title: In vitro stimulation of oxidative stress in cerebral cortex of rats by the guanidino compounds accumulating in hyperargininemia.
abstract: Hyperargininemia is a metabolic disorder biochemically characterized by tissue accumulation of arginine and other guanidino compounds. Convulsions, lethargy and psychomotor delay or cognitive deterioration are predominant clinical features of this disease. Although neurologic symptoms predominate in this disorder, their pathophysiology is still unknown. In the present study we investigated the in vitro effects of arginine, N-acetylarginine, argininic acid and homoarginine on some oxidative stress parameters in rat brain in the hope to identify a possible mechanism for the brain damage in hyperargininemia. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were measured in the cerebral cortex of rats in the presence of various concentrations of these compounds. The results showed that all guanidino compounds tested significantly increased chemiluminescence and decreased TRAP at concentrations similar to those observed in the tissue of hyperargininemic patients. Furthermore, these compounds inhibited CAT and GSH-Px activities to varying extents, with GSH-Px activity being more susceptible to their action. In turn, argininic acid inhibited all enzyme activities, and its main action was also directed towards GSH-Px. The results suggest that oxidative stress caused by guanidino compounds may be involved in the brain dysfunction amongst other potential pathophysiological mechanisms observed in hyperargininemia.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre RS, Brazil. wyse@ufrgs.br
authors.forename: A T
authors.initials: AT
authors.lastname: Wyse
authors.forename: C S
authors.initials: CS
authors.lastname: Bavaresco
authors.forename: M E
authors.initials: ME
authors.lastname: Hagen
authors.forename: D
authors.initials: D
authors.lastname: Delwing
authors.forename: C M
authors.initials: CM
authors.lastname: Wannmacher
authors.forename: C
authors.initials: C
authors.lastname: Severo Dutra-Filho
authors.forename: M
authors.initials: M
authors.lastname: Wajner
mesh_terms: D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006709:Homoarginine / Q000494:pharmacology; D020162:Hyperargininemia / Q000139:chemically induced / Q000378:metabolism*; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D006709:Homoarginine; C000225:argininic acid; D001120:Arginine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C000015:N-acetyl-L-arginine