ml of 0.9 % NaCl solution. Treatment was begun 72 h after bacterial inoculation. Control and APN groups were given 0.9% NaCl solution, APN + Antibiotic and APN + OT were given either antibiotic (ciprofloxacine 150 mg/kg intramuscular/twice daily) or OT. APN + Antibiotic + OT group was given both antibiotic and OT for five consecutive days. At the end of the seventh day, animals were killed via decapitation and trunk blood was collected. Both kidneys were harvested and one half of each kidney were immediately stored for antioxidant enzyme activity, tissue lipid peroxidation and protein carbonyl content. The remainder was fixed for histopathologic examination. RESULTS: E. coli-induced APN increased the renal glomerular and tubular dysfunction, oxidative stress parameters and antioxidant enzyme activities. Either antibiotherapy or OT markedly ameliorated renal dysfunction, the antioxidant status of the kidneys and histopathological injuries subjected to E. coli-induced APN. Interestingly, the combination of antibiotherapy and OT was much more effective than either of the treatment modalities alone. CONCLUSION: The combination of antibiotherapy and OT markedly ameliorated renal dysfunction and improved antioxidant status and histopathologic modalities in rats subjected to E. coli-induced APN than either antibiotherapy or OT treatment alone. Therefore, OT may be considered as an adjuvant therapy to classical antibiotherapy to prevent renal inflammation and fibrosis in APN.


Assuntos
Rim/patologia , Ozônio/uso terapêutico , Pielonefrite/prevenção & controle , Doença Aguda , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Aspartato Aminotransferases/sangue , Calcitonina/sangue , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Creatina/sangue , Modelos Animais de Doenças , Quimioterapia Combinada , Infecções por Escherichia coli/complicações , Fibrose , Glutationa Peroxidase/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , L-Lactato Desidrogenase/sangue , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Neopterina/sangue , Estresse Oxidativo , Ozônio/farmacologia , Precursores de Proteínas/sangue , Pielonefrite/sangue , Pielonefrite/microbiologia , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Ureia/sangue
14.
Turk J Gastroenterol ; 22(2): 190-4, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21796557

RESUMO

BACKGROUND/AIMS: Peritoneal adhesions, which occur most frequently after abdominal and pelvic operations, may lead to serious complications such as small intestine obstruction. In various studies, it has been shown that oxidative stress may play a role in the development of peritoneal adhesions, and studies carried out with antioxidants reported positive results. In the present study, the probable preventive role of alpha-lipoic acid, a strong antioxidant, in the development of peritoneal adhesions was investigated. METHODS: Sixteen Sprague-Dawley male rats weighing 200-250 grams were employed. Under ketamine+xylazine anesthesia, on the antimesenteric aspect of the cecum, an adhesion model was formed with an incision, and half of the experimental animals were administered a daily single dose 100 mg/kg alpha-lipoic acid through orogastric gavage, and the other half formed the control group. Abdomens were opened 15 days later, and after adhesions were scored macroscopically, tissue samples were taken for evaluation of biochemical parameters. RESULTS: In both adhesion scoring methods, a statistically significant decrease was found in the alpha-lipoic acid group compared to the control group (p<0.05). The decrease in adhesions was also confirmed by the significantly lower hydroxyproline levels in the alpha-lipoic acid group (p<0.05). In addition, alpha-lipoic acid decreased malondialdehyde levels in the adhesion region and prevented the increase in superoxide dismutase and glutathione peroxidase activities significantly (p<0.05). CONCLUSIONS: It can be concluded from the findings of our study that alpha-lipoic acid decreased the development of adhesions in a peritoneal adhesion model and increased the quality of healing. These findings suggest that alpha-lipoic acid, already long used in various indications, may be tried clinically in patients about to undergo abdominal operations.


