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BACKGROUND: Alopecia areata (AA) is a disease characterized by the hair loss sharply limited in any part of the body, especially on the scalp, in circular or oval areas. The purpose of this study is to search the serum paraoxonase 1 (PON1), arylesterase and oxidative status with serum prolidase activities in people with AA. METHODS: The study included 60 AA and 50 healthy control subjects. In both groups, serum PON1, prolidase, arylesterase activities, total oxidative status (TOS) and total antioxidant capacity (TAS) levels and oxidative stress index (OSI) were calculated. RESULTS: TOS, OSI levels and prolidase activity in patients with AA were found to be significantly higher compared to the control group (p = 0.02, p = 0.004, p < 0.001, respectively), whereas PON1 and arylesterase activities were significantly lower (p < 0.001, p = 0.005, respectively). There was no difference in serum TAS levels between the two groups. CONCLUSION: This comprehensive work shows that the role of oxidative stress is very important in the pathogenesis of AA. In this study, we believe that we clarified the pathogenesis of oxidative stress for AA patients by investigating the TAS, TOS, OSI levels, PON1, arylesterase and prolidase enzyme activity parameters.
Assuntos
Alopecia em Áreas/sangue , Arildialquilfosfatase/sangue , Hidrolases de Éster Carboxílico/sangue , Dipeptidases/sangue , Adulto , Feminino , Humanos , Masculino , Estresse Oxidativo , Adulto JovemRESUMO
Amikacin (AK) is frequently used on the treatment of Gram-negative infections on neonates, but its usage is restricted because of nephrotoxicity. In this study, on neonatal rats, we aimed to investigate the effects of erythropoietin and vitamin E on AK induced nephrotoxicity. A total of 35 newborn Wistar Albino rats were divided into four groups: (1) injected with saline (serum physiological was administered to placebo controls), (2) injected with AK (1200 mg/kg), (3) injected with AK + vitamin E (150 mg/kg), (4) injected with AK + erythropoietin (EPO) (300 IU/kg/day). In renal tissue, AK levels were significantly high in all groups except the control. Tissue malondialdehyde (MDA) and nitric oxide (NO) levels were statistically higher in AK -treated group than the control. MDA and NO levels were significantly decreased with the administration of vitamin E and EPO. Glutathione peroxidase (GPX) levels were statistically low in AK group compared with the controls. The levels of GPX, in vitamin E group, were increased significantly. However, superoxide dismutase and catalase levels were not significantly different in none of the groups. Insulin-like growth factor-1 values in AK, EPO and vitamin E groups were significantly higher than the control group. Histomorphological changes such as tubular epithelial necrosis were seen in AK treated group. Histopathological improvements observed with EPO and vitamin E administration. AK nephrotoxicity is related to oxidative stress and is supported with biochemical and histopathological findings. Vitamin E and EPO, as antioxidants, can be useful renoprotective agents for ameliorating AK induced nephrotoxicity in neonates.
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Amicacina/efeitos adversos , Eritropoetina/farmacologia , Nefropatias , Estresse Oxidativo/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Animais Recém-Nascidos , Antibacterianos/efeitos adversos , Antioxidantes/farmacologia , Modelos Animais de Doenças , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico , Nefropatias/metabolismo , Nefropatias/prevenção & controle , Testes de Função Renal/métodos , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
AIMS: Acute myocardial infarction is a serious acute cardiac disorder and heart disease is still a major public health problem in adults. We investigated the effects of embelin (EMB) and carnosic acid (CA) in animals with isoproterenol (ISO)-induced myocardial injury. MAIN METHODS: Adult male Wistar-Albino rats were divided into four groups: control, ISO, ISO with EMB, and ISO with CA. Before myocardial injury was induced, drugs were administered by oral gavage. Myocardial injury was induced by subcutaneous injection of ISO hydrochloride for 2 consecutive days. Serum cardiac troponin I (cTnI), ischemia modified albumin (IMA), heart fatty acid binding protein (HFABP) levels and paraoxonase-1 (PON-1) activity, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), tumor necrosis factor-α (TNF-α) levels, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of nuclear factor-kappa B (NF-κB), P38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2) were analyzed. In addition, cardiac tissues were evaluated histopathologically and immunohistochemically. KEY FINDINGS: All tested compounds reduced myocardial damage, apoptosis, cTnI, IMA, HFABP, TOS, and TNF-α levels, NF-κB, p38 MAPK, and phosphorylated c-Jun N-terminal protein kinase (pJNK 1/2) expressions. All tested compounds increased SOD activity, GSH-Px activity, TAS levels, TT levels, phosphorylated extracellular signal-regulated kinase (pERK 1/2), and Nrf2 expressions. SIGNIFICANCE: Our results suggest that EMB and CA pretreatment could reduce myocardial injury via antiinflammatory, antioxidant, and antiapoptotic effects.
