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

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

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. This study evaluated the lipid peroxidation by the measurement of 8-isoprostanes, nitrosativ...

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Bibliographic Details
Published in:Archives of biochemistry and biophysics Vol. 679; p. 108206
Main Authors: de Moraes, Maira Silmara, Guerreiro, Gilian, Sitta, Angela, de Moura Coelho, Daniella, Manfredini, Vanusa, Wajner, Moacir, Vargas, Carmen Regla
Format: Journal Article
Language:English
Published: United States Elsevier Inc 15-01-2020
Subjects:
Carnitine - pharmacology
DNA Damage
Fatty Acids - metabolism
Female
Humans
l-carnitine
LCHADD
MADD
Male
MCADD
Mitochondrial Diseases - genetics
Mitochondrial Diseases - metabolism
Oxidation-Reduction - drug effects
Oxidative stress
Oxidative Stress - drug effects
Oxidative stress
IMD
NO
DI
DNA damage
FAOD
LCHADD
RNS
MCADD
MADD
L-car
ROS
OGS
l-carnitine
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Summary: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. 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. 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. 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. This work demonstrated oxidative stress in FAOD patients and the genotoxic potential of MCADD metabolites and the protective effect of l-carnitine. •Urine from LCHADD, MCADD and MADD patients presented lipid damage.•LCHADD patients presented nitrosative stress.•LCHADD and MADD patients presented oxidative DNA and RNA damage.•MCADD metabolites, separated and in combination, induced in vitro DNA damage.•Co-incubation with l-carnitine reduced the DNA damage induced by MCADD metabolites.
ISSN:0003-9861
1096-0384
DOI:10.1016/j.abb.2019.108206