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Acta cir. bras ; 34(7): e201900706, 2019. tab, graf
Article in English | LILACS | ID: biblio-1038113


Abstract Purpose: To investigate the protective roles of pyracantha fortune fruit extract (PFE) on acute renal toxicity induced by cadmium chloride (CdCl2) in rats. Methods: Rats were pretreated with PFE and consecutively injected with CdCl2 (6.5 mg/kg) for 5 days. Results: The concentration of Cd, kidney weight, malondialdehyde (MDA), and nitric oxide (NO) production were remarkably increased in CdCl2 group as well as the levels of plasma uric acid, urea, and creatinine (P < 0.001). However, the body weight and glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione peroxidase (GR) levels were markedly reduced by CdCl2 treatment (P < 0.001). Histological manifestations of renal tissue showed severely adverse changes. Moreover, CdCl2 treatment significantly decreased the B-cell lymphoma-2 (Bcl-2) expression while increased the Bcl-2-Associated X Protein (Bax), tumor necrosis factor-α (TNF-α) expression (P < 0.001). Additionally, the expression of Nrf2/Keap 1 related proteins Keap-1 gained a significant increase (P < 0.001), whereas the Nrf2, HO-1, γ-GCS, GSH-Px and NQO1 expression decreased by CdCl2 treatment (P < 0.05). These rats were pretreated with PFE to improve the changes caused by CdCl2 treatment. Conclusion: PFE could protect the kidney against acute renal toxicity induced by CdCl2.

Animals , Male , Rats , Plant Extracts/pharmacology , Cadmium Chloride/toxicity , Pyracantha/chemistry , Chemical and Drug Induced Liver Injury/prevention & control , Kidney/drug effects , Antioxidants/pharmacology , Superoxide Dismutase/metabolism , Catalase/metabolism , Oxidative Stress/drug effects , Disease Models, Animal , Fruit/chemistry , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Kidney/pathology
Braz. j. microbiol ; 49(3): 513-521, July-Sept. 2018. tab, graf
Article in English | LILACS | ID: biblio-951812


Abstract Soil salinity is an important abiotic stress worldwide, and salt-induced oxidative stress can have detrimental effects on the biological nitrogen fixation. We hypothesized that co-inoculation of cowpea plants with Bradyrhizobium and plant growth-promoting bacteria would minimize the deleterious effects of salt stress via the induction of enzymatic and non-enzymatic antioxidative protection. To test our hypothesis, cowpea seeds were inoculated with Bradyrhizobium or co-inoculated with Bradyrhizobium and plant growth-promoting bacteria and then submitted to salt stress. Afterward, the cowpea nodules were collected, and the levels of hydrogen peroxide; lipid peroxidation; total, reduced and oxidized forms of ascorbate and glutathione; and superoxide dismutase, catalase and phenol peroxidase activities were evaluated. The sodium and potassium ion concentrations were measured in shoot samples. Cowpea plants did not present significant differences in sodium and potassium levels when grown under non-saline conditions, but sodium content was strongly increased under salt stress conditions. Under non-saline and salt stress conditions, plants co-inoculated with Bradyrhizobium and Actinomadura or co-inoculated with Bradyrhizobium and Paenibacillus graminis showed lower hydrogen peroxide content in their nodules, whereas lipid peroxidation was increased by 31% in plants that were subjected to salt stress. Furthermore, cowpea nodules co-inoculated with Bradyrhizobium and plant growth-promoting bacteria and exposed to salt stress displayed significant alterations in the total, reduced and oxidized forms of ascorbate and glutathione. Inoculation with Bradyrhizobium and plant growth-promoting bacteria induced increased superoxide dismutase, catalase and phenol peroxidase activities in the nodules of cowpea plants exposed to salt stress. The catalase activity in plants co-inoculated with Bradyrhizobium and Streptomyces was 55% greater than in plants inoculated with Bradyrhizobium alone, and this value was remarkably greater than that in the other treatments. These results reinforce the beneficial effects of plant growth-promoting bacteria on the antioxidant system that detoxifies reactive oxygen species. We concluded that the combination of Bradyrhizobium and plant growth-promoting bacteria induces positive responses for coping with salt-induced oxidative stress in cowpea nodules, mainly in plants co-inoculated with Bradyrhizobium and P. graminis or co-inoculated with Bradyrhizobium and Bacillus.

Sodium Chloride/metabolism , Bradyrhizobium/physiology , Agricultural Inoculants/physiology , Vigna/microbiology , Antioxidants/metabolism , Plant Proteins/metabolism , Stress, Physiological , Superoxide Dismutase/metabolism , Lipid Peroxidation , Catalase/metabolism , Peroxidase/metabolism , Oxidative Stress , Salinity , Vigna/growth & development , Vigna/metabolism , Glutathione/metabolism
Biol. Res ; 51: 17, 2018. graf
Article in English | LILACS | ID: biblio-950903


