Campsiandra laurifolia reduces oxidative stress and Iiflammation in rats with ulcerative colitis

Ulcerative colitis (UC) affects the mucosa and submucosa of the large intestine. One of the mechanisms involved in its etiology is oxidative stress (OS), directly involved in the inflammatory process characteristic of UC. The Campsiandra laurifolia, known as acapurana, was described as possessing antioxidant properties. We used 24 male Wistar rats, divided into control (CO), control + acapurana (CO + A), colitis (CL), and colitis + acapurana (CL + A) groups. This study performed histological analysis, measuring anal sphincter pressure (ASP) and lipoperoxidation (LPO). The activity of the antioxidant enzyme superoxide dismutase (SOD) and glutathione (GSH) levels were evaluated. The expression of the nuclear factor kappa B (NFkB) and inducible nitric oxide synthase (iNOS) was analyzed by immunohistochemistry. The statistical analysis used was the one-way analysis of variance (ANOVA), followed by the Student-Newman-Keuls test; values were expressed as mean ± standard error, and the significance level was p < 0.05. In the animals of the CL group, we observed the destruction of the crypts and the presence of mucosal ulcers, edema, and submucosal inflammatory infiltrate, as well as increased damage to the intestinal mucosa, reduced ASP, increased LPO and SOD activity, reduced GSH levels, and increased expression of NFkB and iNOS. The administration of C. laurifolia in the CL + A group was shown to cause regeneration of crypts, reduction of inflammatory infiltrate, reduction of damage to the intestinal mucosa, increase in ASP, and reduction in LPO with the restoration of SOD activity and GSH levels. The immunohistochemistry of NFkB and iNOS was significantly reduced. Therefore, the C. laurifolia aqueous extract appears to exert an antioxidant and anti-inflammatory effect in rats with AA-induced colitis. (AU)

The relieving effect of sun-dried protein tonic on sports fatigue / O efeito calmante na fadiga esportiva da proteína tônica secada ao sol / El efecto calmante en la fatiga deportiva de la proteína tónica secada al sol

ABSTRACT Fatigue is a comprehensive process that involves many physiological and biochemical factors. It is a normal physiological reaction when human physical or mental activities reach a certain level. In recent years, it has been verified that free radicals are closely related to exercise-induced fatigue. Cardamine bursa purified selenoprotein has good oxygen-free radical scavenging ability and anti-lipid peroxide. It could protect mitochondria, liver, and red blood cells from peroxide injury. Therefore, it was speculated that the purification of selenoprotein Cardamine may play an active role in attenuating exercise-induced fatigue by scavenging free radicals. This study cleared the selenite protein Capsella bursa (SPC) as a research object, and evaluated its structural characteristics in relieving exercise-induced fatigue. The selenoprotein index system for exercise-induced fatigue was constructed by combining two AHP methods, principal component analysis and factor analysis. Purity, subunit composition, amino acid composition and RCM content were evaluated. The corresponding RCM protein was preliminarily predicted. The results showed that SPCH could significantly prolong the swimming time (P <0.01), improve the lactate clearance capacity (P <0.01), increase the glycogen content of the liver (P <0.01), and reduce the level of the BUN (P <0.05). SPCH has a good effect in relieving exercise-induced fatigue in mice, so it can be considered for development as a nutritional supplement to alleviate exercise-induced fatigue.

RESUMO Fadiga é um processo abrangente envolvendo muitos fatores fisiológicos e bioquímicos. É uma reação fisiológica normal quando as atividades físicas ou mentais humanas atingem um certo nível. Nos últimos anos, verificou-se que os radicais livres estão intimamente relacionados com a fadiga induzida pelo exercício. A selenoproteina purificada de Cardamina bursa tem boa capacidade de depuração de radicais sem oxigénio e de peróxido anti-lípido. Poderia proteger as mitocôndrias, fígado e glóbulos vermelhos de lesões por peróxido. Por conseguinte, especulou-se que a purificação da selenoproteina de Cardamina pode desempenhar um papel activo na atenuação da fadiga induzida pelo exercício por meio de radicais livres de scavenging. Este estudo depurou a proteína selenita Capsella bursa (SPC) como objeto de pesquisa, e avaliou as suas características estruturais no alívio da fadiga induzida pelo exercício. O sistema de índice de selenoproteinas para a fadiga induzida pelo exercício foi construído por meio da combinação dos métodos de AHP, análise principal de componentes e a análise de fatores. Foram avaliados a pureza, a composição sub-unitária, a composição de aminoácidos e o conteúdo do RCM. A proteína correspondente do RCM foi prevista preliminarmente. Os resultados mostraram que o SPCH poderia prolongar significativamente o tempo de natação (P < 0.01), melhorar a capacidade de depuração do lactato (P< 0.01), aumentar o conteúdo do glicogênio do fígado (P < 0.01), e reduzir o nível do BUN (P< 0.05). o SPCH tem um bom efeito em aliviar a fadiga induzida pelo exercício em ratos, de modo que pode ser considerado para desenvolvê-lo como um suplemento nutricional para aliviar a fadiga induzida pelo exercício.

