title: Urinary biomarkers of oxidative stress and plasmatic inflammatory profile in phenylketonuric treated patients.
abstract: Oxidative stress has been proposed as an important pathophysiologic feature of various inborn errors of metabolism, including phenylketonuria (PKU). Considering that there are few studies relating oxidative stress and inflammation directly in PKU disease, the aim of this study was to evaluate and correlate oxidative damage to biomolecules, antioxidant defenses, pro-inflammatory cytokines, phenylalanine (Phe) and its metabolites (phenyllactic acid--PLA and phenylacetic acid--PAA) levels in urine and plasma from patients with PKU under dietary treatment. We observed a marked increase of isoprostanes, which is a lipid peroxidation biomarker, in urine from these treated patients. Next, we demonstrated that protein oxidative damage, measured by di-tyrosine formation, was significantly increased in urine from PKU treated patients and that decreased urinary antioxidant capacity was also observed. Our findings concerning to the inflammatory cytokines interleukin-6 and interleukin-1β, both significantly increased in these patients, provide evidence that the pro-inflammatory state occurs. Besides, interleukin-1β was positively correlated with isoprostanes. We observed a negative correlation between interleukin-6 and interleukin-10, an anti-inflammatory cytokine. Di-tyrosine was positively correlated with Phe, which indicates oxidative damage to proteins, as well as with PAA. These findings may suggest that the protein damage may be induced by Phe and its metabolite PAA in PKU. Our results indicate that pro-oxidant and pro-inflammatory states occur and are, in part, correlated and protein oxidation seems to be induced by Phe and PPA in PKU patients.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, CEP 90610-000 Porto Alegre, RS, Brazil; Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: marion_deon@yahoo.com.br.
authors.forename: Marion
authors.initials: M
authors.lastname: Deon
authors.affiliation: Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Angela
authors.initials: A
authors.lastname: Sitta
authors.affiliation: Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Faverzani
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, CEP 90610-000 Porto Alegre, RS, Brazil; Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Gillian B
authors.initials: GB
authors.lastname: Guerreiro
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Donida
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Desirèe P
authors.initials: DP
authors.lastname: Marchetti
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Caroline P
authors.initials: CP
authors.lastname: Mescka
authors.affiliation: Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Graziela S
authors.initials: GS
authors.lastname: Ribas
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Fisiologia, UFRGS, Rua Sarmento Leite, 500, CEP 90050-170 Porto Alegre, RS, Brazil.
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Coitinho
authors.affiliation: Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, CEP 90610-000 Porto Alegre, RS, Brazil; Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: crvargas@hcpa.edu.br.
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Vargas
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000652:urine*; D002648:Child; D003402:Creatine Kinase / Q000097:blood; D016207:Cytokines / Q000097:blood*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress; D010649:Phenylalanine; D010661:Phenylketonurias / Q000097:blood* / Q000652:urine*; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000652:urine; D017392:Thiobarbituric Acid Reactive Substances; D014443:Tyrosine; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C075750:8-epi-prostaglandin F2alpha; D014443:Tyrosine; D010649:Phenylalanine; D015237:Dinoprost; D013482:Superoxide Dismutase; D003402:Creatine Kinase
keywords: Interleukin; Lipid oxidative damage; Phenylacetic acid; Phenylalanine; Phenylketonuria; Protein oxidative damage