BACKGROUND: Improper control on reactive oxygen species (ROS) elimination process and formation of free radicals causes tissue dysfunction. Pineal hormone melatonin is considered a potent regulator of such oxidative damage in different vertebrates. Aim of the current communication is to evaluate the levels of oxidative stress and ROS induced damage, and amelioration of oxidative status through melatonin induced activation of signaling pathways. Hepatocytes were isolated from adult Labeo rohita and exposed to H2O2 at three different doses (12.5, 25 and 50 µM) to observe peroxide induced damage in fish hepatocytes. Melatonin (25, 50 and 100 µg/ml) was administered against the highest dose of H2O2. Enzymatic and non-enzymatic antioxidants such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) was measured spectrophotometrically. Expression level of heat shock proteins (HSP70 and HSP90), HSPs-associated signaling molecules (Akt, ERK, cytosolic and nuclear NFkB), and melatonin receptor was also measured by western blotting analysis. RESULTS: H2O2 induced oxidative stress significantly altered (P < 0.05) MDA and GSH level, SOD and CAT activity, and up regulated HSP70 and HSP90 expression in carp hepatocytes. Signaling proteins exhibited differential modulation as revealed from their expression patterns in H2O2-exposed fish hepatocytes, in comparison with control hepatocytes. Melatonin treatment of H2O2-stressed fish hepatocytes restored basal cellular oxidative status in a dose dependent manner. Melatonin was observed to be inducer of signaling process by modulation of signaling molecules and melatonin receptor. CONCLUSIONS: The results suggest that exogenous melatonin at the concentration of 100 µg/ml is required to improve oxidative status of the H2O2-stressed fish hepatocytes. In H2O2 exposed hepatocytes, melatonin modulates expression of HSP70 and HSP90 that enable the hepatocytes to become stress tolerant and survive by altering the actions of ERK, Akt, cytosolic and nuclear NFkB in the signal transduction pathways. Study also confirms that melatonin could act through melatonin receptor coupled to ERK/Akt signaling pathways. This understanding of the mechanism by which melatonin regulates oxidative status in the stressed hepatocytes may initiate the development of novel strategies for hepatic disease therapy in future.

Animals , Signal Transduction/drug effects , Oxidative Stress/drug effects , Hepatocytes/drug effects , Hydrogen Peroxide/pharmacology , Melatonin/pharmacology , Spectrophotometry , Superoxide Dismutase/drug effects , Catalase/drug effects , Catalase/metabolism , Blotting, Western , NF-kappa B/drug effects , NF-kappa B/metabolism , Reactive Oxygen Species/metabolism , MAP Kinase Signaling System/drug effects , Hepatocytes/metabolism , Proto-Oncogene Proteins c-akt/drug effects , Fishes , Glutathione/drug effects , Glutathione/metabolism , Malondialdehyde/metabolism
Acta cir. bras ; 31(8): 557-563, Aug. 2016. tab, graf
Article in English | LILACS | ID: lil-792413


ABSTRACT PURPOSE: To determine the toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproductive system and the beneficial effects of Montelukast (ML) with histological and biochemical analysis. METHODS: Rats were randomly divided into four equal groups (control, TCDD, ML and TCDD+ML). Tissue samples were collected on day 60 and oxidative status and histological alterations were analyzed. RESULTS: The results showed a significant increase in oxidative and histological damage on uterine and ovarian tissues. Otherwise, the oxidative and histological damages caused by TCDD were prevented with ML treatment. CONCLUSION: The toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on female reproductive system were reversed with Montelukast treatment. Therefore, we claimed that ML treatment might be useful for TCDD toxicity.

Animals , Female , Rats , Ovary/drug effects , Quinolines/pharmacology , Oxidative Stress/drug effects , Polychlorinated Dibenzodioxins/toxicity , Acetates/pharmacology , Antioxidants/pharmacology , Ovary/pathology , Superoxide Dismutase/metabolism , Uterus/pathology , Catalase/metabolism , Random Allocation , Rats, Wistar , Glutathione/metabolism , Ovarian Follicle/drug effects
Acta cir. bras ; 31(7): 456-462, tab, graf
Article in English | LILACS | ID: lil-787264


ABSTRACT PURPOSE: To investigate the protective effect of β-myrcene (MYR) on oxidative and histological damage in mice heart tissue caused global cerebral ischemia/reperfusion (IR) in C57BL/J6 mice. METHODS: Animals(n=40) were randomly divided into four groups: (1)control, (2)IR, (3)MYR and (4)MYR+IR. The control group was received 0.1% carboxymethyl cellulose as a vehicle following a medial incision without carotid occlusion. In the IR group, the bilateral carotid arteries were clipped for 15min, and treated with the vehicle intraperitoneally(ip) for 10 days. MYR (200mg/kg) was received dissolved in 0.1%CMC for 10 days. In the MYR+IR group, the IR model was applied exactly as in the IR group, and then they were treated with MYR 10 days. RESULTS: The cerebral IR caused oxidative damage (increase TBARS, decrease antioxidant parameters). Treatment of MYR was increased in GSH,GPx,CAT,SOD activity while TBARS level was decreased. In addition, degenerative changes in I/R group heart tissue were ameliorated by MYR administration. CONCLUSİON: The administration of β-myrcene protects oxidative and histological damage in the heart tissue after global ischemia-reperfusion and may be useful safe alternative treatment for cardiac tissue after ischemic stroke.

Animals , Male , Cardiotonic Agents/pharmacology , Reperfusion Injury/complications , Brain Ischemia/complications , Monoterpenes/pharmacology , Heart/drug effects , Antioxidants/pharmacology , Superoxide Dismutase/metabolism , Catalase/metabolism , Random Allocation , Thiobarbituric Acid Reactive Substances/metabolism , Oxidative Stress/drug effects , Models, Animal , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Mice, Inbred C57BL , Myocardium/metabolism , Myocardium/pathology
Acta cir. bras ; 31(3): 168-175, Mar. 2016. graf
Article in English | LILACS | ID: lil-777089


ABSTRACT PURPOSE : To investigate the effects of thiamine pyrophosphate (TPP) against desflurane induced hepatotoxicity. METHODS : Thirty experimental animals were divided into groups as healthy (HG), desflurane control (DCG) , TPP and desflurane group (TDG). 20 mg/kg TPP was injected to intraperitoneally TDG. After one hour of TPP administration, desflurane was applied for two hours. After 24 hours, liver tissues of the animals killed with decapitation were removed. The oxidant/antioxidant levels and ALT, AST and LDH activities were measured. The histopathological examinations were performed in the liver tissues for all rats. RESULTS : Notwithstanding the levels of oxidants and liver enzymes were significantly increased (p<0.0001), antioxidant levels were significantly decreased in DCG (p<0.0001). On contrary to the antioxidant parameters were increased (p<0.05) the oxidant parameters and liver enzymes were decreased in TDG (p<0.0001). Whereas multiple prominent, congestion, hemorrhage and dilatation were observed in sinusoids and lymphocyte-rich inflammation results in the centrilobular and portal areas of liver tissue in DCG, these findings were observed less frequently in TDG. CONCLUSİON : Thiamine pyrophosphate prevented liver oxidative damage induced with desflurane and may be useful in prophylaxis of desflurane induced hepatotoxicity.