Assuntos
Antioxidantes/farmacologia , Peritônio/metabolismo , Ácido Tióctico/farmacologia , Aderências Teciduais/prevenção & controle , Animais , Modelos Animais de Doenças , Hidroxiprolina/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peritônio/patologia , Ratos , Ratos Sprague-Dawley , Aderências Teciduais/metabolismo , Aderências Teciduais/patologia
15.
Scand J Clin Lab Invest ; 71(5): 370-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21463160

RESUMO

OBJECTIVE: Previously, it was shown that ozone and S-methylthiourea (SMT) treatments had ameliorative effects on experimental models of acute necrotizing pancreatitis (ANP). It is possible that the combination of ozone and SMT may be more effective than either therapy. Therefore, we investigated the efficacy of combination therapy with ozone and SMT in an experimental rat model of ANP. MATERIAL AND METHODS: Sprague-Dawley rats were divided into five experimental groups. Groups were designed as Sham-operated, ANP, ANP + Ozone, ANP + SMT and ANP + Ozone + SMT. A model of ANP was induced by injection of sodium taurocholate into the common biliopancreatic duct. Four days after induction, blood and tissue samples were obtained for biochemical, microbiological and histopathological analysis. RESULTS: Survival rates, serum amylase, lipase and neopterin levels, tissue oxidative stress parameters, bacterial translocation and tissue injury scores were better in the ozone and SMT groups than in the ANP group. There was no bacterial translocation in the ozone-treated groups. Tissue injury scores in the ozone group were better compared to all ANP induced groups. Ozone and SMT treatment in combination did not have better biochemical, microbiological and histological data compared to ozone or SMT treatments separately in experimental ANP. CONCLUSIONS: The combination of ozone and SMT did not provide any therapeutic advantage in ANP possibly because SMT inhibited nitric oxide synthesis which was needed for ozone action.


Assuntos
Isotiurônio/análogos & derivados , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Ozônio/uso terapêutico , Pancreatite Necrosante Aguda/tratamento farmacológico , Animais , Proteínas Sanguíneas/metabolismo , Escherichia coli , Isotiurônio/farmacologia , Peroxidação de Lipídeos , Masculino , Estresse Oxidativo , Pâncreas/microbiologia , Pâncreas/patologia , Pancreatite Necrosante Aguda/induzido quimicamente , Pancreatite Necrosante Aguda/metabolismo , Proteus mirabilis , Ratos , Ratos Sprague-Dawley , Ácido Taurocólico
16.
Inhal Toxicol ; 23(3): 166-72, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21391785

RESUMO

CONTEXT: Despite its known benefits, hyperbaric oxygen (HBO) is also reported to enhance the production of reactive oxygen species and can cause oxidative stress in several tissues. Previous studies had shown that HBO-induced oxidative stress is directly proportional to both its exposure pressure and duration. Nevertheless, these studies were usually performed with single-session HBO exposure but its clinical use commonly depends on long-term exposure periods. OBJECTIVE: To clarify the oxidative effect of long-term repetitive HBO in the lung tissue of rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into six study groups exposed to consecutive HBO sessions (2.8 atm/90 min) for 5, 10, 15, 20, 30, and 40 days. Animals were sacrificed 24 h after the last HBO session. An additional control group was set to obtain normal data. Lung malondialdehyde (MDA) and carbonylated protein (PCC) levels were determined as measures of oxidative stress along with the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase. RESULTS: None of the measured parameters showed any changes among the groups exposed to 5-15 HBO sessions. However, MDA, PCC, and SOD were found to be significantly increased in the 20 to 40 session groups. DISCUSSION AND CONCLUSION: These results indicate that repetitive treatment with HBO may cause oxidative stress in critical tissues including the lung. Although HBO-mediated free radicals are accepted to be responsible for the benefits of this therapeutic modality, especially in cases with prolonged exposure, possible injurious effects of supranormal values of bio-oxidative products need to be considered.


Assuntos
Oxigenoterapia Hiperbárica/efeitos adversos , Pulmão/metabolismo , Estresse Oxidativo , Animais , Biomarcadores/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos , Masculino , Malondialdeído/metabolismo , Carbonilação Proteica , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fatores de Tempo
17.
Food Chem Toxicol ; 49(6): 1353-60, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21419821

