Oxidative damage in mitochondrial fatty acids oxidation disorders patients and the in vitro effect of l-carnitine on DNA damage induced by the accumulated metabolites.

BACKGROUND: The mitochondrial fatty acids oxidation disorders (FAOD) are inherited metabolic disorders (IMD) characterized by the accumulation of fatty acids of different sizes of chain according to the affected enzyme. METHODS: This study evaluated the lipid peroxidation by the measurement of 8-isoprostanes, nitrosative stress parameters by the measurement of nitrite and nitrate content and DNA and RNA oxidative damage by the measurement of oxidized guanine species in urine samples from long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and multiple acyl-CoA dehydrogenase deficiency (MADD) patients. Also, we analyzed the in vitro DNA damage by comet assay induced by adipic acid, suberic acid, hexanoylglycine and suberylglycine, separated and in combination, as well as the effect of l-carnitine in human leukocytes. RESULTS: An increase on 8-isoprostanes levels in all groups of patients was observed. The nitrite and nitrate levels were increased in LCHADD patients. DNA and RNA damage evaluation revealed increase on oxidized guanine species levels in LCHADD and MADD patients. The in vitro evaluation revealed an increase on the DNA damage induced by all metabolites, besides a potencialyzed effect. l-carnitine decreased the DNA damage induced by the metabolites. CONCLUSION: These results demonstrate that toxic metabolites accumulated could be related to the increased oxidative and nitrosative stress of FAOD patients and that the metabolites, separated and in combination, cause DNA damage, which was reduced by l-carnitine, demonstrating antioxidant protection. GENERAL SIGNIFICANCE: This work demonstrated oxidative stress in FAOD patients and the genotoxic potential of MCADD metabolites and the protective effect of l-carnitine.

Effects of Methanol Fraction from Leaves of Schinus terebinthifolius Raddi on Nociception and Spinal-Cord Oxidative Biomarkers in Rats with Neuropathic Pain.

We determined the antioxidant potential of fractions obtained from leaves of Schinus terebinthifolius, a medicinal plant known in Brazil as aroeira, to select the fraction with the best yield and antioxidant performance. These qualities were found in the methanol fraction (MeF), which was administered intraperitoneally (20 mg/kg/day) for 3 and 10 days to rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. The MeF increased the mechanical and thermal thresholds that had been lowered by CCI. In parallel, the lumbosacral spinal cord showed an increase in superoxide dismutase but a decrease in glutathione peroxidase and glutathione-S-transferase activities in saline- and MeF-treated CCI rats. Catalase activity decreased only in saline-treated CCI rats for 10 days. Total thiols decreased in saline- and MeF-treated CCI rats. Ascorbic acid increased in these rats at day 3 but only in saline-treated CCI rats at day 10. No change was found in hydrogen peroxide and lipid hydroperoxide. Open-field and elevated plus-maze tests and blood parameters of liver function did not change. Thus, the MeF from leaves of S. terebinthifolius has an antinociceptive action with no toxic effects, and it affects oxidant biomarkers in the spinal cord of rats with CCI.