• Gilian Guerreiro, Jéssica Faverzani, Carlos Eduardo Diaz Jacques, Desirèe P Marchetti, Angela Sitta, de Moura CoelhoDaniellaDServiço de Genética Médica, HCPA, UFRGS, Porto Alegre, RS, Brazil., Aline Kayser, Fernando Kok, Larissa Athayde, Vanusa Manfredini, Moacir Wajner, and Carmen Regla Vargas.
• Faculdade de Farmácia, UFRGS, Porto Alegre, RS, Brazil.
• J. Cell. Biochem. 2018 Dec 1; 119 (12): 10021-10032.

AbstractThe deficiency of the enzyme glutaryl-CoA dehydrogenase, known as glutaric acidemia type I (GA-I), leads to the accumulation of glutaric acid (GA) and glutarilcarnitine (C5DC) in the tissues and body fluids, unleashing important neurotoxic effects. l-carnitine (l-car) is recommended for the treatment of GA-I, aiming to induce the excretion of toxic metabolites. l-car has also demonstrated an important role as antioxidant and anti-inflammatory in some neurometabolic diseases. This study evaluated GA-I patients at diagnosis moment and treated the oxidative damage to lipids, proteins, and the inflammatory profile, as well as in vivo and in vitro DNA damage, reactive nitrogen species (RNS), and antioxidant capacity, verifying if the actual treatment with l-car (100 mg kg-1  day-1 ) is able to protect the organism against these processes. Significant increases of GA and C5DC were observed in GA-I patients. A deficiency of carnitine in patients before the supplementation was found. GA-I patients presented significantly increased levels of isoprostanes, di-tyrosine, urinary oxidized guanine species, and the RNS, as well as a reduced antioxidant capacity. The l-car supplementation induced beneficial effects reducing these biomarkers levels and increasing the antioxidant capacity. GA, in three different concentrations, significantly induced DNA damage in vitro, and the l-car was able to prevent this damage. Significant increases of pro-inflammatory cytokines IL-6, IL-8, GM-CSF, and TNF-α were shown in patients. Thus, the beneficial effects of l-car presented in the treatment of GA-I are due not only by increasing the excretion of accumulated toxic metabolites, but also by preventing oxidative damage.© 2018 Wiley Periodicals, Inc.

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