llex paraguariensis e seus componentes majoritários atenuam as alterações comportamentais, mortalidade e nos parâmetros bioquímicos associados a exposição ao malonato ou metilmalonato em Drosophila melonogaster

Abstract

Methylmalonic acidemia is a rare autosomal recessive inborn error of branched-chain amino acid metabolism that causes significant childhood morbidity and mortality and, for survivors, significant debilitating damage in adulthood. This disease is a result of a defect in mitochondrial metabolism since the decrease in activity of the enzyme methylmalonyl-CoA mutase (responsible for degrading L-Methylmalonyl-CoA to Succinyl-CoA) leads to the accumulation of organic acids in the body, including acids. malonic and methylmalonic. Although unclear the mechanism (s) by which these acids act, oxidative stress seems to contribute to the toxicity of these organic acids. Given the above, and knowing that the aqueous extract of Ilex paraguariensis (IP) has antioxidant activity, this study tests the hypothesis that IP extract, caffeic acid and caffeine may attenuate the toxicity of malonic and methylmalonic acids in a model of D. melanogaster. Our preliminary data show that IP extract attenuated behavioral damage, protected against mortality, and was able to protect against damage (oxidative and non-oxidative) associated with exposure to different organic acids. In order to better understand the mechanism (s) by which IP extract acts, we continued the study using caffeic acid and caffeine (major compounds of IP extract), either alone or in combination with co-exposure to malonic and methylmalonic acids. In view of this, the isolates reduced mortality and completely abolished behavioral changes and were able to protect against biochemical changes, thus being responsible at least in part for the protective effect of I. paraguariensis extract as reported in a previous study.