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Biochemical regulatory processes in the control of oxidants and antioxidants production in the brain of rats with iron and copper chronic overloads

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Abstract

Iron [Fe(II)] and copper [Cu(II)] overloads in rat brain are associated with oxidative stress and damage. The purpose of this research is to study whether brain antioxidant enzymes are involved in the control of intracellular redox homeostasis in the brain of rats male Sprague–Dawley rats (80–90 g) that received drinking water supplemented with either 1.0 g/L of ferrous chloride (n = 24) or 0.5 g/L cupric sulfate (n = 24) for 42 days. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione transferase (GT) activities in brain were determined by spectrophotometric methods and NO production by the content of nitrite concentration in the organ. Chronic treatment with Fe(II) and Cu(II) led to a significant decrease of nitrite content and SOD activity in brain. Activity of NADPH oxidase increased with Cu(II) treatment. Concerning Fe(II), catalase and GT activities increased in brain after 28 and 4 days of treatment, respectively. In the case of Cu(II), catalase activity decreased whereas GT activity increased after 2 and 14 days, respectively. The regulation of redox homeostasis in brain involves changes of the activity of these enzymes to control the steady state of oxidant species related to redox signaling pathways upon Cu and Fe overload. NO may serve to detoxify cells from superoxide anion and hydrogen peroxide with the concomitant formation of peroxynitrite. However, the latest is a powerful oxidant which leads to oxidative modifications of biomolecules. These results suggest a common pathway to oxidative stress and damage in brain for Cu(II) and Fe(II).

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Abbreviations

ATP7A:

ATPase copper exporter protein

BBB:

Blood–brain barrier

CDNB:

1 Chlorine-2,4 dinitro benzene

C50 :

Metal content necessary to produce the half of the maximal effect

Ctr1:

Copper transporter receptor 1

Cu:

Copper

Cu(II):

Divalent copper ion

Fe:

Iron

Fe(II):

Divalent iron ion

GPx:

Glutathione peroxidase

GS-DNB:

Glutathione-dinitrobenzene

GSH:

Glutathione

GT:

Glutathione transferase

H2O2 :

Hydrogen peroxide

HO• :

Hydroxyl radical

NADPH:

Nicotinamide adenine dinucleotide phosphate oxidase

NO− :

Nitroxyl anion

NO+ :

Nitrosonium cation

NO:

Nitric oxide

N2O3 :

Dinitrogen trioxide

O2 :

Oxygen

ONNO− :

Peroxynitrite

O2 − :

Superoxide anion

1O2 :

Singlet oxygen

RNS:

Reactive nitrogen species

ROOH:

Organic hydroperoxides

ROO. :

Hydroperoxyl radical

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

SOD:

Superoxide dismutase

t 1/2 :

Time necessary to produce the half of the maximal effect

Tf:

Transferrin

TfR:

Transferrin receptor

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Acknowledgements

The authors thank Professor Alberto Boveris for his teachings and scientific contributions at the beginning of this research work, guiding the development of this experimental line.

Funding

This study was supported by grants from the University of Buenos Aires (UBACyT 20020170100197BA); the National Research Council of Argentina (CONICET) and the National Agency of Science and Technology of Argentina (ANPCYT) (PICT-2016–002077).

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Authors and Affiliations

  1. Facultad de Farmacia Y Bioquímica, Departamento de Ciencias Químicas, Cátedra de Química General E Inorgánica, Universidad de Buenos Aires, Junin 956, CP: 1113AAD, Buenos Aires, Argentina

    Christian Saporito-Magriñá, Fabiana Lairion, Rosario Musacco-Sebio & Marisa Gabriela Repetto

  2. Facultad de Farmacia Y Bioquímica, Departamento de Fisicomatemática, Cátedra de Física, Universidad de Buenos Aires, Buenos Aires, Argentina

    Julian Fuda & Horacio Torti

  3. Instituto de Bioquímica Y Medicina Molecular Prof. Alberto Boveris(CONICET, IBIMOL), Consejo Nacional de Investigaciones Científicas Y Técnicas, Buenos Aires, Argentina

    Marisa Gabriela Repetto

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  1. Christian Saporito-Magriñá
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  2. Fabiana Lairion
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  3. Rosario Musacco-Sebio
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  4. Julian Fuda
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  6. Marisa Gabriela Repetto
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Contributions

CS-M: methodology, validation, investigation, visualization, FL: validation, formal analysis, methodology, investigation, writing-original-draft, RM-S: methodology, investigation, JF: investigation, HT: investigation, resources, MGR: conceptualization, formal analysis, writing-original-draft, writing, review and editing, project administration, funding acquisition.

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Correspondence to Marisa Gabriela Repetto.

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Saporito-Magriñá, C., Lairion, F., Musacco-Sebio, R. et al. Biochemical regulatory processes in the control of oxidants and antioxidants production in the brain of rats with iron and copper chronic overloads. J Biol Inorg Chem 27, 665–677 (2022). https://doi.org/10.1007/s00775-022-01960-5

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