Animals , Male , Thiamine Pyrophosphate/therapeutic use , Anesthetics, Inhalation/adverse effects , Protective Agents/pharmacology , Chemical and Drug Induced Liver Injury/prevention & control , Isoflurane/analogs & derivatives , Aspartate Aminotransferases/drug effects , Aspartate Aminotransferases/metabolism , Rats, Wistar , Peroxidase/drug effects , Oxidative Stress/drug effects , Alanine Transaminase/drug effects , Alanine Transaminase/metabolism , Chemical and Drug Induced Liver Injury/metabolism , Glutathione/drug effects , Glutathione/metabolism , Isoflurane , L-Lactate Dehydrogenase/drug effects , L-Lactate Dehydrogenase/metabolism , Liver/enzymology , Liver/pathology , Malondialdehyde/metabolism , Nitric Oxide/metabolism
Yonsei Medical Journal ; : 1252-1259, 2016.
Article in English | WPRIM | ID: wpr-79766


PURPOSE: Diabetic nephropathy (DN) is a prevalent chronic microvascular complication of diabetes mellitus involving disturbances in electrolytes and the acid-base balance caused by a disorder of glucose metabolism. NHE1 is a Na+/H+ exchanger responsible for keeping intracellular pH (pHi) balance and cell growth. Our study aimed to investigate roles of NHE1 in high glucose (HG)-induced apoptosis in renal tubular epithelial cells. MATERIALS AND METHODS: Renal epithelial tubular cell line HK-2 was cultured in medium containing 5 mM or 30 mM glucose. Then, cell apoptosis, oxidative stress, NHE1 expression, and pHi were evaluated. NHE1 siRNA and inhibitor were used to evaluate its role in cell apoptosis. RESULTS: HG significantly increased cell apoptosis and the production of reactive oxygen species (ROS) and 8-OHdG (p<0.05). Meanwhile, we found that HG induced the expression of NHE1 and increased the pHi from 7.0 to 7.6 after 48 h of incubation. However, inhibiting NHE1 using its specific siRNA or antagonist DMA markedly reduced cell apoptosis stimulated by HG. In addition, suppressing cellular oxidative stress using antioxidants, such as glutathione and N-acetyl cysteine, significantly reduced the production of ROS, accompanied by a decrease in NHE1. We also found that activated cyclic GMP-Dependent Protein Kinase Type I (PKG) signaling promoted the production of ROS, which contributed to the regulation of NHE1 functions. CONCLUSION: Our study indicated that HG activates PKG signaling and elevates the production of ROS, which was responsible for the induction of NHE1 expression and dysfunction, as well as subsequent cell apoptosis, in renal tubular epithelial cells.

Antioxidants/metabolism , Apoptosis/drug effects , Cation Transport Proteins/metabolism , Cell Cycle/drug effects , Cell Line , Dose-Response Relationship, Drug , Epithelial Cells/cytology , Glucose/pharmacology , Glutathione/metabolism , Humans , Kidney Tubules/cytology , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Sodium-Hydrogen Exchangers/metabolism
Braz. j. med. biol. res ; 48(9): 798-804, Sept. 2015. ilus
Article in English | LILACS | ID: lil-756403


Stroke is the third most common cause of death worldwide, and most stroke survivors present some functional impairment. We assessed the striatal oxidative balance and motor alterations resulting from stroke in a rat model to investigate the neuroprotective role of physical exercise. Forty male Wistar rats were assigned to 4 groups: a) control, b) ischemia, c) physical exercise, and d) physical exercise and ischemia. Physical exercise was conducted using a treadmill for 8 weeks. Ischemia-reperfusion surgery involved transient bilateral occlusion of the common carotid arteries for 30 min. Neuromotor performance (open-field and rotarod performance tests) and pain sensitivity were evaluated beginning at 24 h after the surgery. Rats were euthanized and the corpora striata was removed for assay of reactive oxygen species, lipoperoxidation activity, and antioxidant markers. Ischemia-reperfusion caused changes in motor activity. The ischemia-induced alterations observed in the open-field test were fully reversed, and those observed in the rotarod test were partially reversed, by physical exercise. Pain sensitivity was similar among all groups. Levels of reactive oxygen species and lipoperoxidation increased after ischemia; physical exercise decreased reactive oxygen species levels. None of the treatments altered the levels of antioxidant markers. In summary, ischemia-reperfusion resulted in motor impairment and altered striatal oxidative balance in this animal model, but those changes were moderated by physical exercise.

Animals , Male , Rats , Brain Ischemia/complications , Corpus Striatum/metabolism , Motor Disorders/prevention & control , Oxidative Stress/physiology , Physical Conditioning, Animal/physiology , Reperfusion Injury/complications , Brain Ischemia/metabolism , Catalase/metabolism , Disease Models, Animal , Glutathione/metabolism , Lipid Peroxidation , Motor Disorders/etiology , Oxidation-Reduction , Pain/physiopathology , Rats, Wistar , Reactive Oxygen Species/analysis , Superoxide Dismutase/metabolism
Rev. cuba. invest. bioméd ; 34(2): 168-186, abr.-jun. 2015. ilus
Article in Spanish | LILACS, CUMED | ID: lil-769441