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Abietanos/farmacologia , Apoptose/efeitos dos fármacos , Benzoquinonas/farmacologia , Cardiotônicos/farmacologia , Infarto do Miocárdio/prevenção & controle , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Isoproterenol/toxicidade , Masculino , Infarto do Miocárdio/fisiopatologia , RNA Mensageiro/metabolismo , Ratos , Ratos WistarRESUMO
The aim of the present study was to assess the protective effect of silibinin against methotrexate (MTX)-induced pulmonary toxicity. Rats were divided into four groups (MTX, MTX + silibinin, silibinin and control. MTX was injected intraperitoneally (i.p) into female Wistar rats (10 mg/kg/day for 3 days), which resulted in significant increases in the serum levels of alanine aminotransferase, aspartate aminotransferase and oxidant enzymes, including nitric oxide and myeloperoxidase. Furthermore, significant reductions were detected in the serum activity levels of the antioxidative enzymes, glutathione peroxidase and superoxide dismutase, when compared with the control group. However, administration of silibinin (100 mg/kg/day for 10 days, i.p.) was shown to ameliorate the MTX-induced pulmonary toxicity, as indicated by the normalization of the oxidative stress parameters. Furthermore, silibinin treatment was demonstrated to reduce the histopathological changes associated with MTX. In conclusion, silibinin exhibited protective effects against MTX-induced pulmonary toxicity, which may be attributed to its antioxidant activity.
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INTRODUCTION: Total 25-hydroxyvitamin D [25(OH)D] is the most reliable indicator of vitamin D status. In this study, we compared two automated immunoassay methods, the Abbott Architect 25-OH Vitamin D assay and the Roche Cobas Vitamin D total assay, with the liquid chromatography-tandem mass spectrometry (LC-MS/MS). MATERIALS AND METHODS: One hundred venous blood samples were randomly selected from routine vitamin D tests. Two of the serum aliquots were analyzed at the Abbott Architect i2000 and the Roche Cobas 6000's module e601 in our laboratory within the same day. The other serum aliquots were analyzed at the LC-MS/MS in different laboratory. Passing-Bablok regression analysis and Bland-Altman plot were used to compare methods. Inter-rater agreement was analyzed using kappa (κ) analysis. RESULTS: The Roche assay showed acceptable agreement with the LC-MS/MS based on Passing-Bablok analysis (intercept: -5.23 nmol/L, 95% CI: -8.73 to 0.19; slope: 0.97, 95% CI: 0.77 to 1.15). The Abbott assay showed proportional (slope: 0.77, 95% CI: 0.67 to 0.85) and constant differences (intercept: 17.08 nmol/L; 95% CI: 12.98 to 21.39). A mean bias of 15.1% was observed for the Abbott and a mean bias of -14.1% was observed for the Roche based on the Bland-Altman plots. We found strong to nearly perfect agreement in vitamin D status between the immunoassays and LC-MS/MS. (κ: 0.83 for Abbott, κ: 0.93 for Roche) using kappa analysis. CONCLUSION: Both immunoassays demonstrated acceptable performance, but the Roche Cobas assay demonstrated better performance than the Abbott Architect in the studied samples.
