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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

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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.

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Abbreviations

Arg:

Arginine

CAT:

Catalase

CSF:

Cerebrospinal fluid

DTNB:

5,5′-Dithiobis(2-nitrobenzoic acid)

GSH-Px:

Glutathione peroxidase

IEM:

Inborn error of metabolism

L-NAME:

N G-nitro-l-arginine methyl ester

MDA:

Malondialdehyde

NADPH:

Nicotinamide adenine dinucleotide phosphate

NO:

Nitric oxide

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

SPSS:

Statistical Package for the Social Sciences

TBA-RS:

Thiobarbituric acid-reactive substances

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Acknowledgments

This work was supported by grants from Universidade da Região de Joinville and Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina–FAPESC.

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

The “Principles of Laboratory Animal Care” (NIH publication 85–23, revised 1985) were followed in all the experiments and the experimental protocol was approved by the Ethics Committee for Animal Research of the University of Region Joinville, Joinville, Brazil, under the protocol number 019/2013 PRPPG/CEP.

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Authors and Affiliations

  1. 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

    Simone Sasso

  2. Departamento de Farmácia, Universidade da Região de Joinville-Univille, Rua Paulo Malschitzki, 10-Zona Industrial Norte, Joinville, SC, CEP 89201-972, Brazil

    Leticia Dalmedico & Eduardo Manoel Pereira

  3. Departamento de Ciências Naturais, Centro de Ciências Exatas e Naturais, Universidade Regional de Blumenau, Rua Antônio da Veiga, 140, Blumenau, SC, CEP 89012-900, Brazil

    Débora Delwing-Dal Magro

  4. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, Brazil

    Angela T. S. Wyse

  5. Departamento de Medicina, Universidade da Região de Joinville-Univille, Rua Paulo Malschitzki, 10-Zona Industrial Norte, Joinville, SC, CEP 89201-972, Brazil

    Daniela Delwing- de Lima

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  1. Simone Sasso
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  2. Leticia Dalmedico
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  3. Débora Delwing-Dal Magro
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  4. Eduardo Manoel Pereira
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  5. Angela T. S. Wyse
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  6. Daniela Delwing- de Lima
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Correspondence to Daniela Delwing- de Lima.

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Sasso, S., Dalmedico, L., Magro, D.DD. et al. 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. Amino Acids 47, 1931–1939 (2015). https://doi.org/10.1007/s00726-015-1973-6

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