La enfermedad de Parkinson es una enfermedad neurodegenerativa crónica que afecta a las personas de la tercera edad. En una minoría de los casos la enfermedad es de origen genético pero en el resto, la causa es idiopática. En este sentido, la acumulación de los radicales libres y la pérdida de la homeostasis del glutatión se han señalado como posibles agentes causales. El presente texto se propuso revisar las evidencias experimentales que apoyan la participación de los radicales libres y la pérdida de la homeostasis del glutatión en el comienzo y la progresión de la degeneración de la substantianigrapars compacta. El estrés oxidativo en la enfermedad de Parkinson´s puede estar relacionado con las propiedades pro-oxidantes intrínsecas de la dopamina y elevadas concentraciones de hierro en la substantianigrapars compacta, que promueven la oxidación de la dopamina y la generación de especies reactivas del oxígeno. Cualquier evento que desencadene estos mecanismos, genera un daño celular. La disminución del glutatión es una de las alteraciones bioquímicas más tempranas, detectadas en asociación con la enfermedad de Parkinson y se ha relacionado con la inhibición del complejo I de la cadena de transporte mitocondrial, daño oxidativo, activación glial, entre otros que favorecen la neurodegeneración. Estas evidencias sugieren la necesidad de mantener la homeostasis del glutatión en el sistema dopaminérgico y su vínculo con la etiología de la degeneración nigro-estriatal, lo que tiene una potencial aplicación en la práctica clínica.

Parkinson's disease is a chronic neurodegenerative condition affecting elderly persons. In a minority of cases the disease has a genetic origin, but in most the cause is idiopathic. Accumulation of free radicals and loss of glutathione homeostasis have been pointed at as possible causal agents. The purpose of the study was to review experimental evidence supporting the involvement of free radicals and loss of glutathione homeostasis in the outset and progress of substantia nigra pars compacta degeneration. Oxidative stress in Parkinson's disease may be related to the intrinsic pro-oxidant properties of dopamine and high iron concentrations in the substantia nigra pars compacta, promoting dopamine oxidation and the generation of reactive oxygen species. Any event triggering these mechanisms will cause cell damage. Glutathione reduction is one of the earliest biochemical alterations detected in association with Parkinson's disease, and it has been related to the inhibition of complex I of the mitochondrial transport chain, oxidative damage and glial activation, among other factors leading to neurodegeneration. This evidence points to the need to maintain glutathione homeostasis in the dopaminergic system, as well as its relationship to the etiology of nigrostriatal degeneration, of potential application in clinical practice.

Humans , Aged , Parkinson Disease/ethnology , Oxidative Stress , Free Radicals/metabolism , Glutathione/metabolism , Homeostasis
Clinics ; 70(5): 373-379, 05/2015. tab, graf
Article in English | LILACS | ID: lil-748273


OBJECTIVE: Intestinal ischemia-reperfusion injury occurs in several clinical conditions and after intestinal transplantation. The aim of the present study was to investigate the phenomena of apoptosis and cell proliferation in a previously described intestinal ischemia-reperfusion injury autograft model using immunohistochemical markers. The molecular mechanisms involved in ischemia-reperfusion injury repair were also investigated by measuring the expression of the early activation genes c-fos and c-jun, which induce apoptosis and cell proliferation. MATERIALS AND METHODS: Thirty adult male Wistar rats were subjected to surgery for a previously described ischemia-reperfusion model that preserved the small intestine, the cecum and the ascending colon. Following reperfusion, the cecum was harvested at different time points as a representative segment of the intestine. The rats were allocated to the following four subgroups according to the reperfusion time: subgroup 1: 5 min; subgroup 2: 15 min; subgroup 3: 30 min; and subgroup 4: 60 min. A control group of cecum samples was also collected. The expression of c-fos, c-jun and immunohistochemical markers of cell proliferation and apoptosis (Ki67 and TUNEL, respectively) was studied. RESULTS: The expression of both c-fos and c-jun in the cecum was increased beginning at 5 min after ischemia-reperfusion compared with the control. The expression of c-fos began to increase at 5 min, peaked at 30 min, and exhibited a declining tendency at 60 min after reperfusion. A progressive increase in c-jun expression was observed. Immunohistochemical analyses confirmed these observations. CONCLUSION: The early activation of the c-fos and c-jun genes occurred after intestinal ischemia-reperfusion injury, and these genes can act together to trigger cell proliferation and apoptosis. .

Animals , Mice , Rats , Endoplasmic Reticulum Stress , Fatty Acids/metabolism , Hepatocytes/physiology , Unfolded Protein Response , Acetylcysteine/metabolism , Cell Line, Tumor , Cells, Cultured , Glutathione/metabolism , Hepatocytes/metabolism , Oxidation-Reduction , Protein Folding
Ciênc. saúde coletiva ; 20(1): 199-208, 01/2015.
Article in English | LILACS, BDS | ID: lil-733149


The present article investigates the role of Haitian community radios in strengthening social mobilization, with the aim of supporting the actions undertaken in the field of public health in Haiti, based on the development of the Workshop for community radios, as part of the Tripartite Cooperation Brazil-Cuba-Haiti. The qualitative methodology is justified because of the study content, an analysis of documents and direct observation, through a case study presented at the Workshop held in the department of Hinches, in Haiti. This meeting was held in the context of the Working Group on Tripartite Communication, under the responsibility of the Health Channel/Fiocruz, in partnership with the Department for Health Promotion and Environmental Prevention of the Ministry of Health and Population of Haiti (DPSPE/MSPP/Haiti), with a proposal to better structure a network of multipliers in health promotion.

