La suplementación con ácido ascórbico atenúa el trastorno metabólico inducido por un derivado de juglona / Ascorbic supplementation attenuates juglone induced metabolic derangement

Los derivados de juglona, como 2-(4-hidroxifenil) amino-1,4-naftoquinona (Q7), son conocidos agentes antitumorales. Ellos generan especies reactivas de oxígeno (ROS), que podrían producir un desbalance de ROS y un metabolismo anormal de lípidos. El objetivo del estudio fue evaluar el efecto del ascorbato sobre el metabolismo de lípidos y carbohidratos en condición de estrés oxidativo inducido por Q7. A ratas Wistar macho, se les administró oralmente Q7 (10 mg/Kg) y/o ascorbato (500 mg/Kg) durante 20 días. Las ratas tratadas con Q7 mostraron un aumento de los triglicéridos en suero, del colesterol VLDL y de los niveles de peróxidación lipídica. Cuando el tratamiento con Q7 fue seguido de la administración de ascorbato (500 mg/Kg), observamos una disminución de los triglicéridos en suero, del colesterol VLDL y de la peroxidación lipídica. La administración oral de ascorbato redujo el aumento de lípidos inducido por Q7 y la glicemia postprandial. Esto podría estar asociado con la actividad redox del ascorbato, que reduce el estrés oxidativo inducido por Q7. Concluimos que el ascorbato modula el aumento del metabolismo de lípidos y carbohidratos inducido por Q7.

Juglone derivatives like 2-(4-hydroxyphenyl) amino-1,4-naphthoquinone (Q7) are used as antitumor agents, and act through reactive oxygen species (ROS) generation. Such may lead to abnormal lipid metabolism and ROS dysregulation. The objective of this study was to evaluate the effect of ascorbate on the metabolism of lipids and carbohydrates following Q7-induced oxidative stress. Male Wistar rats were administered Q7 (10 mg/Kg) and/or ascorbate (500 mg/Kg) orally for 20 days. Rats treated with Q7 showed an increase in serum triglycerides, VLDL cholesterol and lipid peroxidation levels. When Q7 treatment was followed up by ascorbate (500 mg/Kg) administration, we observed a reduction in serum triglycerides, VLDL cholesterol and lipid peroxidation. The oral administration of ascorbate reduced the Q7-induced increases in lipids, and postprandial glycemia. This could be associated with the redox activity of ascorbate that reduced the oxidative stress induced by Q7. We thus conclude that ascorbate modulates the Q7-induced increase of lipid and carbohydrate metabolism.

Ascorbate Attenuates Oxidative Stress and Increased Blood Pressure Induced by 2-(4-Hydroxyphenyl) Amino-1,4-naphthoquinone in Rats.

Quinone derivatives like 2-(4-hydroxyphenyl) amino-1,4-naphthoquinone (Q7) are used as antitumor agents usually associated with adverse effects on the cardiovascular system. The objective of this study was to evaluate the cardioprotective effect of ascorbate on Q7-induced cardiovascular response in Wistar rats. In this study, blood pressure, vascular reactivity, and intracellular calcium fluxes were evaluated in cardiomyocytes and the rat aorta. We also measured oxidative stress through lipid peroxidation (TBARS), superoxide dismutase- (SOD-) like activity, and H2O2 generation. Oral treatment of rats with ascorbate (500 mg/kg) for 20 days significantly (p < 0.05) reduced the Q7-induced increase (10 mg/kg) in blood pressure and heart rate. The preincubation with ascorbate (2 mM) significantly (p < 0.05) attenuated the irregular beating of the atrium induced by Q7 (10-5 M). In addition, ascorbate induced endothelial vasodilation in the presence of Q7 in the intact aortic rings of a rat and reduced the cytosolic calcium levels in vascular smooth muscle cells. Ascorbate also reduced the Q7-induced oxidative stress in vivo. Ascorbate also attenuated Q7-induced SOD-like activity and increased TBARS levels. These results suggest a cardioprotective effect in vivo of ascorbate in animals treated orally with a naphthoquinone derivative by a mechanism involving oxidative stress.