Diphenyl diselenide modulates gene expression of antioxidant enzymes in the cerebral cortex, hippocampus and striatum of female hypothyroid rats.

Abstract

INTRODUCTION:

Cellular antioxidant signaling can be altered either by thyroid disturbances or by selenium status.

AIMS:

To investigate whether or not dietary diphenyl diselenide can modify the expression of genes of antioxidant enzymes and endpoint markers of oxidative stress under hypothyroid conditions.

METHODS:

Female rats were rendered hypothyroid by continuous exposure to methimazole (MTZ; 20 mg/100 ml in the drinking water) for 3 months. Concomitantly, MTZ-treated rats were either fed or not with a diet containing diphenyl diselenide (5 ppm). mRNA levels of antioxidant enzymes and antioxidant/oxidant status were determined in the cerebral cortex, hippocampus and striatum.

RESULTS:

Hypothyroidism caused a marked upregulation in mRNA expression of catalase, superoxide dismutase (SOD-1, SOD-3), glutathione peroxidase (GPx-1, GPx-4) and thioredoxin reductase (TrxR-1) in brain structures. SOD-2 was increased in the cortex and striatum, while TrxR-2 increased in the cerebral cortex. The increase in mRNA expression of antioxidant enzymes was positively correlated with the Nrf-2 transcription in the cortex and hippocampus. Hypothyroidism caused oxidative stress, namely an increase in lipid peroxidation and reactive oxygen species levels in the hippocampus and striatum, and a decrease in nonprotein thiols in the cerebral cortex. Diphenyl diselenide was effective in reducing brain oxidative stress and normalizing most of the changes observed in gene expression of antioxidant enzymes.

CONCLUSION:

The present work corroborates and extends that hypothyroidism disrupts antioxidant enzyme gene expression and causes oxidative stress in the brain. Furthermore, diphenyl diselenide may be considered a promising molecule to counteract these effects in a hypothyroidism state.

• Authors: Glaecir Roseni Mundstock Dias, Ronaldo Medeiros Golombieski, Rafael de Lima Portella, Guilherme Pires do Amaral, Félix Antunes Soares, João Batista Teixeira da Rocha, Cristina Wayne Nogueira, Nilda Vargas Barbosa
• Journal: Neuroendocrinology (Neuroendocrinology) Vol. 100 Issue 1 Pg. 45-59 ( 2014) ISSN: 1423-0194 [Electronic] Switzerland
• PMID: 25012258 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Antioxidants
• Benzene Derivatives
• NF-E2-Related Factor 2
• Nfe2l2 protein, rat
• Organoselenium Compounds
• RNA, Messenger
• Reactive Oxygen Species
• Sulfhydryl Compounds
• diphenyldiselenide
• Methimazole

Topics

• Animals
• Antioxidants (metabolism)
• Benzene Derivatives (administration & dosage)
• Body Weight
• Cerebral Cortex (enzymology)
• Corpus Callosum (enzymology)
• Disease Models, Animal
• Female
• Hippocampus (enzymology)
• Hypothyroidism (diet therapy, enzymology)
• Lipid Peroxidation (physiology)
• Methimazole
• NF-E2-Related Factor 2 (metabolism)
• Organoselenium Compounds (administration & dosage)
• Oxidative Stress (physiology)
• RNA, Messenger (metabolism)
• Random Allocation
• Rats, Wistar
• Reactive Oxygen Species (metabolism)
• Sulfhydryl Compounds (metabolism)