O presente artigo investiga o papel das rádios comunitárias haitianas no fortalecimento da mobilização social com a finalidade de subsidiar as ações empreendidas no campo da saúde pública no Haiti a partir da construção e do desenvolvimento da Oficina para rádios comunitárias, no âmbito da Cooperação Tripartite Brasil-Cuba-Haiti. A metodologia de cunho qualitativo justifica-se pelo teor do estudo, de análise de documentos e da observação direta, mediante estudo de caso a partir da Oficina, realizada no departamento de Hinches, no Haiti. O encontro foi realizado no âmbito do Grupo de Trabalho de Comunicação da Tripartite, sob a responsabilidade do Canal Saúde/Fiocruz, em parceria com o Departamento de Promoção da Saúde e Prevenção do Meio Ambiente do Ministério da Saúde e População do Haiti (DPSPE/MSPP/Haiti), com a proposta de estruturar uma rede de multiplicadores de promoção da saúde.

Animals , Female , Rats , Antioxidants/pharmacology , Liver/pathology , Phosphoric Acids/pharmacology , Tungsten Compounds/pharmacology , Acute Disease , Administration, Oral , Carbon Tetrachloride , Disease Models, Animal , Glutathione/metabolism , Liver Function Tests , Liver/drug effects , Necrosis/chemically induced , Necrosis/drug therapy , Necrosis/physiopathology , Oxidative Stress/drug effects , Rats, Wistar , Thioacetamide
Article in English | WPRIM | ID: wpr-157202


BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines. METHODS: Western blotting was used to measure P53 expression. The effects of radiotherapy with iodine-131 were assessed by using the clonogenic assay to evaluate cell survival. Flow cytometry was carried out to examine the effects of iodine-131 on cell death, oxidative stress, reduced intracellular glutathione expression, the mitochondrial membrane potential, and the cell cycle. RESULTS: The P53 protein was not expressed in Hep3B2.1-7 cells, was expressed at normal levels in HepG2 cells, and was overexpressed in HuH7 cells. P53 expression in the HuH7 and HepG2 cell lines increased after internal and external irradiation with iodine-131. Irradiation induced a decrease in cell survival and led to a decrease in cell viability in all of the cell lines studied, accompanied by cell death via late apoptosis/necrosis and necrosis. Irradiation with 131-iodine induced mostly cell-cycle arrest in the G0/G1 phase. CONCLUSIONS: These results suggest that P53 plays a key role in the radiotherapy response of HCC.

Apoptosis/radiation effects , Blotting, Western , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Survival/drug effects , G1 Phase Cell Cycle Checkpoints/radiation effects , Gamma Rays , Glutathione/metabolism , Hep G2 Cells , Humans , Iodine Radioisotopes/chemistry , Liver Neoplasms/metabolism , Phosphorylation , Reactive Oxygen Species/metabolism , Tumor Suppressor Protein p53/metabolism
Article in English | WPRIM | ID: wpr-42471


Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.

Animals , Antioxidants/metabolism , Apoptosis/drug effects , Caspase 3/metabolism , Caspase 8/metabolism , Cell Line , Cisplatin/toxicity , Cysteine/analogs & derivatives , Gene Expression Regulation/drug effects , Gene Knockdown Techniques , Glutathione/metabolism , Heme Oxygenase-1/genetics , Intracellular Space/metabolism , Male , Metabolic Detoxication, Phase II/genetics , Mice , NF-E2-Related Factor 2/genetics , Nitric Oxide/biosynthesis , Organ of Corti/drug effects , RNA Interference , Rats , Reactive Oxygen Species/metabolism , Superoxide Dismutase/genetics
Rev. bras. parasitol. vet ; 23(4): 428-434, Oct-Dec/2014. tab, graf
Article in English | LILACS | ID: lil-731249


Three hemoplasma species are recognized in domestic cats: Mycoplasma haemofelis, ‘Candidatus Mycoplasma haemominutum’ and ‘Candidatus Mycoplasma turicensis’. We report the prevalence and hematological abnormalities of hemoplasma infection in 369 domestic cats from three different populations (blood donors, hospitalized cats and shelter cats) from Southern Brazil. Complete blood counts were performed at the time of blood collection, and DNA was extracted and tested by conventional PCR for each hemoplasma species. A total of 79 samples (21.40%) were positive for at least one species. The most prevalent hemoplasma was ‘Candidatus Mycoplasma haemominutum’, with 50/369 (13.55%) positive cats, followed by ‘Candidatus Mycoplasma turicensis’, 10/369 (2.71%), and Mycoplasma haemofelis, 8/369 (2.16%). Mycoplasma haemofelis and ‘Candidatus Mycoplasma haemominutum’ coinfection was observed in 4/369 (1.08%), whereas ‘Candidatus Mycoplasma haemominutum’ and ‘Candidatus Mycoplasma turicensis’ in 5/369 (1.35%). Three cats (0.81%) were infected with all three hemoplasmas. There was no association between infection and the different populations. Anemia was associated with Mycoplasma haemofelis and ‘Candidatus Mycoplasma haemominutum’, but not with ‘Candidatus Mycoplasma turicensis’. Male cats and cats with outdoor access were more likely to be infected. Although ‘Candidatus Mycoplasma haemominutum’ is believed to cause minimal or no hematological alterations, the infected cats studied herein were more likely to be anemic.

Três espécies de hemoplasmas são reconhecidas em gatos domésticos: Mycoplasma haemofelis, ‘Candidatus Mycoplasma haemominutum’ e ‘Candidatus Mycoplasma turicensis’. A prevalência e alterações hematológicas associadas à infecção por hemoplasmas foi estudada, em 369 gatos domésticos de três populações distintas (doadores de sangue, hospitais e gatos de abrigo) do Sul do Brasil. Foram realizados hemogramas completos no momento da coleta de sangue e as amostras tiveram seu DNA extraído e testado por PCR convencional para cada espécie de hemoplasmas. Setenta e nove amostras (21,40%) foram positivas para pelo menos uma espécie. O mais prevalente foi ‘Candidatus Mycoplasma haemominutum’ com 50/369 (13,55%) gatos positivos, seguidos por ‘Candidatus Mycoplasma turicensis’ com 10/369 (2,71%) e Mycoplasma haemofelis com 8/369 (2,16%). Coinfecção por Mycoplasma haemofelis e ‘Candidatus Mycoplasma haemominutum’ foi observada em 4/369 (1,08%), enquanto ‘Candidatus Mycoplasma haemominutum’ e ‘Candidatus Mycoplasma turicensis’ coinfectaram 5/369 (1,35%) gatos. Três (0,81%) gatos apresentaram infecção pelos três hemoplasmas. Não houve associação entre a infecção e as diferentes populações. Anemia foi associada com a infecção por Mycoplasma haemofelis e ‘Candidatus Mycoplasma haemominutum’, mas não com ‘Candidatus Mycoplasma turicensis’. Gatos machos e com acesso à rua apresentaram maior probabilidade de serem infectados. Embora se acredite que ‘Candidatus Mycoplasma haemominutum’ possa causar alterações hematológicas mínimas ou ausentes, gatos infectados encontrados neste estudo foram mais propensos à anemia.