Assuntos
Imunoensaio/instrumentação , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Artefatos , Cromatografia Líquida/métodos , Feminino , Humanos , Imunoensaio/métodos , Masculino , Variações Dependentes do Observador , Ligação Proteica , Distribuição Aleatória , Reprodutibilidade dos Testes , Estudos de Amostragem , Espectrometria de Massas em Tandem/métodos , Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Proteína de Ligação a Vitamina D/químicaRESUMO
AIM: To determine whether there is a correlation between cardiac markers and peri-operative myocardial injury (PMI) and apoptosis in coronary artery bypass graft (CABG) surgery and to compare the efficacy of cardiac markers to detect PMI. METHODS: The study population consisted of 37 patients (24 male, 13 female, mean age 63.4 ± 8.9 years) undergoing elective CABG. Arterial and coronary sinus blood samples were collected just before aortic cross-clamping (pre-ACC) and after aortic declamping (post-ACC). Creatine kinase-MB isoenzyme (CK-MB) activity, and high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase-MB isoenzyme mass (CK-MB mass) and cardiac troponin I (cTnI) concentrations were measured in blood samples. Myocardial injury and apoptosis were examined in atrial biopsies. RESULTS: CABG caused PMI and apoptosis in all cases. Concentrations and net releases of cardiac markers significantly increased after aortic declamping (p < 0.001 for CK-MB and CK-MB mass, p < 0.01 for cTnI, p < 0.05 for hs-cTnT). A positive correlation was found between apoptotic index (r = 0.611, p < 0.001 for cTnI; r = 0.806, p < 0.001 for hs-cTnT), myocardial injury score (r = 0.544, p < 0.001 for cTnI; r = 0.719, p < 0.001 for hs-cTnT) and cTnI and hs-cTnT values in the post-ACC period. A positive correlation was found between apoptotic index (r = 0.507, p < 0.001), myocardial injury score (r = 0.416, p = 0.010) and net release of hs-cTnT. Furthermore, a positive correlation was found between aortic cross-clamp (ACC) time (r = 0.448, p = 0.007), cardiopulmonary bypass (CPB) time (r = 0.342, p = 0.047) and net release of hs-cTnT. CONCLUSION: Although both cTnI and hs-cTnT may be specific and efficacious markers of myocardial apoptosis and injury occurring during CABG with CPB, hs-cTnT may be a more useful marker than cTnI to detect peri-operative myocardial apoptosis and injury.
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Apoptose , Ponte de Artéria Coronária/efeitos adversos , Traumatismo por Reperfusão Miocárdica/diagnóstico , Miocárdio/metabolismo , Miocárdio/patologia , Troponina T/sangue , Idoso , Biomarcadores/sangue , Biópsia , Ponte Cardiopulmonar/efeitos adversos , Creatina Quinase Forma MB/sangue , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/patologia , Período Perioperatório , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo , Troponina I/sangue , Regulação para CimaRESUMO
Several studies point to an important function of cyclooxygenase (COX) and prostaglandin signaling in models of synaptic plasticity which is associated with N-methyl-D-aspartate receptors (NMDARs). Cyclooxygenase gene is suggested to be an immediate early gene that is tightly regulated in neurons by NMDA dependent synaptic activity. Nonsteroid Antiinflammatory Drugs (NSAIDs) exert their antiinflammatory effect by the inhibion of COX have controversial effects on learning and memory. We administered ibuprofen as a non-selective COX-2 inhibitor and nimesulide as a selective COX-2 inhibitor for 8 weeks for determining the cognitive impact of subchronic administration of NSAIDs to aged rats. Wistar albino rats (16 mo, n = 30) were separated into control (n = 10), ibuprofen (n = 10) and nimesulide (n = 10) treated groups. First we evaluated hippocampus-dependent spatial memory in the radial arm maze (RAM) and than we evaluated the expression of the NMDAR subunits, NR2A and NR2B by western blotting to see if their expressions are effected by subchronic administration with these drugs. Ibuprofen and nimesulide treated rats completed the task in a statistically significant shorter time when compared with control group (p < 0.01), but there was no statistically significant difference between groups about choice accuracy data in RAM. Furthermore, no statistically significant difference was detected for the protein expressions of NR2A and NR2B of the subjects. Oral administration of ibuprofen and nimesulide for 8 weeks showed no impairment but partly improved spatial memory.
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Scopolamine has been used in neuropsychopharmacology as a standard drug that leads to symptoms mimicking cognitive deficits seen during the aging process in healthy humans and animals. Scopolamine is known to be a nonselective muscarinic receptor blocker, but its chronic effect on the expression of certain hippocampal receptors is not clear. The aim of the present study was to determine the effect of chronic scopolamine administration on hippocampal receptor expression and spatial working memory in two different learning tasks, the water maze and the eight-arm radial maze. Male rats (8-12 months) were trained in both tasks. Subsequently, different groups received physiological saline or 0.1, 0.8, or 2 mg/kg scopolamine hydrobromide, respectively, for 15 days. After drug administration, the rats were retested for both tasks, and hippocampal expressions of NR2A, NR2B, nAChRα7, and mAChRM1 receptors were assessed by western blotting analysis. In both tasks, the spatial working memory was decreased dose dependently in all groups compared with the control group. In terms of receptor expressions, 0.8 and 2 mg/kg scopolamine administration significantly decreased NR2A protein expression, which corroborates suggestions of an interaction between cholinergic and glutamatergic receptors in the hippocampus.
