title: Oxidative Stress in Homocystinuria Due to Cystathionine ß-Synthase Deficiency: Findings in Patients and in Animal Models.
abstract: Homocystinuria is an inborn error of amino acid metabolism caused by deficiency of cystathionine ß-synthase (CBS) activity, biochemically characterized by homocysteine (Hcy) and methionine (Met) accumulation in biological fluids and high urinary excretion of homocystine. Clinical manifestations include thinning and lengthening of long bones, osteoporosis, dislocation of the ocular lens, thromboembolism, and mental retardation. Although the pathophysiology of this disease is poorly known, the present review summarizes the available experimental findings obtained from patients and animal models indicating that oxidative stress may contribute to the pathogenesis of homocystinuria. In this scenario, several studies have shown that enzymatic and non-enzymatic antioxidant defenses are decreased in individuals affected by this disease. Furthermore, markers of lipid, protein, and DNA oxidative damage have been reported to be increased in blood, brain, liver, and skeletal muscle in animal models studied and in homocystinuric patients, probably as a result of increased free radical generation. On the other hand, in vitro and in vivo studies have shown that Hcy induces reactive species formation in brain, so that this major accumulating metabolite may underlie the oxidative damage observed in the animal model and human condition. Taken together, it may be presumed that the disruption of redox homeostasis may contribute to the tissue damage found in homocystinuria. Therefore, it is proposed that the use of appropriate antioxidants may represent a novel adjuvant therapy for patients affected by this disease.
authors.affiliation: Departamento de Análises, Faculdade de Farmácia, UFRGS, Avenida Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil.|Serviço de Genética Médica HCPA, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Jéssica Lamberty
authors.initials: JL
authors.lastname: Faverzani
authors.affiliation: Departamento de Análises, Faculdade de Farmácia, UFRGS, Avenida Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil.|Serviço de Genética Médica HCPA, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Tatiane Grazieli
authors.initials: TG
authors.lastname: Hammerschmidt
authors.affiliation: Serviço de Genética Médica HCPA, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Angela
authors.initials: A
authors.lastname: Sitta
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000, Brazil.|Serviço de Genética Médica HCPA, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Marion
authors.initials: M
authors.lastname: Deon
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil.|Serviço de Genética Médica HCPA, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.affiliation: Departamento de Análises, Faculdade de Farmácia, UFRGS, Avenida Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil. crvargas@hcpa.edu.br.|Programa de Pós-Graduação em Ciências Biológicas Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil. crvargas@hcpa.edu.br.|Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000, Brazil. crvargas@hcpa.edu.br.|Serviço de Genética Médica HCPA, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil. crvargas@hcpa.edu.br.
authors.forename: Carmen Regla
authors.initials: CR
authors.lastname: Vargas
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000172:deficiency*; D004195:Disease Models, Animal; D006712:Homocystinuria / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D000975:Antioxidants; D003541:Cystathionine beta-Synthase
keywords: Animal models; Antioxidants; Homocysteine; Homocystinuria; Homocystinuric patients; Oxidative stress