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Increased cerebral oxidative damage and decreased antioxidant defenses in ovariectomized and sham-operated rats supplemented with vitamin A

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Abstract

Previous studies have linked oxidative stress with aging and aging-related processes, including menopause. Abnormalities in the redox state similar to those observed in menopausal women can be modeled experimentally with rat ovariectomy. The aim of the present study was to investigate the effects of vitamin A (retinol palmitate) supplementation (500 or 1,500 IU kg−1 day−1 for 30 days) on behavioral parameters and brain redox profile in ovariectomized (OVX) and sham-operated rats. Ovariectomy caused pronounced uterine atrophy and decreased locomotor/exploratory activity. Moreover, we found increased hypothalamic and frontal cortex superoxide dismutase/catalase (SOD/CAT) ratio and decreased hippocampal thiol content, accompanied by increased frontal cortex lipid oxidative damage (TBARS) in OVX rats. Vitamin A at 1,500 IUkg−1 day−1 decreased exploratory behavior and decreased total hippocampal thiol content in sham-operated rats, increased hippocampal SOD/CAT ratio and decreased total antioxidant potential in the hippocampus of both sham and OVX groups, and increased cortical TBARS levels in OVX rats. Thus, vitamin A may induce a pro-oxidant state in discrete brain regions of sham-operated and OVX rats. These results suggest some caution regarding the use of high doses of vitamin A supplementation during menopause.

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Abbreviations

AUC:

Area under curve

CAT:

Catalase

CNS:

Central nervous system

EPM:

Elevated plus maze

H2O2 :

Hydrogen peroxide

HRT:

Hormone replacement therapy

MDA:

Malondialdehyde

O2 :

Superoxide anion

OFT:

Open-field test

OVX:

Ovariectomized

ROS:

Reactive oxygen species

SH:

Sulfhydryl

SOD:

Superoxide dismutase

TBARS:

Thiobarbituric acid reactive species

TRAP:

Total radical antioxidant potential

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Acknowledgments

This work was supported by grants from a Brazilian public agency, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq–Brazil). G.A. Behr, C.E. Schnorr, A. Simões-Pires and L.L. da Motta are recipients of CNPq scholarships. G.A. Behr was recipient of Capes scholarship—Proc. No. BEX 5383/10-2. The authors also thank the Universidade Federal do Rio Grande do Sul (UFRGS), a federal public university from Brazil.

Conflict of Interest Statement

The authors declare no conflicts of interest related to the present report.

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Authors and Affiliations

  1. Center of Oxidative Stress Research, Professor Tuiskon Dick Department of Biochemistry, Institute of Health Basic Sciences, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos Street, 2600-Anexo, 90035-003, Porto Alegre, RS, Brazil

    Guilherme Antonio Behr, Carlos Eduardo Schnorr, André Simões-Pires, Leonardo Lisbôa da Motta & José Cláudio Fonseca Moreira

  2. Capes Foundation, Ministry of Education of Brazil, Caixa Postal 250, 70040-020, Brasília, DF, Brazil

    Guilherme Antonio Behr

  3. Women’s Health Concerns Clinic and Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, 301 James Street South, Suite F614, Hamilton, ON, L8P 3B6, Canada

    Guilherme Antonio Behr & Benicio N. Frey

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  1. Guilherme Antonio Behr
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  2. Carlos Eduardo Schnorr
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Correspondence to Guilherme Antonio Behr.

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Behr, G.A., Schnorr, C.E., Simões-Pires, A. et al. Increased cerebral oxidative damage and decreased antioxidant defenses in ovariectomized and sham-operated rats supplemented with vitamin A. Cell Biol Toxicol 28, 317–330 (2012). https://doi.org/10.1007/s10565-012-9226-x

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