Assuntos
Aprendizagem em Labirinto/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Antagonistas Muscarínicos/toxicidade , Escopolamina/toxicidade , Animais , Western Blotting , Relação Dose-Resposta a Droga , Esquema de Medicação , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Masculino , Antagonistas Muscarínicos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptor Muscarínico M1/genética , Receptores de N-Metil-D-Aspartato/genética , Receptores Nicotínicos/genética , Escopolamina/administração & dosagem , Receptor Nicotínico de Acetilcolina alfa7RESUMO
Diazinon (DI) is a widely used pesticide in agriculture, resulting in environmental deleterious effects on neural systems. The current study was performed to investigate the effects of treatment with vitamins E plus C on brain toxicity, which is possibly induced by DI. Twenty-one male rats were divided into three groups (n = 7/group) as follows: (1) control group (C); (2) DI-treated group (DI); (3) DI + vitamins E plus C-treated group (DI + Vit). In order to examine lipid peroxidation and antioxidant status in rats, the level of malondialdehyde (MDA), activities of two free radical scavanging enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) have been studied in brain of rat. The results showed that treatment with DI induced significant (p < 0.05) increases in the level of serum MDA in rat brain. The vitamins E plus C combination reduced lipid peroxidation in rat brain. The activity of SOD level was significantly higher in DI + Vit group, compared to the control group. GSH-Px, SOD and CAT values were not significantly different in the DI group than in control. Oxidative stress contributes to DI-induced brain toxicity. Our results suggested that vitamins E plus C combination may have a protective effect on DI-induced brain toxicity.
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Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Química Encefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Diazinon/toxicidade , Fármacos Neuroprotetores/farmacologia , Vitamina E/farmacologia , Animais , Antioxidantes/metabolismo , Encéfalo/metabolismo , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Estatísticas não Paramétricas , Superóxido Dismutase/metabolismoRESUMO
INTRODUCTION: Accidental ingestion of caustic substances may cause serious problems in children. Approximately 20% of caustic ingestions result in esophageal stricture formation, resulting from excessive collagen synthesis to the extracellular matrix by fibroblasts. Recent studies showed that a single application of 5-fluorouracil (5-FU) is a very effective inhibitor of fibroblast proliferation and differentiation for prolonged periods. Using an experimental model, we investigated the efficacy of single-dose 5-FU on stricture formation after caustic esophageal burn. MATERIALS AND METHODS: Forty Wistar-Albino rats were divided randomly into 4 equal groups: group 1 (sham-operated group), the esophagus was uninjured and untreated; group 2 (control group), the esophagus was injured and left untreated; group 3 (intraperitoneal treatment group), the esophagus was injured and treated immediately after the burn injury with a single intraperitoneal dose (20 mg/kg) of 5-FU; group 4 (local treatment group), the esophagus was injured and treated immediately after the burn injury with a single intraesophageal application of 5-FU at a concentration of 25 mg/mL. Caustic esophageal burn was produced by instilling 10% NaOH in the distal esophagus. The distal esophagi were harvested at 28 days postoperatively. Histologic sections were assessed by measuring the stenosis index (SI) and histopathologic damage score. Hydroxyproline (HP) levels in the tissues were determined biochemically. RESULTS: There were significant reductions in the SI (P < .05), histopathologic damage score (P < .05), and HP level (P < .05) in the intraperitoneal treatment group when compared with the control group. No significant differences in the SI and histopathologic damage score were detected between the control and local treatment groups (P > .05), whereas significant reduction in the HP level was determined between these groups (P < .05). CONCLUSION: A single intraperitoneal dose of 5-FU had a preventive effect on stricture formation after caustic esophageal burn. This observation suggests that 5-FU may prevent this undesirable complication in the clinical setting. Clinical studies are now required to verify this form of treatment. Local intraesophageal application of 5-FU immediately after the burn injury was not effective. Further investigations are required to determine the appropriate timing of application of 5-FU at the local site of injury.
