Protective effects of organoselenium compounds against methylmercury-induced oxidative stress in mouse brain mitochondrial-enriched fractions

We evaluated the potential neuroprotective effect of 1-100 µM of four organoselenium compounds: diphenyl diselenide, 3’3-ditri-fluoromethyldiphenyl diselenide, p-methoxy-diphenyl diselenide, and p-chloro-diphenyl diselenide, against methylmercury-induced mitochondrial dysfunction and oxidative stress in mitochondrial-enriched fractions from adult Swiss mouse brain. Methylmercury (10-100 µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, which occurred in parallel with increased glutathione oxidation, hydroperoxide formation (xylenol orange assay) and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with diphenyl diselenide (100 µM) completely prevented the disruption of mitochondrial activity as well as the increase in TBARS levels caused by methylmercury. The compound 3’3-ditrifluoromethyldiphenyl diselenide provided a partial but significant protection against methylmercury-induced mitochondrial dysfunction (45.4 ± 5.8 percent inhibition of the methylmercury effect). Diphenyl diselenide showed a higher thiol peroxidase activity compared to the other three compounds. Catalase blocked methylmercury-induced TBARS, pointing to hydrogen peroxide as a vector during methylmercury toxicity in this model. This result also suggests that thiol peroxidase activity of organoselenium compounds accounts for their protective actions against methylmercury-induced oxidative stress. Our results show that diphenyl diselenide and potentially other organoselenium compounds may represent important molecules in the search for an improved therapy against the deleterious effects of methylmercury as well as other mercury compounds.

Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity

This review addresses the mechanisms of methylmercury (MeHg)-induced neurotoxicity, specifically examining the role of oxidative stress in mediating neuronal damage. A number of critical findings point to a central role for astrocytes in mediating MeHg-induced neurotoxicity as evidenced by the following observations: a) MeHg preferentially accumulates in astrocytes; b) MeHg specifically inhibits glutamate uptake in astrocytes; c) neuronal dysfunction is secondary to disturbances in astrocytes. The generation of reactive oxygen species (ROS) by MeHg has been observed in various experimental paradigms. For example, MeHg enhances ROS formation both in vivo (rodent cerebellum) and in vitro (isolated rat brain synaptosomes), as well as in neuronal and mixed reaggregating cell cultures. Antioxidants, including selenocompounds, can rescue astrocytes from MeHg-induced cytotoxicity by reducing ROS formation. We emphasize that oxidative stress plays a significant role in mediating MeHg-induced neurotoxic damage with active involvement of the mitochondria in this process. Furthermore, we provide a mechanistic overview on oxidative stress induced by MeHg that is triggered by a series of molecular events such as activation of various kinases, stress proteins and other immediate early genes culminating in cell damage.

Reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta-aminolevulinate dehydratase from rat liver and cucumber leaves

The interaction of the product of H2O2 and (PhSe)2 with delta-aminolevulinate dehydratase (delta-ALA-D) from mammals and plants was investigated. (PhSe)2 inhibited rat hepatic delta-ALA-D with an IC50 of 10 æM but not the enzyme from cucumber leaves. The reaction of (PhSe)2 with H2O2 for 1 h increased the inhibitory potency of the original compound and the IC50 for animal delta-ALA-D inhibition was decreased from 10 to 2 æM. delta-ALA-D from cucumber leaves was also inhibited by the products of reaction of (PhSe)2 with H2O2 with an IC50 of 4 æM. The major product of reaction of (PhSe)2 with H2O2 was identified as seleninic acid and produced an intermediate with a lambdamax at 265 nm after reaction with t-BuSH. These results suggest that the interaction of (PhSe)2 with mammal delta-ALA-D requires the presence of cysteinyl residues in close proximity. Two cysteine residues in spatial proximity have been recently described for the mammalian enzyme. Analysis of the primary structure of plant delta-ALA-D did not reveal an analogous site. In contrast to (PhSe)2, seleninic acid, as a result of the higher electrophilic nature of its selenium atom, may react with additional cysteinyl residue(s) in mammalian delta-ALA-D and also with cysteinyl residues from cucumber leaves located at a site distinct from that found at the B and A sites in mammals. Although the interaction of organochalcogens with H2O2 may have some antioxidant properties, the formation of seleninic acid as a product of this reaction may increase the toxicity of organic chalcogens such as (PhSe)2

