title: Differential in vitro effects of homoarginine on oxidative stress in plasma, erythrocytes, kidney and liver of rats in the absence and in the presence α-tocopherol, ascorbic acid or L-NAME.
abstract: In the present study, we evaluated the in vitro effects of homoarginine (hArg) at 1, 10 and 20 µM on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in plasma, erythrocytes, kidney and liver of rats (60 days old). We also investigated the influence of the antioxidants (each at 1 mM) α-tocopherol and ascorbic acid, as well as of the nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester (L-NAME) at 1 mM, on the effects elicited by hArg on the parameters tested. In plasma, hArg at concentrations of 10 and 20 μM decreased moderately the total sulfhydryl content. At 20 µM, hArg enhanced moderately TBA-RS in the plasma. In plasma, the effects of hArg (20 µM) on TBA-RS and total thiol content were abolished by α-tocopherol, ascorbic acid and L-NAME. At all concentrations tested, hArg did not exert any effect on CAT, SOD or GSH-Px activity in the erythrocytes. In the kidney, hArg exerted effects only at 20 µM and in a different manner: TBA-RS levels increased and total thiol content and CAT activity decreased, while SOD and GSH-Px activity increased. In the renal medulla, α-tocopherol and ascorbic acid but not L-NAME abolished the effects of hArg (20 µM) on TBA-RS, while all agents inhibited the hArg-induced increase in SOD activity. In the renal cortex, α-tocopherol, ascorbic acid and L-NAME abolished the effects of hArg (20 µM) on the total sulfhydryl content and GSH-Px activity, but L-NAME did not reverse the inhibitory effects of hArg on CAT activity. In the liver, no effects of hArg were observed of all biomarkers measured. At the pathologically high concentration of 20 µM, as it may occur in plasma in hyperargininemia, hArg may enhance lipid peroxidation and thiol oxidation and inhibit CAT activity, but may increase SOD and GSH-Px activity predominantly in the kidney.
authors.affiliation: Mestrado em Saúde e Meio Ambiente, Universidade da Região de Joinville-Univille, Rua Paulo Malschitzki, 10-Zona Industrial Norte, Joinville, SC, CEP 89201-972, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Sasso
authors.forename: Leticia
authors.initials: L
authors.lastname: Dalmedico
authors.forename: Débora Delwing-Dal
authors.initials: DD
authors.lastname: Magro
authors.forename: Eduardo Manoel
authors.initials: EM
authors.lastname: Pereira
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
authors.forename: Daniela Delwing-
authors.initials: DD
authors.lastname: de Lima
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D004912:Erythrocytes / Q000378:metabolism*; D006709:Homoarginine / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D006709:Homoarginine; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D019331:NG-Nitroarginine Methyl Ester