RESUMO

The fatty acids of Agaricus essettei, Agaricus bitorquis and Agaricus bisporus were investigated by using GC and GC-MS. The dominant fatty acids were found to be linoleic (61.82-67.29%) and palmitic (12.67-14.71%) acids among the 13 fatty acids detected in the oils. Total unsaturation for the oils was calculated as 77.50%, 77.44%, and 79.72%, respectively. In vitro antioxidant, anticholinesterase and antimicrobial activities were also studied. The ethyl acetate extract of Agaricus bitorquis showed the highest activity in ß-carotene-linoleic acid, DPPH(·) and ABTS(·)(+) assays, while the hexane extract of Agaricus bisporus exhibited the best metal chelating activity. The ethyl acetate and hexane extract of Agaricus bitorquis and the hexane extract of Agaricus essettei showed meaningful butyrylcholinesterase activity being close to that of galantamine. The extracts were found to be effective on Gram (+) bacteria, especially against Micrococcus luteus, Micrococcus flavus, Bacillus subtilis and Bacillus cereus. In conclusion, Agaricus bitorquis and Agaricus essettei demonstrated higher iron content, and better antioxidant, anticholinesterase and antimicrobial activities than those of Agaricus bisporus commonly consumed mushroom. Hence, Agaricus species, particularly Agaricus bitorquis might be useful as antioxidant agents and moderate anticholinesterase agents, and their extracts will probably be used for development of dietary foods, food products and additives.


Assuntos
Agaricus/química , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Extratos Vegetais/farmacologia , Anti-Infecciosos/química , Antioxidantes/análise , Antioxidantes/química , Bactérias/efeitos dos fármacos , Benzotiazóis/química , Compostos de Bifenilo/química , Inibidores da Colinesterase/química , Ácidos Graxos/análise , Sequestradores de Radicais Livres/química , Cromatografia Gasosa-Espectrometria de Massas , Indicadores e Reagentes/química , Compostos de Ferro/análise , Testes de Sensibilidade Microbiana , Oxirredução , Picratos/química , Extratos Vegetais/química , Ácidos Sulfônicos/química , beta Caroteno/química
18.
Clin Appl Thromb Hemost ; 17(2): 202-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20460337

RESUMO

OBJECTIVES: The lack of response of platelets against epinephrine has been discovered with a frequency of 14% to 40% in previous studies. There are studies that have demonstrated the effect of aspirin on platelets may resemble the lack of response to epinephrine. In this study, the extent of the effects of aspirin treatment on aggregation and secretion in healthy males with a lack of response to epinephrine and the frequency of aspirin resistance were investigated. METHODS: Blood samples were collected at the beginning and at the end of a 10-day aspirin usage in 52 healthy males. Epinephrine, adenosine diphosphate (ADP), collagen, arachidonic acid (AA) and thrombin aggregations, and adenosine triphosphate (ATP) secretion were studied. Participants were assigned to nonresponder (<20%), semiresponder (20%-60%), and responder (>60%) groups, depending on their maximum aggregation responses to epinephrine. Participants who displayed an aggregation to AA at the end of the aspirin treatment were accepted to be aspirin resistant. RESULTS: Of the 52 participants, 4 were found to be nonresponders and 3 of 52 of the participants were found to be semiresponders. Although the lack of response to epinephrine and aspirin treatment displayed similarities in aggregations using epinephrine, ADP, collagen, and thrombin, they differed in aggregations using AA and for ATP secretion. The ratio of aspirin resistance was determined to be 4:52. CONCLUSIONS: The observation of AA aggregation in the participants with a lack of response to epinephrine demonstrates that epinephrine nonresponse cannot substitute aspirin treatment. The fact that aspirin resistance is observed in healthy males supports the view that aspirin resistance exists even before the first usage.


Assuntos
Agonistas alfa-Adrenérgicos/administração & dosagem , Aspirina/administração & dosagem , Resistência a Medicamentos , Epinefrina/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Adulto , Humanos , Masculino , Agregação Plaquetária/efeitos dos fármacos , Fatores de Tempo
19.
J Pineal Res ; 50(1): 89-96, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21062350