Assuntos
Queimaduras Químicas/tratamento farmacológico , Cáusticos/toxicidade , Estenose Esofágica/tratamento farmacológico , Fluoruracila/uso terapêutico , Hidróxido de Sódio/toxicidade , Animais , Diferenciação Celular , Divisão Celular , Cicatriz/etiologia , Cicatriz/prevenção & controle , Avaliação Pré-Clínica de Medicamentos , Estenose Esofágica/induzido quimicamente , Esôfago/química , Esôfago/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fibrose , Fluoruracila/administração & dosagem , Hidroxiprolina/análise , Injeções Intraperitoneais , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
BACKGROUND: Renal injury induced by aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute renal failure following abdominal aortic surgery. The purpose of this study is to examine the effect of erythropoietin on renal injury induced by aortic IR in rats. MATERIAL AND METHODS: Twenty-four Wistar-Albino rats were randomized into 3 groups (8 per group). The control group underwent laparotomy and dissection of the infrarenal abdominal aorta without occlusion. The aortic IR group underwent clamping of the infrarenal abdominal aorta for 30 min followed by 60 min of reperfusion. The aortic IR + erythropoietin group underwent the same aortic IR periods and was pretreated with 1000 U/kg subcutaneous erythropoietin 5 min before ischemia. In rat kidney specimens, tissue levels of malondialdehyde (MDA), superoxide dismutase, catalase, and glutathione peroxidase were measured. Histological evaluation of the rat kidney tissues was also done. RESULTS: Aortic IR significantly increased the levels of MDA and superoxide dismutase (P < 0.05 versus control). Erythropoietin significantly decreased the levels of MDA, superoxide dismutase, and catalase (P < 0.05 versus aortic IR). Histological evaluation showed that aortic IR significantly increased (P < 0.05 versus control), whereas erythropoietin significantly decreased (P < 0.05 versus aortic IR) the focal glomerular necrosis, dilation of Bowman's capsule, degeneration of tubular epithelium, necrosis in tubular epithelium, interstitial inflammatory infiltration, and congestion of blood vessels. CONCLUSIONS: The results indicate that erythropoietin has protective effects on renal injury induced by aortic IR in rats.
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Injúria Renal Aguda/prevenção & controle , Eritropoetina/uso terapêutico , Rim/enzimologia , Traumatismo por Reperfusão/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Aorta Abdominal , Catalase/metabolismo , Feminino , Glutationa Peroxidase/metabolismo , Rim/metabolismo , Rim/patologia , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVE: We searched the influence of dose and timing of atropine therapy in fenthion-induced pancreatitis model. METHODS: All rats were intoxicated with fenthion except the control group. Two milligrams of atropine was administered for 24 hours in a high dose atropine group while a low dose atropine group received 100 micrograms of atropine for 24 hours. One group received 2 milligrams of atropine in the first four hours of intoxication while the other group received 2 milligrams of atropine in the last four hours before sacrifice. All rats were sacrificed 24 hours after intoxication. Pseudo-cholinesterase and lipase concentrations and histopathological markers of pancreatitis were studied. RESULTS: None of the models in this study completely prevented pancreatitis, however high dose atropine that is administered for 24 hours or the first four hours after intoxication prevented severe pancreatitis. CONCLUSION: Atropine administration influence on fenthion-induced pancreatitis should be studied for other organophosphates in animals and humans.
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Atropina/uso terapêutico , Fention/toxicidade , Pâncreas/efeitos dos fármacos , Pancreatite/prevenção & controle , Animais , Atropina/administração & dosagem , Butirilcolinesterase/análise , Relação Dose-Resposta a Droga , Fention/administração & dosagem , Injeções Intraperitoneais , Injeções Subcutâneas , Lipase/análise , Organofosfatos/administração & dosagem , Organofosfatos/toxicidade , Pâncreas/enzimologia , Pâncreas/patologia , Pancreatite/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
BACKGROUND: [corrected] The goal of this experimental study was to investigate whether erdosteine has a protective effect against lung injury as a remote organ after hind-limb ischemia-reperfusion (I/R). MATERIALS AND METHODS: The rats were divided into three groups: control, I/R, and I/R + erdosteine. After the experimental procedure, nitric oxide (NO) levels, myeloperoxidase (MPO), adenosine deaminase (ADA), and the activities of xanthine oxidase (XO) were determined on the lung tissue. The levels of NO and activities of MPO were also measured on the bronchial alveolar lavage (BAL). In addition, the lung tissue was examined by histopathology. RESULTS: The lung tissue ADA and XO activities were increased in the I/R group compared with the control group (P < 0.05). In the I/R group, the levels of NO were higher than the control group (P < 0.05), whereas the erdosteine treatment did not alter the NO levels (P < 0.05). The MPO activities increased after I/R in the I/R group compared to both control and I/R + erdosteine group (P < 0.05). The activity of MPO increased in the IR group in comparison with the control group in BAL (P < 0.05). The activity of MPO in the I/R + erdosteine group was significantly lower than the I/R group in BAL (P < 0.05). NO levels increased in all I/R groups compared to control group in BAL (P < 0.05). However, treatment of erdosteine significantly decreased NO levels compared to I/R group (P < 0.05). The animals of the I/R group had total destruction of normal alveolar structure with the intense presence of infiltrating neutrophils and mononuclear phagocytes in histopathological examination. The rat lung exhibited mild degrees of destruction in the erdosteine group. CONCLUSIONS: As a result, erdosteine may be a protective effect for lung injury, decreasing oxidative stress and neutrophil accumulation after hind-limb I/R in rats.
