ABSTRACT
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.
Subject(s)
Animals , Male , Mice , Brain/drug effects , Membrane Potential, Mitochondrial/drug effects , Mercury Poisoning, Nervous System/prevention & control , Methylmercury Compounds/toxicity , Mitochondria/drug effects , Neuroprotective Agents/pharmacology , Organoselenium Compounds/pharmacology , Oxidative Stress/drug effects , Analysis of Variance , Benzene Derivatives/pharmacology , Cell Fractionation , Models, Animal , Neuroprotective Agents/classification , Organoselenium Compounds/chemistryABSTRACT
La epidermólisis bulosa distrófica (EBD) es una patología cutánea, que frecuentemente se asocia a la presencia de cánceres epidermoides cutáneos de conducta agresiva. El tratamiento quirúrgico constituye la principal modalidad de tratamiento, debido a la presencia de metástasis en forma temprana, debe consolidarse con quimioterapia o radioterapia. El uso de estas modalidades se dificulta, debido a la patología cutánea de base. Se presenta el manejo con inmunoterapia utilizando una mezcla de citocinas naturales (IRX-2), en un paciente de 27 años con cáncer epidermoide de lengua recurrente, metastásico a cuello, en quien, por sus condiciones generales, no fue posible administrar otras modalidades terapéuticas. El uso de inmunoterapia indujo una respuesta objetiva parcial y paliación sintomática sin toxicidad. El uso de este tratamiento pudiera ser considerado como manejo paliativo en pacientes con cáncer epidermoide (CE) asociado a EBD.
Subject(s)
Humans , Male , Adult , Epidermolysis Bullosa Dystrophica/diagnosis , Epidermolysis Bullosa Dystrophica/therapy , Immunotherapy , Tongue Neoplasms , Cyclophosphamide , CytokinesABSTRACT
El paludismo a P malarie es la mas antigua y la mas cosmopolita de la enfermedades producidas por protozooarios; presenta frecuentes recrudecencias despues de muchos anos de latencia debido a su marcada resistencia a la cleroquina y otros antibioticos. En Bolivia el ultimo caso denunciado data de 1979. Se descubre un caso importado del Africa que recrudecio despues de 11 anos de latencia.