RESUMO

Doxorubicin (DOX) and Trastuzumab (TRAST) are effective agents for the treatment of many neoplastic diseases. Cardiotoxicity is a major side effect of these drugs and limit their use. In this study, the possible protective effects of melatonin (MEL), mercaptoethylguanidine (MEG), or N-(3-(aminomethyl) benzyl) acetamidine (1400W) against the cardiotoxicity of DOX and TRAST were tested. Male Sprague-Dawley rats received an injection of DOX (20 mg/kg) alone or in combination with TRAST (10 mg/kg) to induce cardiotoxicity; daily treatments with MEL (10 mg/kg × 2), MEG (10 mg/kg × 2), or 1400W (10 mg/kg × 2) were begun 36 hr before and continued for 72 hr after DOX and TRAST administration. Oxidant/antioxidant indices of the cardiac tissue, namely, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as serum levels of creatine phosphokinase (CK-MB) were measured. Additionally, the injury scores were evaluated histopathologically. Malondialdehyde levels were significantly higher, while SOD and GSH-Px activities were significantly reduced in rats with DOX- or DOX+TRAST-induced cardiotoxicity compared to normal values. All three treatment agents significantly reversed oxidative stress markers. Serum CK-MB levels were significantly increased after treatment with DOX and DOX+TRAST; these changes were also reversed by each of the treatments and resulted in near normal levels. Both the DOX- and DOX+TRAST-treated rats presented similar histopathologic injuries; in the animals treated with the protective agents, histologic protection of the cardiac tissue was apparent. These results suggested that MEL, MEG, as well as 1400 W are effective in preventing DOX- or DOX+TRAST-induced cardiotoxicity.


Assuntos
Amidinas/farmacologia , Anticorpos Monoclonais/farmacologia , Benzilaminas/farmacologia , Doxorrubicina/farmacologia , Guanidinas/farmacologia , Melatonina/farmacologia , Animais , Anticorpos Monoclonais Humanizados , Creatina Quinase/metabolismo , Glutationa Peroxidase/metabolismo , Coração/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Trastuzumab
20.
Exp Biol Med (Maywood) ; 235(9): 1126-33, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20705631

RESUMO

Various studies have been performed to find out novel treatment strategies for acute necrotizing pancreatitis (ANP). Inhibition of poly(ADP-ribose) polymerase (PARP) is shown to reduce inflammation in several pathological conditions. We aimed to evaluate the efficacy of benzamide, a PARP inhibitor, in an experimental model of ANP. Thirty Sprague-Dawley rats were divided into three groups: sham-operated, ANP and ANP + benzamide groups. All groups except the sham-operated group were subjected to the ANP procedure, induced by infusing of 1 mL/kg of 3% sodium taurocholate into the common biliopancreatic duct. The ANP + benzamide group received 100 mg/kg/day benzamide intraperitoneally for a total of three days after induction of pancreatitis. The surviving animals were killed at the fourth day and the pancreas was harvested for biochemical, microbiological and histological analysis. Blood samples were also obtained from the animals. In the ANP group, a significant increase was observed in concentrations of serum amylase and neopterin and tissue oxidative stress indices (malondialdehyde, superoxide dismutase and glutathione peroxidase). Almost all of these changes were found to be reversed to near their normal values in the ANP + benzamide group. Histological injury scores were significantly higher in the ANP group than in the sham group (P < 0.05, ANP versus sham), and were significantly lower in the ANP + benzamide group than in the ANP group (P < 0.05, ANP + benzamide versus ANP). Evaluation of bacterial translocation identified significantly fewer infected sites in the ANP + benzamide group than in the ANP animals (P < 0.01). We observed that inhibition of PARP with benzamide reduced the severity, the mortality, the bacterial translocation rates and the neopterin concentrations in an experimental ANP model in rats. These findings suggest that it may be possible to improve the outcome of ANP by using PARP inhibitors.


Assuntos
Translocação Bacteriana/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pancreatite Necrosante Aguda/microbiologia , Adenosina Difosfato Ribose/metabolismo , Amilases/efeitos adversos , Amilases/sangue , Amilases/metabolismo , Animais , Benzamidas , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Masculino , Malondialdeído/efeitos adversos , Malondialdeído/metabolismo , Neopterina/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite/metabolismo , Pancreatite Necrosante Aguda/induzido quimicamente , Pancreatite Necrosante Aguda/patologia , Poli Adenosina Difosfato Ribose/efeitos adversos , Poli Adenosina Difosfato Ribose/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/efeitos adversos , Superóxido Dismutase/metabolismo , Ácido Taurocólico/efeitos adversos , Ácido Taurocólico/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...