RESUMEN La fatiga es un proceso abarcador que envuelve muchos factores fisiológicos y bioquímicos. Es una reacción fisiológica normal cuando las actividades físicas o mentales humanas alcanzan un cierto nivel. En los últimos anos, se verificó que los radicales libres están íntimamente relacionados con la fatiga inducida por el ejercicio. La selenoproteína purificada de Cardamina bursa tiene buena capacidad de depuración de radicales sin oxígeno y de peróxido antilipídico. Podría proteger las mitocondrias, el hígado y los glóbulos rojos de lesiones por peróxido. Por consiguiente, se especuló que la purificación de la selenoproteína de Cardamina puede desempeñar un papel activo en la atenuación de la fatiga inducida por el ejercicio por medio de radicales libres de scavenging. Este estudio depuró la proteína selenita Capsella bursa (SPC) como objeto de investigación, y evaluó sus características estructurales en el alivio de la fatiga inducida por el ejercicio. El sistema de índice de selenoproteínas para a fatiga inducida por el ejercicio fue construido por medio de la combinación dos métodos de AHP, el análisis principal de componentes y el análisis de factores. Fueron evaluados la pureza, la composición sub-unitaria, la composición de aminoácidos y el contenido del RCM. La proteína correspondiente del RCM fue prevista preliminarmente. Los resultados mostraron que el SPCH podría prolongar significativamente el tiempo de natación (P < 0.01), mejorar la capacidad de depuración del lactato (P< 0.01), aumentar el contenido del glicógeno del hígado (P < 0.01), y reducir el nivel del BUN (P< 0.05). el SPCH tiene un buen efecto en aliviar la fatiga inducida por el ejercicio en ratones, de modo que puede ser considerado para desarrollarlo como un suplemento nutricional para aliviar la fatiga inducida por el ejercicio.

Aging and low-intensity exercise change oxidative biomarkers in brain regions and radiographic measures of femur of Wistar rats

We investigated changes in oxidative biomarkers in brain regions such as brainstem, cerebellum, and cerebral cortex of 3-, 6-, 18-, 24-, and 30-month-old rats. We also assessed the effects of low-intensity exercise on these biomarkers in these regions of 6-, 18-, and 24-month-old rats that started exercise on a treadmill at 3, 15, and 21 months of age, respectively. Radiographic images of the femur were taken for all rats. A total of 25 rats (age: twelve 6-, ten 18-, ten 24-, and three 30-month-old rats) were used. Lipid hydroperoxide levels increased in cerebellum at 18 months. Total antioxidant activity exhibited lowest values in brainstem at 3 months. Superoxide dismutase activity did not exhibit significant changes during aging. Total thiol content exhibited lowest values in brain regions of 24- and 30-month-old rats. Exercise reduced total thiol content in brainstem at 6 months, but no change occurred in other regions and other ages. Femur increased its length and width and cortical thickness with advancing age. No change occurred in medullary width. Radiolucency increased and sclerosis was found in cortical and medullary bone with advancing age. Exercise reduced radiolucency and medullary sclerosis. Therefore, aging differentially changed oxidative biomarkers in different brain regions and radiographic measures of the femur. Low-intensity exercise only ameliorated some radiographic measurements of femur. Since the present study possessed limitations (small number of rats per group), a beneficial effect of regular low-intensity exercise on oxidative markers in brain cannot be ruled out.

Marcadores de estrés oxidativo en pacientes con esclerosis múltiple durante un brote y su remisión / Oxidative stress markers in patients with multiple sclerosis during an outbreak and its remission / Marcadores de estresse oxidativo em pacientes com esclerose múltipla durante um surto e sua remissão

La esclerosis múltiple remitente-recurrente (EM-RR) es una enfermedad desmielinizante del sistema nervioso central. A fin de entender la asociación del estrés oxidativo a nivel periférico con la recaída de la enfermedad se determinaron los niveles de marcadores de estrés oxidativo en plasma de pacientes en la recaída o brote y una semana después de la misma. Se analizaron muestras de 60 personas (20 pacientes con recaída, 20 pacientes sin recaída y 20 controles sanos). Se cuantificaron mediante métodos espectrofotométricos las actividades enzimáticas de óxido nítrico sintasa (ONS), glutatión peroxidasa (GPx), los niveles de lipoperóxidos y nitritos-nitratos y la fluidez de membrana. En el brote de la enfermedad aumentan significativamente los niveles de las actividades enzimáticas de ONS y GPx y los niveles de nitritos-nitratos y lipoperóxidos (p<0,01 en todos los casos), al ser comparados con los de individuos sanos. Dichos parámetros disminuyeron significativamente una semana después de iniciado el brote. Además, los parámetros evaluados se mantuvieron elevados en pacientes que no experimentaron un brote de la enfermedad cuando se los comparó con individuos sanos. La fluidez de membrana en los pacientes con y sin brote fue similar a la de los controles. En conclusión, el estrés oxidativo es un componente importante en los pacientes con esclerosis múltiple.

Recurrent-remitting multiple sclerosis (RR-MS) is a demyelinating disease of the central nervous system. In order to understand the association of oxidative stress at the peripheral level with the relapse of the disease, the levels of oxidative stress markers in plasma of patients in the relapse or outbreak and one week after relapse were determined. Samples of 60 subjects were analyzed (20 patients in relapse, 20 patients without relapse, and 20 healthy controls). The enzymatic activities of nitric oxide synthase (NOS), glutathione peroxidase (GPx), lipoperoxides and nitrite-nitrate levels and membrane fluidity were quantified by spectrophotometric methods. In relapse, the levels of enzymatic activities of NOS and GPx, and the levels of lipoperoxides and nitrites-nitrates were significantly increased (p<0.01, in all cases), compared with healthy individuals. These parameters decreased significantly 1 week after the start of the outbreak. In addition, the parameters evaluated remained high in patients who did not experience an outbreak of the disease compared to healthy subjects. The membrane fluidity in the patients with and without outbreak was similar to that of the controls. In conclusion, oxidative stress is an important component in patients with multiple sclerosis.

A esclerose múltipla recorrente-remitente (EM-RR) é uma doença desmielinizante do sistema nervoso central. Para compreender a associação do estresse oxidativo a nível periférico com a recaída da doença foram determinados os níveis de marcadores de estresse oxidativo em plasma de doentes na recaída ou surto e uma semana após a recaída. Foram analisadas a amostras de 60 pessoas (20 pacientes com recaída, 20 pacientes sem recaída e 20 controles saudáveis). As atividades enzimáticas de óxido nítrico sintase (ONS), glutationa peroxidase (GPX), os níveis de lipoperóxidos e nitritos-nitratos e a fluidez de membrana foram quantificadas por métodos espectrofotométricos. No surto da doença aumentam em forma significativa os níveis da atividade enzimática de ONS e GPX, e os níveis de nitritos-nitratos e lipoperóxidos (p<0,01 em todos os casos), em comparação com os indivíduos saudáveis. Esses parâmetros diminuíram significativamente uma semana após o início do surto. Além disso, os parâmetros avaliados permaneceram elevados em pacientes que não experimentaram um surto da doença quando comparados com indivíduos saudáveis. A fluência de membrana nos pacientes com e sem surto foi semelhante à dos controles. Em conclusão, o estresse oxidativo é um componente importante nos pacientes com esclerose múltipla.

Avaliação de propriedades funcionais e oxidação lipídica em mortadela com aplicação de maca peruana / Evaluation of functional properties and lipid oxidation in mortadella with application of maca peruana

Avaliou-se durante 90 dias o pH, a cor, a capacidade de retenção de água (CRA), a textura e a oxidação lipídica, de uma formulação de mortadela otimizada por meio de um delineamento experimental de mistura para dois componentes. Desenvolveram-se duas amostras da formulação de mortadela otimizada, com antioxidante (OA) e sem antioxidante (OS). Os valores de pH e CRA não apresentaram diferenças significativas ao final dos 90 dias entre as amostras, OA (6,02 e 94,05 g/100g) e OS (6,07 e 93,25 g/100g). Na cor houve diferenças significativas. Na textura, apenas a dureza, mastigabilidade e coesividade apresentaram diferenças significativas. E aos 90 dias as amostras com (2,10 mg de MDA/Kg) e sem antioxidante (2,59 mg de MDA/Kg) não apresentaram diferenças significativas para oxidação lipídica e podem ser considerados aceitáveis para produtos cárneos.

Efeito da adição de óleo essencial de Origanum vulgar e Ocimum gratissimum L. no perfil lipídico da gordura de palma usada em fritura de batata tipo chips / Palm oil fatty acid profile evaluation during the potato chips processing with Origanum vulgar and Ocimum gratissimum L

O objetivo deste trabalho foi avaliar o efeito antioxidante dos óleos essenciais de orégano e alfavacão sobre a estabilidade e perfil de ácidos graxos da gordura de palma utilizada no processamento industrial. Foram adicionados 100ug.g-1 de óleos essenciais em gordura de palma, que foi submetida a onze ciclos de fritura de batatas tipo chips. Amostras da gordura submetidas ao processamento foram analisadas quanto às características físico-químicas e perfil de ácidos graxos. Nas condições do estudo, não foi observado efeito dos óleos essenciais sobre a inibição na formação de compostos trans. Não houve alteração da relação de ácidos graxos poli-insaturados e ácidos graxos saturados da gordura. No entanto, a análise de peróxido indicou um efeito positivo do óleo essencial de alfavacão na redução da formação de radicais livres.

Aumento de estresse oxidativo no sangue de pacientes com ostomia / Increased oxidative stress in the blood of ostomy patients

ABSTRACT BACKGROUND: Ostomy is a surgical procedure that creates a stoma that aims to construct a new path for the output of feces or urine. The relationship of oxidative stress (OxS) markers in patients with ostomy is still poorly described. OBJECTIVE: The present study was aimed at investigating the changes in oxidative stress parameters in peripheral blood collected from ostomy patients when compared with a healthy control group. METHODS: It was evaluated 29 ostomy patients and 30 healthy control patients. The oxidative stress parameters evaluated were: lipid peroxidation [lipid hydroperoxide (LPO), 8-isoprostane (8-ISO) and 4-hydroxynonenal (4-HNE)], protein oxidation and nitration [carbonyl and 3-nitrotyrosine (3-NT)] and DNA oxidation [8-hydroxy-2'-deoxyguanosine (8-OHDG)] in serum from ostomy patients compared to health controls. RESULTS: The data showed an increase of LPO, 8-ISO, 4-HNE, 3-NT and 8-OHDG in serum collected from ostomy patients when compared to healthy controls. CONCLUSION: The findings support the hypothesis that ostomy triggers the oxidative stress observed in the blood collected from these patients.

RESUMO CONTEXTO: Ostomia é um procedimento cirúrgico que cria um estoma com objetivo de construir um novo caminho para a saída das fezes ou urina. A relação dos marcadores de estresse oxidativo em pacientes ostomizados ainda é pouco descrita. OBJETIVO: O presente estudo tem como objetivo investigar as alterações dos parâmetros de estresse oxidativo em sangue de pacientes ostomizados comparados a controles saudáveis. MÉTODOS: Foram avaliados 29 pacientes ostomizados e 30 controles saudáveis. Os parâmetros de estresse oxidativo avaliados foram: peroxidação lipídica [hidroperóxido de lipídio (LPO), 8-isoprostano (8-ISO) e 4-hidroxinonenal (4-HNE)], oxidação e nitração de proteínas [carbonila e 3-nitrotirosina (3-NT)] e oxidação do DNA [8-hidroxi-2'-desoxiguanosina (8-OHDG)] em soro de pacientes ostomizados comparados a controles saudáveis. RESULTADOS: Os dados mostraram um aumento de LPO, 8-ISO, 4-HNE, 3-NT e 8-OHDG em soro de pacientes ostomizados em comparação a controles saudáveis. CONCLUSÃO: Os achados sustentam a hipótese de que a ostomia desencadeia o estresse oxidativo observado no sangue coletado destes pacientes.

Use of aqueous extract of noni in extender for sheep semen freezing / Utilização do extrato aquoso de noni em diluente para congelação de sêmen ovino

The study aimed to evaluate the action of aqueous extract of noni in an extender for sheep semen freezing. Treatments differed in inclusion of aqueous extract of noni in the extender: T1 ˗ no addition; T2 ˗ 24µg/mL; T3 ˗ 72µg/mL; and T4 ˗ 120µg/mL. Ejaculates were collected, diluted in the four treatments, and frozen. After thawing, the semen was subjected to a thermoresistance test and evaluated for subjective motility, vigor, membrane integrity assessment by hypo-osmotic swelling test, live-dead assay, computer-assisted sperm analysis and the status of sperm capacitation and acrosome reaction. Data were subjected to ANOVA, and then to Student Newman Keuls's test at 5% significance level. In the thermoresistance test after two hours of incubation, motility in T4 (120µg/mL) was lower than in the other treatments, with no differences in the HoS test in either diluted semen or in the semen evaluated immediately post-thawing, while for the other times, treatments showed similar responses. Regarding the motility parameters, a difference was observed for progressive motility, curvilinear velocity, average path velocity, and amplitude of lateral head displacement. As to the sperm capacitation status, a difference was observed between treatments for the sperm capacitated with intact acrosome.(AU)

Este estudo teve como objetivo avaliar a ação do extrato aquoso de noni em diluente para congelação de sêmen de carneiro. Os tratamentos diferiram quanto à inclusão de extrato aquoso de noni ao meio diluidor em: T1˗ sem adição de extrato; T2˗ 24µg/mL ; T3- 72µg/mL e 120µg/mL. Por meio de vagina artificial, 16 ejaculados foram coletados, diluídos entre os quatro tratamentos e congelados. Após o descongelamento, o sêmen foi submetido ao teste de termorresistência e avaliado quanto à motilidade subjetiva, ao vigor espermático, à integridade de membrana pelo teste hiposmótico, bem como ao teste supravital, à análise de sêmen assistida por computador (CASA) e ao status de capacitação espermática e de reação acrossomal. Os dados foram submetidos a uma análise de variância, seguida pelo teste de Student-Newman-Keuls com 5% de significância. No teste de termorresistência, após duas horas de incubação, a motilidade do T4 (120µg/mL) apresentou-se inferior aos demais tratamentos. Não houve diferença significativa no teste HOS tanto para o sêmen diluído quanto para o sêmen avaliado imediatamente pós-descongelação; para as demais horas, os tratamentos apresentaram comportamento semelhante. Para os parâmetros de cinética, foi observada diferença estatística para motilidade progressiva, velocidade curvilinear, velocidade do percurso médio e amplitude de deslocamento lateral da cabeça. Quanto ao estado de capacitação espermática, observou-se diferença entre os tratamentos para espermatozoide capacitado com acrossomo intacto.(AU)

Effects of N-acetylcysteine on spinal cord oxidative stress biomarkers in rats with neuropathic pain

N-acetylcysteine (NAC) inhibits nociceptive transmission. This effect has been associated partly with its antioxidant properties. However, the effect of NAC on the levels of lipid hydroperoxides (a pro-oxidant marker), content of ascorbic acid (a key antioxidant molecule of nervous tissue) and total antioxidant capacity (TAC) is unknown. Thus, our study assessed these parameters in the lumbosacral spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve, one of the most commonly employed animal models of neuropathic pain. Thirty-six male Wistar rats weighing 200-300 g were equally divided into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve). All rats received intraperitoneal injections of NAC (150 mg·kg−1·day−1) or saline for 1, 3, or 7 days. Rats were killed 1, 3, and 7 days after surgery. NAC treatment prevented the CCI-induced increase in lipid hydroperoxide levels only at day 1, although the amount was higher than that found in naive rats. NAC treatment also prevented the CCI-induced increase in ascorbic acid content, which occurred at days 1, 3, and 7. No significant change was found in TAC with NAC treatment. The changes observed here may be related to the antinociceptive effect of NAC because modulation of oxidative-stress parameters seemed to help normalize the spinal cord oxidative status altered by pain.

Effect of Otostegia persica extract on ischemia/reperfusion induced renal damage in diabetic rats. A biochemical study

ABSTRACT PURPOSE: To evaluate the effect of Otostegia persica (O. persica) extract on renal damage induced by ischemia/reperfusion (I/R) in diabetic rats. METHODS: Forty-eight rats were subjected to right nephrectomy; then, they were allocated into six groups: Sham; Diabetic sham; I/R; Diabetic I/R; I/R+O. persica; Diabetic I/R+O. persica. Diabetes was induced by streptozotocin (200 mg/kg, i.p.). O. persica (300 mg/kg/day, p.o) was administered for 2 weeks. On the 15th day, ischemia was induced in left kidney for 60 min, followed by reperfusion for 24h. Renal functional and biochemical markers were estimated. RESULTS: I/R in both normal and diabetic rats, induced a significant elevation in serum levels of urea and creatinine (p<0.05). Renal I/R induced a significant increase of malondialdehyde, myeloperoxidase and nitric oxide concentrations associated with significant reduction in superoxide dismutase and catalase activities in comparison with the sham group (p<0.05). Diabetic rats that underwent renal I/R exhibited a significant increase in all the studied parameters with a reduction in the antioxidant enzymes as compared to nondiabetic rats (p<0.05). These deleterious effects associated with renal I/R were improved by the treatment with O. persica (p<0.05). CONCLUSION: Otostegia persica pretreatment protected the renal injury from ischemia-reperfusion in diabetic rats.

Poly(ADP-ribose) polymerase 1 contributes to oxidative stress through downregulation of sirtuin 3 during cisplatin nephrotoxicity / 대한해부학회지

Enhanced oxidative stress is a hallmark of cisplatin nephrotoxicity, and inhibition of poly(ADP-ribose) polymerase 1 (PARP1) attenuates oxidative stress during cisplatin nephrotoxicity; however, the precise mechanisms behind its action remain elusive. Here, using an in vitro model of cisplatin-induced injury to human kidney proximal tubular cells, we demonstrated that the protective effect of PARP1 inhibition on oxidative stress is associated with sirtuin 3 (SIRT3) activation. Exposure to 400 µM cisplatin for 8 hours in cells decreased activity and expression of manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase (GPX), and SIRT3, while it increased their lysine acetylation. However, treatment with 1 µM PJ34 hydrochloride, a potent PARP1 inhibitor, restored activity and/or expression in those antioxidant enzymes, decreased lysine acetylation of those enzymes, and improved SIRT3 expression and activity in the cisplatin-injured cells. Using transfection with SIRT3 double nickase plasmids, SIRT3-deficient cells given cisplatin did not show the ameliorable effect of PARP1 inhibition on lysine acetylation and activity of antioxidant enzymes, including MnSOD, catalase and GPX. Furthermore, SIRT3 deficiency in cisplatin-injured cells prevented PARP1 inhibition-induced increase in forkhead box O3a transcriptional activity, and upregulation of MnSOD and catalase. Finally, loss of SIRT3 in cisplatin-exposed cells removed the protective effect of PARP1 inhibition against oxidative stress, represented by the concentration of lipid hydroperoxide and 8-hydroxy-2'-deoxyguanosine; and necrotic cell death represented by a percentage of propidium iodide–positively stained cells. Taken together, these results indicate that PARP1 inhibition protects kidney proximal tubular cells against oxidative stress through SIRT3 activation during cisplatin nephrotoxicity.

Cisplatin induces primary necrosis through poly(ADP-ribose) polymerase 1 activation in kidney proximal tubular cells / 대한해부학회지

Treatment with cisplatin for cancer therapy has a major side effect such as nephrotoxicity; however, the role of poly (ADP-ribose) polymerase 1 (PARP1) in necrosis in response to cisplatin nephrotoxicity remains to be defined. Here we report that cisplatin induces primary necrosis through PARP1 activation in kidney proximal tubular cells derived from human, pig and mouse. Treatment with high dose of cisplatin for 4 and 8 hours induced primary necrosis, as represented by the percentage of propidium iodide-positive cells and lactate dehydrogenase release. The primary necrosis was correlated with PARP1 activation during cisplatin injury. Treatment with PJ34, a potent PARP1 inhibitor, at 2 hours after injury attenuated primary necrosis after 8 hours of cisplatin injury as well as PARP1 activation. PARP1 inhibition also reduced the release of lactate dehydrogenase and high mobility group box protein 1 from kidney proximal tubular cells at 8 hours after cisplatin injury. Oxidative stress was increased by treatment with cisplatin for 8 hours as shown by 8-hydroxy-2'-deoxyguanosine and lipid hydroperoxide assays, but PARP1 inhibition at 2 hours after injury reduced the oxidative damage. These data demonstrate that cisplatin-induced PARP1 activation contributes to primary necrosis through oxidative stress in kidney proximal tubular cells, resulting in the induction of cisplatin nephrotoxicity and inflammation.

Efeito do betacaroteno sobre o estresse oxidativo e a expressão de conexina 43 cardíaca / Effect of beta-carotene on oxidative stress and expression of cardiac connexin 43

FUNDAMENTO: Estudos de intervenção mostraram aumento da mortalidade em pacientes que receberam betacaroteno. Contudo, não são conhecidos os mecanismos envolvidos nesse fenômeno. OBJETIVO: Avaliar a influência do betacaroteno sobre o estresse oxidativo e a expressão de conexina 43 em coração de ratos. MÉTODOS: Ratos Wistar, pesando aproximadamente 100 g, foram alocados em dois grupos: Grupo Controle (n = 30), que recebeu a dieta usada de rotina em nosso laboratório, e Grupo Betacaroteno (n = 28), que recebeu betacaroteno (na forma de cristal, adicionado e misturado à dieta) na dose de 500 mg de betacaroteno/kg de dieta. Os animais receberam tratamento até que atingissem entre 200 e 250 g, quando eram sacrificados. Foram coletados sangue, fígado e coração para realização de Western blotting e imunoistoquímica para conexina 43; foram realizados estudos morfométricos, dosagens de betacaroteno por cromatografia líquida de alta eficiência bem como de glutationa reduzida, glutationa oxidada e hidroperóxidos de lipídeos por análises bioquímicas. RESULTADOS: O betacaroteno foi detectado apenas no fígado dos animais do Grupo Betacaroteno (288 ± 94,7 µg/kg). Os níveis de glutationa reduzida/glutationa oxidada foram maiores no fígado e no coração dos animais do Grupo Betacaroteno (fígado - Grupo Controle: 42,60 ± 1,62; fígado - Grupo Betacaroteno: 57,40 ± 5,90; p = 0,04; coração: - Grupo Controle: 117,40 ± 1,01; coração - Grupo Betacaroteno: 121,81 ± 1,32 nmol/mg proteína; p = 0,03). O conteúdo de conexina 43 total foi maior no Grupo Betacaroteno. CONCLUSÃO: O betacaroteno apresentou efeito benéfico, caracterizado pelo aumento da comunicação intercelular e melhora do sistema de defesa antioxidante. Nesse modelo, os mecanismos não explicam a maior mortalidade observada com a suplementação de betacaroteno em estudos clínicos. (Arq Bras Cardiol. 2013; [online].ahead print, PP.0-0).

BACKGROUND: Intervention studies have shown an increased mortality in patients who received beta-carotene. However, the mechanisms involved in this phenomenon are still unknown. OBJECTIVE: Evaluate the influence of beta-carotene on oxidative stress and the expression of connexin 43 in rat hearts. METHODS: Wistar rats, weighing approximately 100 g, were allocated in two groups: Control Group (n=30), that received the diet routinely used in our laboratory, and Beta-Carotene Group (n = 28), which received beta-carotene (in crystal form, added and mixed to the diet) at a dose of 500 mg of beta-carotene/kg of diet. The animals received the treatment until they reached 200-250g, when they were sacrificed. Samples of blood, liver and heart were collected to perform Western blotting and immunohistochemistry for connexin 43; morphometric studies, dosages of beta-carotene by high-performance liquid chromatography as well as reduced glutathione, oxidized glutathione and lipids hydroperoxides were performed by biochemical analysis. RESULTS: Beta-carotene was detected only in the liver of Beta-Carotene Group animals (288 ± 94.7 µg/kg). Levels of reduced/oxidized glutathione were higher in the liver and heart of Beta-Carotene Group animals (liver - Control Group: 42.60 ± 1.62; liver - Beta-Carotene Group: 57.40 ± 5.90; p = 0.04; heart: - Control Group: 117.40 ± 1.01; heart - Beta-Carotene Group: 121.81 ± 1.32 nmol/mg protein; p = 0.03). The content of total connexin 43 was larger in Beta-Carotene Group. CONCLUSION: Beta-carotene demonstrated a positive effect, characterized by the increase of intercellular communication and improvement of anti-oxidizing defense system. In this model, mechanism does not explain the increased mortality rate observed with the beta-carotene supplementation in clinical studies. (Arq Bras Cardiol. 2013; [online].ahead print, PP.0-0).

Análise de correlação do perfil lipídico e dano oxidativo em pacientes diabéticos / Correlation analysis of the lipid profile and oxidative damage in diabetic patients

O diabete mellitus (DM) é uma doença multifatorial que acomete diversos sistemas corporais com complicações teciduais e vasculares. Diversas hipóteses bioquímicas estão implicadas na indução das complicações tardias da diabete, como: radicais livres, rota dos polióis e glicação não enzimática de proteínas. O objetivo do presente estudo foi correlacionar o perfil lipídico e lipoperoxidação em indivíduos diabéticos. Realizou-se uma análise do perfil lipídico de 30 pacientes diabéticos do tipo 2, com uma média de 4 anos da evolução da doença. Analisou-se a concentração sanguínea de glicose, colesterol total, HDLc, LDLc, VLDLc, triglicerídeos, hemoglobina glicada e peroxidação lipídica (TBARS). Encontrou-se uma forte correlação entre a concentração de triglicerídeos, colesterol total e VLDLc com o dano oxidativo e uma fraca correlação com colesterol LDLc e HDLc. A análise dos resultados mostra uma forte correlação da lipoperoxidação lipídica com o perfil lipídico dos pacientes que pode reafirmar a necessidade de monitoramento dos lipídios plasmáticos como forma de prevenir complicações tardias inerentes ao diabete.

Diabete mellitus (DM) is a multifactorial disease that affects several body systems, with vasculacomplications and tissue damage. Several biochemical mechanisms are hypothetically implicated in the induction of the late complications of diabete, such as the action of free radicals, glucose metabolism by the polyol pathway and non-enzymatic glycation of proteins. The aim of this study was to correlate the lipid profile and lipid peroxidation in diabetic subjects. An analysis of the lipid profile of 30 diabetic patients, with an average of 4 years since diagnosis. We analyzed the concentration of glucose, total cholesterol, HDLc, LDLc, VLDLc, triglycerides, glycated hemoglobin and lipid peroxidation (TBARS). Oxidative damage (TBARS) showed a strong correlation with the concentration of triglycerides, total cholesterol and VLDLc, and a weak correlation with LDLc cholesterol and HDLc. The strong correlation found between lipid peroxidation and the lipid profile of these patients reinforces the need to monitor plasma lipids in order to prevent late complications associated with diabete.

Effect of thymoquinone on ethanol and high fat diet induced chronic pancreatitis—a dose response study in rats.

A significant increase in serum lipase, amylase, capase-1 and myeloperoxidase activities, oxidative stress index (OSI), IL-1β and IL-18 was observed in rats receiving ethanol (EtOH) and high fat diet (HFD). Thymoquinone (TQ) supplementation along with EtOH and HFD significantly decreased the levels of serum lipase, amylase, capase-1, myeloperoxidase, OSI and maintained the antioxidant status when compared to untreated EtOH and HFD fed rats. Among the 4 doses, 100 mg of TQ/kg body weight was found to provide optimum protective effect on pancreas against EtOH and HFD induced abnormal changes. Histological observations added more evidence for the anti-inflammatory effect of TQ.

Role of Moringa oleifera in regulation of diabetes-induced oxidative stress

OBJECTIVE@#To evaluate the antioxidant activity of aqueous extract of Moringa oleifera (M. oleifera) young leaves by in vivo as well as in vitro assays.@*METHODS@#In vitro study included estimation of total phenolic, total flavonol, total flavonoid and total antioxidant power (FRAP assay). In addition, in vivo study was done with the identified most effective dose of 200 mg/kg of its lyophilized powder on normal and diabetic rats. Its effect on different oxidative free radical scavenging enzymes,viz, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), lipid peroxide (LPO) contents were measured.@*RESULTS@#Significant increase in activities of SOD, CAT, GST while, a decrease in LPO content was observed. Whereas, total phenolic, flavonoid and flavonol contents in the extract were found to be 120 mg/g of GAE, 40.5 mg/g of QE and 12.12 mg/g of QE, respectively. On the other hand, FRAP assay results of M. oleifera leaves was (85.00 ± 5.00) μM/g of extract powder.@*CONCLUSIONS@#The significant antioxidant activities of M. oleifera leaves from both in vivo as well as in vitro studies suggests that the regular intake of its leaves through diet can protect normal as well as diabetic patients against oxidative damage.

Hepatotoxicity in Rats Treated with Dimethylformamide or Toluene or Both

The effects of toluene in dimethylformamide (DMF)-induced hepatotoxicity were investigated with respect to the induction of cytochrome P-450 (CYP) and the activities of related enzymes. The rats were treated intraperitoneally with the organic solvents in olive oil (Single treatment groups: 450 [D1], 900 [D2], 1,800 [D3] mg DMF, and 346 mg toluene [T] per kg of body weight; Combined treatment groups: D1+T, D2+T, and D3+T) once a day for three days, while the control group received just the olive oil. Each group consisted of 4 rats. The activities of the xenobiotic metabolic enzymes and the hepatic morphology were assessed. The immunoblots indicated that the expression of CYP2E1 was considerably enhanced depending on the dosage of DMF and the CYP2E1 blot densities were significantly increased after treatment with both DMF and toluene, compared to treatment with DMF alone. The activities of glutathione-S-transferase and glutathione peroxidase were either decreased or remained unaltered after treatment with DMF and toluene, whereas the lipid peroxide levels were increased with increasing dosage of DMF and toluene. The liver tissue in the D3 group (1,800 mg/kg of DMF) showed signs of microvacuolation in the central vein region and a large necrotic zone around the central vein, in rats treated with both DMF (1,800 mg/kg) and toluene (D3T). These results suggest that the expression of CYP2E1 is induced by DMF and enhanced by toluene. These changes may have facilitated the accelerated formation of N-methylformamide (NMF) from toluene, and the generated NMF may directly induce liver damage.

Suppression of oxidative stress by grape seed supplementation in rats

Polyphenol-rich grape seeds have a beneficial effect on human health. The present study was performed to investigate the effects of grape seeds on antioxidant activities in rats. Male Sprague-Dawley rats were randomly divided into a control diet group (C), a high-fat diet group (HF), a 5% grape seed-supplemented control diet group (G), and a 5% grape seed-supplemented high-fat diet group (HG). Dietary supplementation with grape seeds reduced serum concentrations of lipid peroxides compared with those in the C and HF groups. The hepatic level of lipid peroxides decreased significantly in the grape seed groups compared with that in the C and HF groups. Superoxide dismutase activity in the G group increased significantly compared with that in the C group. Catalase activity tended to be higher by feeding grape seeds. The grape seed diet increased glutathione peroxidase activity in the C group. Glutathione-S-transferase activity increased significantly in the G group compared with that in the C group. Hepatic content of total glutathione increased significantly in the HG group but decreased significantly in the HF group. The ratio of reduced glutathione and oxidized glutathione increased by feeding the grape seed diet. Total vitamin A concentration was significantly higher in HG group than in other groups. Liver tocopherol content of the G and HG groups was significantly higher than that of the control groups. These results suggest that dietary supplementation with grape seeds is beneficial for suppressing lipid peroxidation in high fat-fed rats.

Infección cutánea por citomegalovirus y radicales libres en el mecanismo patogénico del vitíligo generalizado de inicio reciente / Cytomegalovirus skin infection and free radicals in the initial pathogenic mechanism of early onset generalized vitiligo

Objetivo. Determinar el rol de la infección cutánea por citomegalovirus (CMV) y de los niveles elevados de peroxidación lipídica en piel y sangre, en el mecanismo patogénico del vitíligo generalizado de inicio reciente (VGIR). Material y métodos. Estudio analítico de casos y controles. Los pacientes fueron captados en el Servicio de Dermatología del Hospital Nacional Dos de Mayo (Lima, Perú) y seleccionados de acuerdo a criterios de inclusión/exclusión; luego, pasaron a formar parte de los grupos de investigación: Grupo de estudio: 30 pacientes con diagnóstico de VGIR (1 a 12 meses). Grupo control: 30 sujetos sin lesiones en la piel. Se obtuvo muestras de piel de las lesiones del grupo de estudio y piel sana del grupo control, a las que se les realizó reacción en cadena de la polimerasa (PCR) para CMV y estudio anatomopatológico con latinción de hematoxilina-eosina (HE) e inmunoperoxidasa. Se obtuvo muestras de sangre y piel de ambos grupos a las que se les realizó la cuantificación de peroxidación lipídica, mediante el dosaje del malonildialdehído (MDA). Resultados. El 76.6% de los pacientes con VGIR fueron positivos para genoma de CMV en comparación con el 23,3% del grupo control (p < 0,001). En el examen anatomopatológico realizado con las tinciones HE e inmunohistoquímica no se encontraron casos positivos de infección por CMV en ambos grupos. Los niveles de MDA del grupo de estudio fueron significativamente mayores en los pacientes con VGIR en comparación con el grupo control, tanto en piel (p < 0,001) como en sangre (p < 0,001). Conclusiones. Existe asociación entre la infección cutánea por CMV y el daño mediado por radicales libres constituyen mecanismos importantes en el vitíligo generalizado de inicio reciente.

Aim. To demonstrate skin infection by cytomegalovirus (CMV) and increased serum lipoperoxidation levels in patients with early on set generalized vitiligo. Subjects and methods. Case-control study, implemented since march 2004 until December 2005. Patients were divided into two groups: group A, 30 patients with recent diagnostic of vitiligo; group B, 30 controls without skin lesions. Skin samples were obtained from the patients of both groups; which were assessed bypolymerase chain reaction (PCR) for CMV genome, histopathologic test with hematoxilin-eosin stain and immunoperoxidase. Likewise, blood samples were obtained to determinate radical free levels (1ipoperoxidation). Results. Twenty three patients with vitiligo (76,6%) were positive for CMV genome by PCR test, while 7 controls (23,3%) were positive for CMV genome. Likewise a significant statistically difference for CMV infection in patients with vitiligo versus control group (p < 0,001) was found. The histopathology evaluation was negative for both groups. A significant statistically difference between lipoperoxidation levels inpatients with vitiligo and controls (p < 0,001) was found in skin and blood. Conclusions. There is an association between skin infection by CMV and vitiligo in a select group of patients, which have their systemic oxidant state increased in the first year of the disease.

Chelation therapy with desferrioxamine does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in malaysian Chinese β-thalassaemia major patients / La terapia de quelación con deferoxamina no normaliza los niveles de ferritinaa pero atenúa el daño oxidativo y mejora el nivel antioxidante total en los pacientes sinomalayos que padecen de talasemia β

Beta-thalassaemia major causes severe anaemia and patients with it may be transfusion-dependent for life. Regular blood transfusions cause iron-overload that leads to oxidative damage which can hasten mortality. The objective of this research was to study the oxidant-antioxidant indices in β-thalassaemia major patients at the University of Malaya Medical Centre (UMMC) who were on desferrioxaminechelation or without chelation therapy. Blood was collected from 39 Chinese patients and 20 controls. Plasma and peripheral blood mononuclear cell lysates (PBMC) were extracted and biochemical tests to evaluate oxidative stress were performed. Oxidative stress was evident in these patients as advanced oxidized protein products (AOPP) and lipid hydroperoxides were elevated, whereas glutathione peroxidase activity and the ferric reducing antioxidant power (FRAP) were reduced. The catalase activity in the patients' PBMC was elevated, possibly as a compensatory mechanism for the reduced glutathione peroxidase activity in both red blood cells and PBMC. The lower FRAP and higher AOPP levels in the non-chelated patients compared with the chelated patients were indicative of a lower oxidative stress level in the chelated patients. The ferritin levels in the chelated and non-chelated patients were high and the mean levels of liver enzyme activities in the majority of patients were elevated regardless of chelation therapy. In conclusion, this study indicates that desferrioxamine chelation therapy does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese β-thalassaemia major patients.

La beta-talasemia mayor causa anemia severa, y los pacientes con este padecimiento pueden hacerse dependientes de las transfusiones de sangre por el resto de sus vidas. Las transfusiones regulares de sangre dan lugar a una sobrecarga de hierro que conduce al dano oxidativo, el cual a su vez puede acelerar la mortalidad. El objetivo de esta investigación fue estudiar las tasas de oxidantesantioxidantes en pacientes de beta-talasemia mayor en el Centro Médico de la Universidad de Malaya, tanto aquellos bajo tratamiento de quelación con deferoxamina, como aquellos sin terapia de quelación alguna. Se recogieron muestras de sangre de 39 pacientes chinos y 20 controles. Se extrajeron plasma y lisados de celulas mononucleares perifericas (CMSP), y se realizaron pruebas bioquimicas para evaluar el estrés oxidativo. El estrés oxidativo era evidente en estos pacientes en forma de productos avanzados de oxidación de proteinas (PAOP), y los hidroperoxidos de lipidos eran elevados, en tanto que la actividad de glutatión peroxidasa y el poder reductor ferrico/antioxidante (FRAP) era reducida. La actividad de la catalasa en los pacientes de CMSP era elevada, posiblemente como un mecanismo compensatorio frente a la actividad de glutatión peroxidasa reducida tanto en los globulos rojos como en las CMSP. Los niveles más bajos de FRAP y los más altos de PAOP en los pacientes no quelados en comparación con los pacientes quelados, indicaban un bajo nivel de estrés oxidativo en los pacientes quelados. Los niveles de ferritina tanto en los pacientes quelados como en los no quelados, eran altos, y los niveles promedio de actividades enzimaticas del higado fueron elevados en la mayoria de los pacientes, independientemente de la terapia de quelación. En conclusión, este estudio indica que la terapia de quelación con deferoxamina no normaliza el nivel de ferritina, pero en cambio atenua el daño oxidativo, y mejora el nivel antioxidante total en los pacientes sinomalayos afectados por la betatalasemia mayor.