Animals , Male , Rats , Hepatocytes/drug effects , Mitochondria, Liver/drug effects , NAD(P)H Dehydrogenase (Quinone)/metabolism , Oxidative Stress/drug effects , Ubiquinone/pharmacology , Cells, Cultured , Cytoprotection , Cell Membrane/drug effects , Cell Survival/drug effects , Glutathione/metabolism , Hepatocytes/enzymology , Membrane Potentials/drug effects , Mitochondria, Liver/enzymology , NAD , Oxidation-Reduction , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Rotenone/toxicity , Uncoupling Agents/toxicity , /pharmacology
Acta cir. bras ; 29(11): 742-747, 11/2014. graf
Article in English | LILACS | ID: lil-728644


PURPOSE: We evaluated the hypothesis that induced perioperative hypothermia (32 ± 1ºC) affects the redox balance in the tissue of colonic anastomosis in rats by modifying biochemical enzymatic and non-enzymatic markers related to oxidative stress. METHODS: Forty-eight male Wistar rats were randomly divided into eight experimental groups of six animals each and underwent laparotomy, sigmoid section and immediate anastomosis. Four groups were operated under normothermia (36 ± 1ºC), and the other four under hypothermia (32 ± 1ºC). The animals were reoperated on days 3, 7 and 14 postoperatively, and two groups underwent SHAM at 3 days. From the scar tissue samples, the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was evaluated, and the levels of non-enzymatic markers of oxidative stress, such as reduced glutathione (GSH) and lipid peroxidation, were measured by the thiobarbituric acid reactive substances (TBARS) assay. The means were compared between groups corresponding to each day of sampling and euthanasia. RESULTS: The hypothermic groups showed a significant reduction on the activity of SOD on day 7 postoperatively, on the activity of CAT on days 7 and 14 postoperatively and on the levels of GSH on day 7 postoperatively. The level of lipid peroxidation was increased in the hypothermia group on day 7 postoperatively and decreased on day 14 compared with the normothermic groups. CONCLUSION: Perioperative hypothermia reduced the activity of the antioxidant enzymes catalase and superoxide dismutase, glutathione levels and increased lipid peroxidation in the scar tissue of colonic anastomoses in rats. .

Animals , Male , Colon/surgery , Hypothermia, Induced/adverse effects , Reactive Oxygen Species/metabolism , Wound Healing/physiology , Anastomosis, Surgical , Catalase/metabolism , Colon/enzymology , Glutathione/metabolism , Lipid Peroxidation , Oxidation-Reduction , Oxidative Stress/physiology , Postoperative Period , Random Allocation , Rats, Wistar , Superoxide Dismutase/metabolism , Time Factors
Salud pública Méx ; 56(5): 431-439, sep.-oct. 2014. ilus, tab
Article in English | LILACS | ID: lil-733316


Objective. To describe the incidence, mortality, time trends and prognostic factors for cervical cancer in Cali, Colombia, and to review the molecular epidemiological evidence showing that HPV is the major and necessary cause of cervical cancer and the implications of this discovery for primary and secondary prevention. Materials and methods. Incidence rates of cervical cancer during a 45-year period (1962-2007) were estimated based on the population-based cancer registry of Cali and the mortality statistics from the Municipal Health Secretariat of Cali. Prognostic factors were estimated based on relative survival. Review of the molecular epidemiological evidence linking HPV to cervical cancer was focused on the studies carried out in Cali and in other countries. Results. Incidence rates of squamous cell carcinoma (SCC) declined from 120.4 per 100 000 in 1962-1966 to 25.7 in 2003-2007 while those of adenocarcinoma increased from 4.2 to 5.8. Mortality rates for cervical cancer declined from 18.5 in 1984-1988 to 7.0 per 100 000 in 2009-2011. Survival was lower in women over 65 years of age and in clinical stages 3-4. Review of the molecular epidemiological evidence showed that certain types of HPV are the central and necessary cause of cervical cancer. Conclusions. A decline in the incidence and mortality of SCC and an increase in the incidence of adenocarcinoma during a 45-year period was documented in Cali, Colombia.

Objetivos. Describir la tendencia temporal de la incidencia, mortalidad y los factores pronósticos del cáncer de cuello uterino en Cali, Colombia, y revisar la evidencia epidemiológica molecular que muestra que el VPH es la causa principal y necesaria del cáncer cervical y las implicaciones de este descubrimiento para la prevención primaria y secundaria. Material y métodos. Se estimaron las tasas de incidencia de cáncer de cuello uterino durante un periodo de 45 años (1962-2007) con la información del registro poblacional de cáncer de Cali y las de mortalidad con las estadísticas de la Secretaría de Salud Municipal de Cali. Los factores pronósticos se estimaron sobre la base de la supervivencia relativa. La revisión de la evidencia epidemiológica molecular que une el VPH con el cáncer cervical se centró en los estudios llevados a cabo en Cali y en otros países. Resultados. Las tasas de incidencia de carcinoma de células escamosas (SCC) por 100000 se redujeron desde 120.4 en 1962-66 a 25.7 en 2003-07, mientras que las de adenocarcinoma aumentaron desde 4.2 hasta 5.8. Las tasas de mortalidad por cáncer de cuello uterino por 100000 se redujeron desde 18.5 en 1984-88 a 7.0 en 2009-11. La supervivencia fue menor en las mujeres de más de 65 años de edad y en los estadios clínicos 3-4. La revisión de la evidencia epidemiológica molecular mostró que ciertos tipos de VPH son la causa central y necesaria del cáncer cervical. Conclusiones. Se documentó la disminución de la incidencia y la mortalidad por SCC y un aumento en la incidencia de adenocarcinoma durante un periodo de 45 años en Cali, Colombia.

