RESUMEN
Muscle dysfunction in acute organophosphorus (OP) poisoning is a cause of death in human. The present study was conducted to identify the mechanism of action of OP in terms of muscle mitochondrial dysfunction. Electromyography (EMG) was conducted on rats exposed to the acute oral dose of malathion (400 mg/kg) that could inhibit acetylcholinesterase activity up to 70%. The function of mitochondrial respiratory chain and the rate of production of reactive oxygen species (ROS) from intact mitochondria were measured. The bioenergetic pathways were studied by measurement of adenosine triphosphate (ATP), lactate, and glycogen. To identify mitochondrial-dependent apoptotic pathways, the messenger RNA (mRNA) expression of bax and bcl-2, protein expression of caspase-9, mitochondrial cytochrome c release, and DNA damage were measured. The EMG confirmed muscle weakness. The reduction in activity of mitochondrial complexes and muscular glycogen with an elevation of lactate was in association with impairment of cellular respiration. The reduction in mitochondrial proapoptotic stimuli is indicative of autophagic process inducing cytoprotective effects in the early stage of stress. Downregulation of apoptotic signaling may be due to reduction in ATP and ROS, and genotoxic potential of malathion. The maintenance of mitochondrial integrity by means of artificial electron donors and increasing exogenous ATP might prevent toxicity of OPs.
Asunto(s)
Insecticidas/toxicidad , Malatión/toxicidad , Mitocondrias Musculares/efectos de los fármacos , Enfermedades Mitocondriales/inducido químicamente , Músculo Esquelético/efectos de los fármacos , 8-Hidroxi-2'-Desoxicoguanosina , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/fisiología , Animales , Factor Apoptótico 1 Activador de Proteasas/metabolismo , Caspasa 9/metabolismo , Muerte Celular/efectos de los fármacos , Citocromos c/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Complejo I de Transporte de Electrón/efectos de los fármacos , Complejo I de Transporte de Electrón/metabolismo , Complejo II de Transporte de Electrones/efectos de los fármacos , Complejo II de Transporte de Electrones/metabolismo , Complejo IV de Transporte de Electrones/efectos de los fármacos , Complejo IV de Transporte de Electrones/metabolismo , Glucógeno/metabolismo , Ácido Láctico/metabolismo , Enfermedades Mitocondriales/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Ratas , Especies Reactivas de Oxígeno/metabolismo , Proteína X Asociada a bcl-2/biosíntesisRESUMEN
A quantitative approach has been proposed to evaluate the competitive inhibition of Escherichia coli and Salmonella typhi by live and heat-inactivated laboratory isolated Lactobacillus sp. on adhesion to monolayer of Caco-2 cells. Three species of Lactobacillus (L. casei, L. acidophilus, L. agilis) isolated from human neonate feces and two commercial probiotic strains (L. casei, L. acidophilus) have been compared for probiotic activity. All lactobacilli were able to attach to the Caco-2 cells, however, the degree of adhesion was bacterial strain-dependent. The adhesion indices of the two commercial probiotic strains were not significantly different from the values obtained for the other two similar fecal strains (p > 0.01). The inhibition of attachment of the pathogenic bacteria by inactivated cells of fecal L. acidophilus was examined and compared to the results of live bacteria. The inhibition pattern was similar for live and heat-inactivated L. acidophilus (p > 0.01). The number of attached pathogenic bacteria to the Caco-2 cells decreased when the number of L. acidophilus increased from 10(6) to 10(9) CFU/mL. The heat-inactivated L. acidophilus displayed similar probiotic activity compared to the live bacteria.