Zinc accumulation in phosphate granules of Ucides cordatus hepatopancreas

Amorphous phosphate granules are present in vertebrate and invertebrate organisms. The functions attributed to these structures depend on their mineral contents and organic matrix composition. In the present study we have determined zinc concentrations in the hepatopancreas of the crab Ucides cordatus from regions contaminated with zinc, and the elemental composition of hepatopancreal phosphate granules. Organisms were collected from the contaminated areas of Sepetiba Bay (SB) and Guanabara Bay (GB), and from a non-contaminated area, Ribeira Bay (RB). The first two sites are located near the metropolitan region of Rio de Janeiro city, Brazil. Atomic absorption spectroscopy (AAS) showed a significant difference (P<0.05) for zinc concentration in the hepatopancreas from organisms collected at the contaminated sites GB (210 + or - 20 µg/g dry weight) and SB (181 + or - 16 µg/g dry weight) compared to the non-contaminated site RB (76 + or - 14 µg/g dry weight). Phosphate granules isolated from hepatopancreatic tissue were studied by electron diffraction (ED), energy dispersive X-ray analysis (EDX) and electron spectroscopic imaging (ESI). ED of granules presented no diffraction spots, indicating that these structures are in an amorphous state, while EDX of granules isolated from a contaminated area contained P, Ca and Zn. Mg, Cl and Fe were also found in some of the spectra. ESI showed that O, P and Ca were colocalized in the mineralized layers of most granules observed. The correlation between the results obtained by AAS and those obtained by microanalytical techniques suggests that the hepatopancreatic granules of U. cordatus may be related to the phenomenon of heavy metal retention

Evaluación de la morbimortalidad en el servicio de emergencia del Hospital Universitario "Angel Larralde" 1991 / Evaluation of the morbimortality in the emergency service of the Hospital University \"Angel Larralde\"

Los autores presentan un estudio retrospectivo sobre quinientas noventa y dos (592) historias clínicas correspondientes a pacientes admitidos en el Servicio de Emergencia del Hospital Universitario "Angel Larralde", situado en Valencia (Estado Carabobo-Venezuela), durante un período de cuatro meses (septiembre a diciembre de 1991). Conclusiones: Más de la mitad de los pacientes hospitalizados en el Servicio eran mayores de 40 años. El 51 por ciento correspondió al sexo masculino y el 48,3 por ciento al femenino. El promedio general de estancia fue de 2,5 días. La distribución de los pacientes según especialidad revistió las siguientes características: Medicina Interna: 61,7 por ciento ; Cirugía: 23 por ciento ; y Traumatología: 15,3 por ciento . Los motivos de consulta más frecuentes fueron en orden decreciente: disnea, dolor abdominal, traumatismos, fiebre, dolor torácico, vómitos, cefalea, dolor en miembros, pérdida del conocimiento y diarrea. Las patologías más frecuentes en Medicina Interna fueron: Accidentes cerebro vasculares, hipertensión arterial, infección respiratoria, diabetes mellitus y cardiopatía isquémica. En cuanto a las quirúrgicas: Obstrucción intestinal, colecistopatía, hemoneumotórax, enfermedad inflamatoria pélvica y pancreatitis; y las traumatológicas: Traumatismos cráneo encefálicos, politraumatismos, fracturas, celulitis y artritis séptica. La mortalidad fue del 12 por ciento y las causas más frecuentes de muerte fueron el shock hipovolémico y la insuficiencia respiratoria

Enfermedad de Mondor. / Mondor's disease

Se presenta un caso de enfermedad de Mondor de localizacion abdominal (flanco izquierdo), atribuible a la realizacion de repetidos movimientos musculares de hiperextension. El proceso asentaba en territorio de la vena toracoepigastrica en su sector abdominal, por debajo del reborde costal. Los autores analizan la bibliografia referente al tema, pasando revista a los sintomas, caracteristicas semiologicas e histopatologicas, posibles etiologias y diagnosticos diferenciales

Loxoscelismo cutaneo-necrotico simple (a proposito de cinco observaciones). / Simple necrotic-cutaneous loxoscelism (apropos of 5 cases)

Se presentan cinco casos de loxoscelismo cutaneo-necrotico simple, efectuandose consideraciones sobre diferentes aspectos historicos, etiopatogenicos, clinicos y terapeuticos de la enfermedad