title: Protective effect of L-carnitine on Phenylalanine-induced DNA damage.
abstract: The pathogenesis and the progression of phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism, have been associated with oxidative damage. Moreover, it has been increasingly postulated the antioxidant properties of L-Carnitine (LC). The aim of this study was to verify the effect of LC on Phe-induced DNA damage. The in vitro effect of different concentrations of LC (15, 30, 120 and 150 μM) on DNA damage-induced by high phenylalanine levels (1000 and 2500 μM) was examined in white blood cells from normal individuals using the comet assay. Urinary 8-hydroxydeoguanosine (8-OHdG) levels, a biomarker of oxidative DNA damage, and plasmatic sulfhydryl content were measured in eight patients with classical PKU, under therapy with protein restriction and supplemented with a special formula containing LC, and in controls individuals. Both in vitro tested Phe concentrations (1000 and 2500 μM) have resulted in DNA damage index significantly higher than control group. The in vitro co-treatment with Phe and LC reduced significantly DNA damage index when compared to Phe group. The urinary excretion of 8-OHdG and plasmatic sulfhydryl content presented similar levels in both groups analyzed (controls and treated PKU patients). In treated PKU patients, urinary 8-OHdG levels were positively correlated with blood Phe levels and negatively correlated with blood LC concentration and plasmatic sulfhydryl content. The present work yields experimental evidence that LC can reduce the in vitro DNA injury induced by high concentrations of phenylalanine, as well as, allow to hypothesize that LC protect against DNA damage in patients with PKU.
authors.affiliation: Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003, Porto Alegre, RS, Brazil, marion_deon@yahoo.com.br.
authors.forename: Marion
authors.initials: M
authors.lastname: Deon
authors.forename: Sharon S
authors.initials: SS
authors.lastname: Landgraf
authors.forename: Jessica F
authors.initials: JF
authors.lastname: Lamberty
authors.forename: Dinara J
authors.initials: DJ
authors.lastname: Moura
authors.forename: Jenifer
authors.initials: J
authors.lastname: Saffi
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Vargas
mesh_terms: D000293:Adolescent; D002331:Carnitine / Q000494:pharmacology* / Q000627:therapeutic use; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D008297:Male; D010649:Phenylalanine / Q000633:toxicity*; D010661:Phenylketonurias / Q000097:blood / Q000188:drug therapy / Q000652:urine; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D020011:Protective Agents; D010649:Phenylalanine; D002331:Carnitine