Animals , Male , Mice , Rats , Butadienes/pharmacokinetics , Carcinogens/pharmacokinetics , Epoxy Compounds/pharmacokinetics , Administration, Inhalation , Butadienes/administration & dosage , Butadienes/toxicity , Glutathione/metabolism , Rats, Sprague-Dawley , Species Specificity
Salud pública Méx ; 56(5): 448-456, sep.-oct. 2014. ilus, tab
Article in English | LILACS | ID: lil-733318


Objective. To describe the behavior of breast cancer (BC)during the 1962-2012 period from information provided by the Cali Cancer Registry and the Municipal Health Secretariat of Cali. Materials and methods. The incidence trend (1962-2007) and mortality trend (1984-2012) for breast cancer was studied and relative survival (RS)(1995-2004) was estimated. Age-standardized incidence and mortality rates to the world population (ASIR(w)/ASMR(w)) were expressed per 100000 persons-year. Their temporal trend was examined with the annual percent of change (APC), and the Cox model was used to analyze the variables that influenced the survival of women with breast cancer. Results. The risk of breast cancer significantly increased in Cali through the 1962-2007 period, with an APC =1.7(95%CI:1.4-2.0). The ASIR(w) of BC increased from 27.1 in 1962 to 48.0 in 2007 and currently there are more than 500 cases reported annually. The mortality for BC has remained stable since 1984; in the 2009-2012 period, the ASMR(w) was 14.2. The 5-year RS was 69% (95%CI:66-71) from 2000-2004 and 62% (95%CI:59-65) from 1995-1999. The risk of death (HR) from BC was greater in persons from lower socioeconomic strata (SES) than from higher SES, HR=1.9(95%CI:1.3-2.9) and in those older than 70 years vs. <50, HR=1.6(95%CI:1.1-2.2). Conclusion. Mortality remained stable while incidence increased and survival improved, which may be associated with better detection and advances in treatment.

Objetivo. Describir el comportamiento del cáncer de mama (CaMa) entre 1962 y 2012 con la información del Registro Poblacional de Cáncer de Cali y de la Secretaría de Salud Municipal de Cali, Colombia. Material y métodos. Se estudió la tendencia de la incidencia (1962-2007) y mortalidad (1984-2012) por CaMa y se estimó la supervivencia relativa (SR) (1995-2004). Las tasas de incidencia y mortalidad estandarizadas por edad con población estándar mundial (TIEE(m)/TMEE(m)) se expresan por 100000 personas/año. Su tendencia temporal fue estudiada con el porcentaje de cambio anual (APC, por su sigla en inglés) y el modelo de Cox fue utilizado para analizar las variables que influyen en la supervivencia. Resultados. La TIEE(m) de CaMa aumentó de 27.1 en 1962 a 48.0 en 2007 y actualmente más de 500 casos son registrados anualmente, con un APC de 1.7(IC95%:1.4-2.0). La mortalidad por CaMa ha permanecido estable desde 1984; en el periodo 2009-2012 la TMEE(m) fue 14.2. La SR a cinco años fue 69% (IC95%:66-71) durante el periodo 2000-2004 y 62% (IC95%: 59-65) entre 1995 y 1999. El riesgo de morir (HR, por su sigla en inglés) por CaMa fue mayor en las personas de estratos socioeconómicos (ESE) bajos vs ESE altos, HR=1.9(IC95%:1.3-2.9) y en los mayores de 70 años vs los menores de 50, HR=1.6(95%CI:1.1-2.2). Conclusión. La mortalidad estable, con aumento de la incidencia y mejor supervivencia, puede estar asociada con una mejor detección y avances en el tratamiento.

Animals , Mice , Rats , Carcinogens/pharmacokinetics , Epoxy Compounds/pharmacokinetics , Models, Biological , Glutathione/metabolism
Salud pública Méx ; 56(5): 429-501, sep.-oct. 2014. ilus, tab
Article in English | LILACS | ID: lil-733322


Objective. To compare the costs and number of undetected cases of four cervical cancer screening strategies (CCSS) in Mexico. Materials and methods. We estimated the costs and outcomes of the following CCSS: a) conventional Papanicolaou smear (Pap) alone; b) high-risk human papilloma virus testing (HR-HPV) as primary screening with Pap as reflex triage; c) HR-HPV as primary screening with HPV-16/18 typing, liquid-based cytology (LBC) and immunostaining for p16/Ki67 testing as reflex triage, and d) co-testing with HR-HPV and LBC with HPV-16/18 typing and immunostaining for p16/Ki67 as reflex triage. The outcome of interest was high-grade cervical lesions or cervical cancer. Results. HR-HPV testing, HPV typing, LBC testing and immunostaining is the best alternative because it is the least expensive option with an acceptable number of missed cases. Conclusions. The opportunity costs of a poor quality CCSS is many false negatives. Combining multiple tests may be a more cost-effective way to screen for cervical cancer in Mexico.

