Longterm melatonin administration alleviates paraquat mediated oxidative stress in Drosophila melanogaster / La administración de melatonina a largo plazo mitiga el estrés oxidativo mediado por paraquat en Drosophila melanogaster

We investigated the effect of melatonin (MEL) in the activities of cytosolic superoxide dismutase (SOD) and catalase as well as in the levels of H2O2 and mitochondrial malondialdehyde (MDA) in paraquat-intoxicated Drosophila melanogaster. Paraquat (40 mM) was administrated for 36 h. Three groups of flies intoxicated with paraquat were used: PQ (exposed during 36h to paraquat), PQ-MEL (exposed during 36h to paraquat and then treated with MEL [0.43 mM] for 12 days) and PQ-Control (maintained in standard corn meal for 12 days). Two additional groups without pre-intoxication with PQ were added: Control (maintained in standard corn meal) and MEL (treated with MEL for 12 days). Immediately after PQ intoxication the concentration of MDA (17.240 ± 0.554 nmoles MDA/mg protein) and H2O2 (3.313 ± 0.086 nmol hydrogen peroxide/mg protein) and the activities of SOD and catalase (419.667 ± 0.731 and 0.216 ± 0.009 Units/mg of protein, respectively) in the PQ group were significantly increased with respect to Control. After 12 days of intoxication with PQ, the PQ-Control flies showed increases in H2O2 (4.336 ± 0.108) and MDA levels (8.620 ± 0.156), and in the activities of SOD and catalase (692.570 ± 0.433 and 0.327 ± 0.003, respectively) as compared to PQ-MEL (p<0.001). Treatment with MEL extended the life span of the groups PQ-MEL and MEL when compared to their corresponding controls. Motor activity decreased significantly in PQ-Control and PQ-MEL flies, suggesting that the damage caused by PQ affected the nervous system of flies. Our findings showed that oxidative damage caused by paraquat was observed even after 12 days and that melatonin mitigates this damage.

Investigamos el efecto de la melatonina (MEL) en la actividad de la superóxido dismutasa citosólica (SOD) y la catalasa, así como en las concentraciones del H2O2 y del malondialdehido mitocondrial (MDA) en la toxicidad inducida por paraquat (PQ) en Drosophila melanogaster. El paraquat (40 mM) fue administrado durante 36h. Tres grupos de moscas se utilizaron después de la intoxicación con paraquat: PQ (expuestas a paraquat durante 36 h), PQ-MEL (expuestas durante 36 horas a PQ y luego tratadas con MEL [0,43 mM] por 12 días) y PQ-Control (mantenidas en medio estándar por 12 días). Se incluyeron dos grupos adicionales sin pre-intoxicación con PQ: Control (mantenido en medio estándar) y MEL (tratado con MEL por 12 días). Inmediatamente después de la intoxicación con PQ, las concentraciones de MDA (17,240 ± 0,554 nmol de MDA/mg de proteína), H2O2 (3,313 ± 0,086 nmol de H2O2/mg de proteína) y las actividades de la SOD y catalasa (419,667 ± 0,731 y 0,216 ± 0,009 unidades/mg de proteína, respectivamente) se incrementaron significativamente con respecto al Control. Doce días después de la intoxicación con PQ, las moscas PQ-Control mostraron un aumento en la concentración de H2O2 (4,336 ± 0,108), de los niveles de MDA (8,620 ± 0,156) y en las actividades de la SOD y la catalasa (692,570 ± 0,433 y 0,327 ± 0,003, respectivamente) en comparación con el grupo PQ-MEL (p<0,001). El tratamiento con MEL extendió el tiempo de vida de los grupos PQ-MEL y MEL en comparación con sus correspondientes controles. La actividad motora disminuyó significativamente en las moscas de los grupos PQ-Control y PQ-MEL, lo que sugiere que el PQ afectó el sistema nervioso de las moscas. Nuestros hallazgos demostraron que el daño oxidativo causado por paraquat en las moscas fue observado aún después de 12 días de intoxicadas y que la melatonina logró mitigar este daño.

Protective effect of 4,4'-diaminodiphenylsulfone against paraquat-induced mouse lung injury

Although 4,4'-diaminodiphenylsulfone (DDS, dapsone) has been used to treat several dermatologic conditions, including Hansen disease, for the past several decades, its mode of action has remained a topic of debate. We recently reported that DDS treatment significantly extends the lifespan of the nematode C. elegans by decreasing the generation of reactive oxygen species. Additionally, in in vitro experiments using non-phagocytic human fibroblasts, we found that DDS effectively counteracted the toxicity of paraquat (PQ). In the present study, we extended our work to test the protective effect of DDS against PQ in vivo using a mouse lung injury model. Oral administration of DDS to mice significantly attenuated the lung tissue damage caused by subsequent administration of PQ. Moreover, DDS reduced the local expression of mRNA transcripts encoding inflammation-related molecules, including endothelin-1 (ET-1), macrophage inflammatory protein-1alpha (MIP-1alpha), and transforming growth factor-beta (TGF-beta). In addition, DDS decreased the PQ-induced expression of NADPH oxidase mRNA and activation of protein kinase Cmicro (PKCmicro). DDS treatment also decreased the PQ-induced generation of superoxide anions in mouse lung fibroblasts. Taken together, these data suggest the novel efficacy of DDS as an effective protective agent against oxidative stress-induced tissue damages.