Assuntos
Antioxidantes/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Tioglicolatos/farmacologia , Tiofenos/farmacologia , Adenosina Desaminase/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Membro Posterior , Masculino , Neutrófilos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Síndrome do Desconforto Respiratório/etiologia , Xantina Oxidase/metabolismoRESUMO
PURPOSE: The aim of this study was to examine the effects of Nomega-nitro-L-arginine methyl ester (L-NAME) and L-arginine on lung injury after aortic ischemia-reperfusion (IR). METHODS: Twenty-four Wistar-Albino rats were randomized into four groups (n = 6) as follows: Control (sham laparotomy), Aortic IR (30 min ischemia and 120 min reperfusion), L-Arginine (intraperitoneal 100 mg kg(-1) live weight)+aortic IR, and L: -NAME (intraperitoneal 10 mg kg(-1) live weight)+aortic IR. In the lung specimens, the tissue levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and nitric oxide (NO) were measured and a histological examination was done. RESULTS: Aortic IR increased MDA, VEGF, and NO. L-Arginine further significantly increased MDA and NO, and decreased VEGF (P < 0.05 vs aortic IR). L-NAME significantly decreased MDA and NO (P < 0.05 vs L-arginine+aortic IR) and increased VEGF (P < 0.05 vs other groups). A histological examination showed the aortic IR to significantly increase (P < 0.05 vs control) while L-arginine also further increased (P > 0.05 vs aortic IR), whereas L-NAME caused a significant decrease in pulmonary leukocyte infiltration (P < 0.05 vs aortic IR). CONCLUSIONS: Our results indicate that L-arginine aggravates the lung injury induced by aortic IR, while L-NAME attenuates it.
Assuntos
Aorta Abdominal , Arteriopatias Oclusivas/complicações , Inibidores Enzimáticos/uso terapêutico , NG-Nitroarginina Metil Éster/uso terapêutico , Traumatismo por Reperfusão/complicações , Síndrome do Desconforto Respiratório/tratamento farmacológico , Animais , Arginina/uso terapêutico , Biomarcadores/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/metabolismo , Espectrofotometria , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: Sepsis and ensuing multiorgan failure continue to be the major causes of mortality in intensive care units. Nuclear factor (NF)-kappaB activation is supposed to be one of the targets in the treatment of sepsis. We studied the effectiveness of caffeic phenethyl ester (CAPE), a known NF-kappaB inhibitor, in cecal ligation and puncture (CLP)-induced sepsis and lung injury. DESIGN: Randomized, controlled animal study. SETTING: Research laboratory of an academic institution. SUBJECTS: Female Sprague-Dawley rats. INTERVENTIONS: CLP was performed in all rats except the rats in control and sham+CAPE groups. CAPE was administered to rats at the time of operation in sham+CAPE and CAPE+sepsis 0 groups. CAPE was administered to rats in the CAPE+sepsis12 group 12 hrs after CLP. Eight rats from each group were killed 24 hrs after CLP. Blood was taken for assessment of interleukin-1, interleukin-6, interleukin-10, and tumor necrosis factor-alpha; the right lung was removed for histopathologic examination and the left lung for biochemical examination. Apoptosis, inducible nitric oxide synthase, heat shock protein 70, malondialdehyde, catalase, superoxide dismutase, and glutathione peroxidase were studied. The rest of the rats were observed for mortality. MEASUREMENTS AND MAIN RESULTS: Mortality was significantly decreased in groups that received CAPE compared with the sepsis group. All cytokine levels were similar to control levels only in the CAPE+sepsis12 group. Apoptosis, inducible nitric oxide synthase, and heat shock protein 70 evaluation were significantly changed between all groups in the following order: control < sham+CAPE< CAPE+sepsis12 < CAPE+sepsis 0 < sepsis. Malondialdehyde and catalase were increased in the sepsis group. CONCLUSIONS: CAPE reduced mortality in sepsis and improved histopathologic variables best when it was administered after the onset of sepsis.