Objetivo. Comparar los costos y los casos no detectados de cuatro estrategias de tamizaje de cáncer cervical (ETCC) en México. Material y métodos. Se estimaron los costos y resultados en salud de las siguientes ETCC: a) citología convencional como único procedimiento de tamizaje; b) detección de virus del papiloma humano de alto riesgo (VPH-AR) como tamizaje primario y citología convencional como procedimiento de triage; c) detección de VPH-AR como tamizaje primario y tipificación de VPH-16/18, citología en base líquida e inmunotinción para p16/Ki67 como procedimientos de triage, y d) evaluación conjunta con VPH-AR y citología en base líquida como tamizaje primario y tipificación de VPH-16/18 e inmunotinción para p16/Ki67 como procedimientos de triage. El resultado en salud analizado fueron los casos de neoplasia intraepitelial cervical (CIN 2/3) o cáncer cervical detectados. Resultados. La ETCC basada en la detección de VPH-AR como prueba primaria y seguida de la tipificación de VPH-16/18, la citología en base líquida y la inmunotinción para p16/Ki67 como procedimientos de triage es la mejor alternativa, ya que es la menos costosa y la que tuvo un nivel aceptable de casos perdidos. Conclusiones. El costo de oportunidad de una ETCC de mala calidad es un alto número de falsos negativos. La combinación seriada de varias pruebas de tamizaje y triage puede ser una alternativa costo-efectiva para la detección oportuna de cáncer cervical en México.

Animals , Female , Humans , Male , Mice , Rats , Butadienes/pharmacokinetics , Carcinogens/pharmacokinetics , Epoxy Compounds/blood , Glutathione/metabolism , Hemoglobins/metabolism , Body Burden , Butadienes/toxicity , Models, Biological , Rats, Sprague-Dawley , Rats, Wistar , Species Specificity
J. pediatr. (Rio J.) ; 90(5): 493-499, Sep-Oct/2014. graf
Article in English | LILACS | ID: lil-723171


Objective: To explore the effect of erythromycin on hyperoxia-induced lung injury. Methods: One-day-old preterm offspring Sprague-Dawley (SD) rats were randomly divided into four groups: group 1, air + sodium chloride; group 2, air + erythromycin;group 3, hyperoxia + sodium chloride; and group 4, hyperoxia + erythromycin. At one, seven, and 14 days of exposure, glutathione (GSH) and interleukin-1 beta (IL-1 beta) were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and bicinchoninic acid (BCA) was used to detect GSH protein. γ-glutamine-cysteine synthetase (γ-GCS) mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results: Compared with group 1, expressions of GSH and γ-GCS mRNA in group 3 were significantly increased at one and seven days of exposure (p < 0.05), but expression of γ-GCS mRNA was significantly reduced at 14 days; expression of IL-1 beta in group 3 was significantly increased at seven days of exposure (p < 0.05), and was significantly reduced at 14 days. Compared with group 3, expressions of GSH and γ-GCS mRNA in group 4 were significantly increased at one, seven, and 14 days of exposure (p < 0.05), but expressions of GSH showed a downward trend at 14 days; expression of IL-1 beta in group 4 was significantly reduced at one and seven days of exposure (p < 0.05). Conclusions: Changes in oxidant-mediated IL-1 beta and GSH are involved in the development of hyperoxia-induced lung injury. Erythromycin may up-regulate the activity of γ-GCS, increasing the expression of GSH, inhibiting the levels of oxidant-mediated IL-1 beta and alleviating hyperoxia-induced lung injury via an antioxidant effect. .

Objetivo: Explorar o efeito da eritromicina sobre lesões pulmonares induzidas por hiperóxia. Métodos: Uma prole de ratos Sprague-Dawley (SD) prematuros com um dia de vida foi dividida aleatoriamente em quatro grupos: grupo 1 ar + cloreto de sódio, grupo 2 ar + eritromicina, grupo 3 hiperóxia + cloreto de sódio e grupo 4 hiperóxia + eritromicina. Com um, sete e 14 dias de exposição, foram detectadas Glutationa (GSH) e Interleucina-1 beta (IL-1 beta) pelo ensaio imunossorvente ligado à enzima (ELISA), e o ácido bicinconinico (BCA) foi utilizado para detectar a proteína GSH. O mRNA da γ-glutamil-cisteina-sintetase (γ-GCS) foi detectado por reação em cadeia da polimerase via transcriptase reversa (RT-PCR). Resultados: Comparadas ao grupo 1, as expressões do mRNA da GSH e da γ-GCS no grupo 3 aumentaram significativamente com um e sete dias de exposição (p < 0,05), porém a expressão de mRNA da γ-GCS diminuiu significativamente aos 14 dias; a expressão de IL-1 beta no grupo 3 aumentou significativamente aos 7 dias de exposição (p < 0,05) e diminuiu significativamente aos 14 dias. Comparadas ao grupo 3, as expressões do mRNA da GSH e da γ-GCS no grupo 4 aumentaram significativamente com um, sete e 14 dias de exposição (p < 0,05), porém as expressões de GSH mostraram uma tendência de queda aos 14 dias; a expressão de IL-1 beta no grupo 4 foi reduzida significativamente com um e sete dias de exposição (p < 0,05). Conclusões: As variações de IL-1 beta e GSH mediadas por oxidantes estão envolvidas no desenvolvimento de lesão pulmonar induzida por hiperóxia. A eritromicina poderá regular positivamente a atividade da γ-GCS, aumentando a expressão de GSH, inibindo os níveis de interleucina-1beta mediada por ...

Animals , Female , Male , Erythromycin/pharmacology , Glutamate-Cysteine Ligase/drug effects , Hyperoxia/metabolism , Interleukin-1beta/drug effects , Lung/drug effects , Protein Synthesis Inhibitors/pharmacology , Animals, Newborn , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Glutathione/metabolism , Interleukin-1beta/metabolism , Lung Injury/metabolism , Oxygen/metabolism , Oxygen/pharmacology , Protein Synthesis Inhibitors/metabolism , Random Allocation , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction