Aluminum and ethanol induce alterations in superoxide and peroxide handling capacity (SPHC) in frontal and temporal cortex.

Aluminum is an omnipresent neurotoxicant and has been associated with several neuropathological disorders. Cerebrum and cerebellum have been shown to face augmented oxidative stress when animals are exposed to aluminum and high doses of ethanol. To establish the link between oxidative stress and neurobehavioral alterations, the present study was conducted to determine the extent of oxidative stress in low levels of pro-oxidant (ethanol exposure) status of the functionally discrete regions of the cerebrum. Male Wistar rats were exposed to aluminum (10 mg/kg body wt) and ethanol (0.2-0.6 g/kg body wt) for 4 weeks. Spontaneous motor activity (SMA) and Rota-Rod performances (RRP) were recorded weekly during the period of exposure. At the end of 4th week, oxidative stress parameters were determined from the homogenized cerebral tissue. GSH-independent superoxide peroxide handling capacity (GI-SPHC) and GSH-dependent superoxide peroxide handling capacity (GD-SPHC) were determined for FC and TC upon exposure to ethanol in the absence and presence of aluminum exposure. Aluminum was found to augment the oxidative stress at higher doses (0.6 g Ethanol/kg body wt) of ethanol, particularly in FC. The SPHC of FC was also found to be compromised significantly in aluminum-ethanol co-exposed animals. It was concluded that even though the manifestation of oxidative stress was not observed as revealed by assaying the widely used oxidative stress biochemical markers (indices), aluminum and ethanol (low doses) exposure induced alterations in the handling capacity of oxidant imbalance that could be recognized by studying the SPHC of FC. Comparison of GD-SPHC and GI-SPHC offered a possible mechanism of compromised SPHC in FC. This observation is likely to offer insights into the mechanism of association between aluminium exposure and behavioral changes in neurodegenerative disorders towards therapeutic strategies for these disorders.

Effect of aluminum exposure on superoxide and peroxide handling capacities by liver, kidney, testis and temporal cortex in rat.

Oxidant imbalance is one of the causative mechanisms of aluminum-induced neurotoxicity. In this study, we investigated aluminum-induced oxidant imbalance in non-neuronal tissues (liver, kidney and testis) and temporal cortex in rats. The differences in adaptations to superoxide and peroxide handling capacities (SPHC) of studied organs due to aluminum insult were also evaluated. Male Wistar rats were exposed to aluminum (10 mg/Kg body wt/day) for 4 weeks through orogastric intubation. Liver showed significant decrease in reduced glutathione level, while significant alteration in lipid peroxidation was observed in temporal cortex in aluminium-exposed animals. Superoxide dismutase activity was significantly altered in liver and temporal cortex and catalase activity significantly reduced in the liver due to aluminum exposure, while glutathione reductase and glutathione peroxidase activities were altered in all the tested organs. Among the organs, glutathione-independent SPHC was relatively higher in liver and kidney, while glutathione-dependent SPHC was relatively higher in testis and temporal cortex. As compared to control, aluminum-exposed rats demonstrated reduction in glutathione-dependent SPHC in temporal cortex and increment of the same in testis, while increment in glutathione-independent SPHC was observed in liver. In conclusion, aluminum-induced alteration in oxidant handling capacity could be the cause of oxidative stress both in the neuronal and non-neuronal tissues.

A Protective Role for Heme Oxygenase-1 in INS-1 Cells and Rat Islets that are Exposed to High Glucose Conditions

Heme oxygenase-1 (HO-1) has been described as an inducible protein that is capable of cytoprotection via radical scavenging and the prevention of apoptosis. Chronic exposure to hyperglycemia can lead to cellular dysfunction that may become irreversible over time, and this process has been termed glucose toxicity. Yet little is known about the relation between glucose toxicity and HO-1 in the islets. The purposes of the present study were to determine whether prolonged exposure of pancreatic islets to a supraphysiologic glucose concentration disrupts the intracellular balance between reactive oxygen species (ROS) and HO-1, and so this causes defective insulin secretion; we also wanted to evaluate a protective role for HO-1 in pancreatic islets against high glucose levels. The intracellular peroxide levels of the pancreatic islets (INS-1 cell, rat islet) were increased in the high glucose media (30 mM glucose or 50 mM ribose). The HO-1 expression was induced in the INS-1 cells by the high glucose levels. Both the HO-1 expression and glucose stimulated insulin secretion (GSIS) was decreased simultaneously in the islets by treatment of the HO-1 antisense. The HO-1 was upregulated in the INS-1 cells by hemin, an inducer of HO-1. And, HO-1 upregulation induced by hemin reversed the GSIS in the islets at a high glucose condition. These results suggest HO-1 seems to mediate the protective response of pancreatic islets against the oxidative stress that is due to high glucose conditions.

Atopic cataracts in a child with atopic dermatitis: a case report and review of the literature.

Cataracts induced by atopic dermatitis rarely occur in adolescent and young adult patients suffering from this problem. Lenticular opacity is an important ocular complication in atopic dermatitis. Although the cause of atopic dermatitis and its ocular complications are unknown, cataracts have been observed to develop and progress during periods of exacerbation of the dermatitis. We report the case of a 16-year-old boy with atopic dermatitis who abruptly developed cataracts in both eyes while suffering from severe skin itching which began 2 months before the initial examination. His peroxidation test result was very high, and we postulate the retinal peroxidation might play a key role in cataractogenesis. Lens aspiration and intraocular artificial lens implantation were performed smoothly with restoration of visual acuity in both eyes.

Alquilaçäo de DNA por radicais metila gerados a partir de hidroperóxido de tércio-butila: Estudos in vitro e in vivo / DNA alkylation by methyl radical generated from of tert-butyl hydroperoxide: study in vitro and in vivo

Estudamos a possibilidade do hidroperóxido de tércio-butila, um reconhecido agente citotóxico e promotor de tumor, metilar DNA via ataque radicalar. inicialmente realizamos estudos por EPR associada à técnica do captador de spin in vitro para comprovar que o composto é decomposto em radicais metila na presença de DNA. Posteriormente demonstramos que TBHP na presença de Fe (II) alquila DNA de timo bovino pela detecçÝo de 80metilguanina. Detectamos, entretanto, adutos esperados tanto do ataque de espécies radicalares (8-metilguanina), como de espécies catiônicas (7-metilguanina, 3-metiladenina, 6-metilguanina) cuja formaçäo näo seria esperada durante a reduçäo do hidroperóxido de tércio-butila por Fe (II). Em funçäo disto, estudamos a influência de agentes quelantes e do íon metálico (Fe (II), Fe (III) e Cu (I)) no processo de alquilaçäo...

Possible roles of nitric oxide and peroxynitrite in murine leishmaniasis

Activated macrophages simultaneously synthesize nitric oxide and superoxide anion which can react with each other producing peroxynitrite. Consequently, it has been difficult to assess the precise contribution of each of the formed reactive oxygen- and nitrogenderived species to the microbicidal activities of macrophages, particularly in vivo. To explore this problem, we are examining the formation and potential roles of nitrogen-derived intermediates in Leishmania amazonensis murine infection. Thus far, our results have demonstrated that peroxynitrite is a potent leishmanicidal agent in vitro and that both nitric oxide and peroxynitrite are formed during infection of susceptible BALB/c mouse strain. Nitric oxide was detected as the nitrosyl-hemoglobin complex by electron paramagnetic resonance analysis of blood drawn from mice at different times of infection, and it was shown to increase with the evolution of the disease. These results will be discussed in the context of the dual physiological role of nitric oxide either as a signaling molecule or as a deleterious agent.

Peroxidative changes in experimental diabetes mellitus.