Assuntos
Ácidos Cafeicos/uso terapêutico , NF-kappa B/antagonistas & inibidores , Álcool Feniletílico/análogos & derivados , Síndrome do Desconforto Respiratório/prevenção & controle , Sepse/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Ácidos Cafeicos/administração & dosagem , Ácidos Cafeicos/farmacologia , Citocinas/efeitos dos fármacos , Feminino , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Síndrome do Desconforto Respiratório/patologia , Sepse/patologia , Análise de SobrevidaRESUMO
BACKGROUND: To determine the levels of oxidative stress markers in pregnant women who snore and compare with non-snoring pregnant women. Fetal outcome of these 2 groups was also evaluated. MATERIALS AND METHODS: Prospective, case control study. Some 40 pregnant women who snored and 43 non-snoring pregnant women were evaluated. The glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and myeloperoxidase (MPO) levels of the 2 groups were studied. Infant birthweight, Apgar scores, and other indicators of fetal outcome were obtained. RESULTS: The mean level of GSH-Px was significantly lower in the pregnant women who snored (p=0.005), while the mean level of MDA was significantly higher in this group (p=0.005). Levels of MPO were comparable between the groups (p>0.05). The pregnant women who snored did not have infants with evidence of an increase in compromised outcome. CONCLUSION: Although the pregnant women who snored had high levels of MDA, they did not appear to be at increased risk for delivering infants with fetal compromise.
Assuntos
Glutationa Peroxidase/sangue , Malondialdeído/sangue , Estresse Oxidativo/fisiologia , Peroxidase/sangue , Complicações na Gravidez/metabolismo , Ronco/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Apneia Obstrutiva do Sono/metabolismoRESUMO
The aim of this study was to investigate the protective effects of erdosteine and vitamins C and E (VCE) on the lungs after performing hind limb ischemia-reperfusion (I/R) by assessing oxidative stress, plasma copper (Cu), and zinc (Zn) analysis. The animals were divided randomly into four groups as nine rats each as follows: control, I/R, I/R plus erdosteine, and I/R plus VCE combination. I/R period for 60 min was performed on the both hind limbs of all the rats in the groups of I/R, erdosteine with I/R, VCE with I/R allowing 120 min of reperfusion. The animals received orally erdosteine one time in a day and 3 days before I/R in the erdosteine group. In the VCE group, the animals VCE combination received one time in a day and 3 days before I/R, although placebo was given to control and I/R group animals. Lung lipid peroxidation (malondialdehyde [MDA]) level, superoxide dismutase (SOD), and catalase activities were increased, although lung glutathione (GSH) and plasma Zn levels decreased in I/R group in lung tissue compared with the control group. Serum MDA level, creatine kinase, and lactate dehydrogenase activities were increased in I/R group compared with the control. Lung MDA and plasma Zn levels and lung SOD activity were decreased by erdosteine administration, whereas lung GSH levels after I/R increased. The plasma Zn levels and lung SOD activity were decreased by VCE administration, although the plasma Cu and lung GSH levels increased after I/R. In conclusion, erdosteine has an antioxidant role on the values in the rat model, and it has more protective affect than in VCE in attenuating I/R-induced lung injury in rats.
Assuntos
Ácido Ascórbico/metabolismo , Cobre/sangue , Pulmão/metabolismo , Substâncias Protetoras/metabolismo , Traumatismo por Reperfusão/sangue , Tioglicolatos/metabolismo , Tiofenos/metabolismo , Vitamina E/metabolismo , Zinco/sangue , Animais , Antioxidantes/metabolismo , Creatina Quinase/metabolismo , Expectorantes/metabolismo , Glutationa/metabolismo , L-Lactato Desidrogenase/metabolismo , Extremidade Inferior , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
We have investigated the effect of subchronic administration of methidathion (MD) on ovary evaluated ameliorating effects of vitamins E and C against MD toxicity. Experimental groups were as follows: control group; a group treated with 5 mg/kg body weight MD (MD group); and a group treated with 5 mg/kg body weight MD plus vitamin E and vitamin C (MD + Vit group). MD and MD + Vit groups were given MD by gavage five days a week for four weeks at a dose level of 5 mg/kg/day by using corn oil as the vehicle. Serum malondialdehyde (MDA: an indicator of lipid peroxidation) concentration, serum activity of cholinesterase (ChE), and ovary histopathology were studied. The level of MDA increased significantly in the MD group compared with the control (P < 0.005). Serum MDA decreased significantly in the MD + Vit group compared with the MD group (P < 0.05). The activities of ChE decreased significantly both in the MD and MD + Vit groups compared with the controls ( P < 0.05). However, the decrease in the MD + Vit groups was less than in the MD group; the ChE activity in the MD + Vit group was significantly higher compared with MD group (P < 0.05). Number of ovarian follicles were significantly lower in the MD group compared to the controls (P < 0.05). Number of atretic follicles were significantly higher in the MD group than in the controls (P < 0.05). Follicle counts in MD + Vit group showed that all types of ovarian follicles were significantly higher, and a significant decrease in the number of atretic follicles compared with the MD group (P < 0.05). In conclusion, subchronic MD administration caused an ovarian damage, in addition, LPO may be one of the molecular mechanisms involved in MD-induced toxicity. Treatment with vitamins E and C after the administration of MD reduced LPO and ovarian damage.
Assuntos
Ácido Ascórbico/uso terapêutico , Compostos Organotiofosforados/toxicidade , Doenças Ovarianas/induzido quimicamente , Doenças Ovarianas/tratamento farmacológico , alfa-Tocoferol/análogos & derivados , Administração Oral , Animais , Ácido Ascórbico/administração & dosagem , Colinesterases/metabolismo , Corpo Lúteo/efeitos dos fármacos , Corpo Lúteo/metabolismo , Corpo Lúteo/patologia , Esquema de Medicação , Quimioterapia Combinada , Ciclo Estral/efeitos dos fármacos , Fadiga/induzido quimicamente , Feminino , Injeções Intraperitoneais , Inseticidas/toxicidade , Intubação Gastrointestinal , Malondialdeído/sangue , Doenças Ovarianas/sangue , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Ratos , Ratos Wistar , Tocoferóis , Vitaminas/administração & dosagem , Vitaminas/uso terapêutico , Aumento de Peso/efeitos dos fármacos , Redução de Peso/efeitos dos fármacos , alfa-Tocoferol/administração & dosagem , alfa-Tocoferol/uso terapêuticoRESUMO
Reactive oxygen species caused by organophosphates may be involved in the toxicity of various pesticides. Therefore, in this study, we aimed to investigate the effects of acute exposure to organophosphate insecticide diazinon (DI) and possible ameliorating role of vitamins E and C, with the following parameters: lipid peroxidation (LPO) and the activity of the glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in rat erythrocytes. The experimental groups were arranged as control group, DI-treated group (DI) and DI + vitamin E + vitamin C-treated group (DI + Vit). DI + Vit groups were treated orally with a single dose of 335 mg/kg DI body weight. Vitamins E and C were injected at doses of 150 mg/kg body weight intramuscular (in) and 200 mg/kg body weight intraperitoneal (ip), respectively, 30 min after the treatment of DI in DI + Vit group. Blood samples were taken 24 h after the DI. The results showed that DI administration caused to increase in LPO and the activities of SOD and GSH-Px enzymes in erythrocytes. Also, the combination of vitamins E and C decreased LPO and the activities of GSH-Px and SOD compared with the DI group. In conclusion, although treating rats with single dose DI increases LPO and antioxidant enzyme activities in erythrocytes, vitamins C and E combination can reduce LPO caused by DI.
Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Diazinon/toxicidade , Eritrócitos/efeitos dos fármacos , Glutationa Peroxidase/efeitos dos fármacos , Inseticidas/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Análise Química do Sangue , Combinação de Medicamentos , Glutationa Peroxidase/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
We studied the influence of dose and timing of atropine therapy on fenthion-induced organ dysfunction. Thirty-six rats were randomized into six groups. All rats in the five groups except the control group were intoxicated with fenthion. The high-dose atropine group received 2 mg/kg of atropine, whereas the low-dose group received 100 microg/kg of atropine every hour for 24 hr. One group received 2 mg/kg of atropine in the first 4 hr of intoxication while the other group received 2 mg/kg of atropine in the last 4 hr before killed, which for all rats was 24 hr after intoxication. Pseudocholinesterase and aspartate aminotransferase and alanine aminotransferase levels and histopathological markers of lung, brain and liver were studied. None of our atropine therapy strategies in this study totally prevented harm on the three organs. Although the high dose of atropine administered for 24 hr had the least harmful markers for lung, it also had the most harmful markers for brain and liver. We did not succeed in finding a unique therapy strategy in our models beneficial for all studied organs in fenthion intoxication in rats. Atropine administration strategy should be oriented for the most affected organ pathology in fenthion intoxication.