Changes in the levels of lipid peroxides and antioxidant enzymes were studied in male albino rats with experimental diabetes mellitus. Diabetes was induced by single subcutaneous injection of alloxan (19 mg/100 g body weight). The concentration of malondialdehyde (MDA) showed an increase both in the liver (P less than 0.01) and kidney (0 less than 0.05), while in the heart, there was a decrease (P less than 0.01), as compared to control values. A similar pattern of change was observed in the level of hydroperoxides in the liver and heart. The conjugated dienes showed an elevation during diabetes in all tissues (P less than 0.01). Glutathione levels in heart (P less than 0.01) and kidney were found to be decreased (P less than 0.05) while the liver showed an elevation during long-term diabetes (P less than 0.01). Serum ceruloplasmin showed an increase (P less than 0.05) in diabetes. Antioxidant enzymes superoxide dismutase and catalase decreased in all tissues (P less than 0.01) while the activity of glutathione s-transferase increased in heart, but no change in other tissues. The studies thus show that lipid peroxidation is activated in liver and kidney while heart tissues show some resistance towards lipid peroxidation.

Efecto de orto-naftoquinonas lipofílicas sobre el crecimiento y la producción de peróxidos por Leptomonas seymouri y Crithidia fasciculata / Effect of lipophilic ortho-naphthoquinones on the growth and production of peroxides by Leptomonas seymouri and Crithidia fasciculata

Las §-naftoquinonas CG 8-935, CG 9-442, CG 10-248 y las mansonomas A, C, E y F inhiben el crecimiento de L. seymouri (LS) y C. fasciculata (CF). Las mansononas más activas fueron E y F (I50, 0.1 y 0.4 *M con LS y 0.3-1.2 *M con CF), con actividades citotóxicas iguales o superiores a las de las o-quinonas CG. La incubación de los protozoarios con las quinonas CG y las quinonas E y F indujo la producción de H2O2 y O2. Menor producción se obtuvo con la perezona y la priminina (p-benzoquinonas utilizadas como testigo). El efecto de las o-quinonas fue proprocional a su concentración y con las mansononas E y F la producción de O2 fue 4-5 veces mayor que la de H2O2. Diferencias menores se observaron con las quinonas CG. La producción de peróxidos resultó de un ciclo redox, iniciado por una fase anaeróbica (I) en la que se formaron los quinoles, seguida por una fase aeróbica (II) en la que se formó O2 y H2O2. Con las mansononas E y F, y las quinonas CG, la velocidad de la fase II fue superior o igual a la de la fase I pero, con las mansononas A y C, la velocidad de oxidación de los quinoles fue 8-10 veces menor que la de reducción de las quinonas. Esas diferencias concuerdan con a) la oxidación in vitro de los quinoles; b) su capacidad para producir O2 y c) su capacidad para inducir la quimiluminiscencia de la lucigenina. Los resultados descriptos demuestran la intervención de oxi-radicales en la citotoxicidad de las §-quinonas, no obstante la existencia de catalasa y otras enzimas protectoras en LS y CF, pero no se descartan otros mecanismos. La sensibilidad de ambos organismos a las quinonas estudiadas, similar o superior a la del T. cruzi, autoriza a utilizar a LS y CF como modelos para el ensayo de quimioterápicos antichagásicos

Protection of Phagocytic Macrophages from Peroxidative Damage by Selenium and Vitamin E

The Protective effect of vitamin E and selenium against peroxidative damage in white blood cells was studied. Forty-eight male rats (~100g BW) were divided into four groups and were fed with a torula yeast based diet deficient in Vit.E and Se. Vit.E (100IU/Kg diet) and Se (0.3ppm) supplementation increased the total peritoneal cell (P.C) population and cell survival rate. Selenium supplementation decreased the hydrogen peroxide generation (half of the control) significantly and Vit.E supplementation reduced the malonaldehyde production during phagocytosis in vitro. However, superoxide generation was not affected by the supplementation of Vit.E or Se. There were no significant differences in catalase activity between groups but glutathione peroxidase activity was increased about twofold by Se supplementation with no effect of Vit.E. In a separate experiment, activated alveolar macrophages were obtained from BCG infected rabbits fed a diet supplemented with Vit.E (100 IU/Kg diet) or Se (0.3 ppm). Se supplementation increased glutathione peroxidase in cells, and both Vit.E and Se increased the cell survival rate during phagocytosis as compared to the control. Both Vit.E and Se are necessary to protect host cells from peroxidative damage during phagocytosis.