title: Diphenyl diselenide modulates gene expression of antioxidant enzymes in the cerebral cortex, hippocampus and striatum of female hypothyroid rats.
abstract: BACKGROUND
  Cellular antioxidant signaling can be altered either by thyroid disturbances or by selenium status.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Programa de Pós-Graduação em Bioquímica Toxicológica, Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Glaecir
authors.initials: G
authors.lastname: Roseni Mundstock Dias
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Medeiros Golombieski
authors.forename: Rafael
authors.initials: R
authors.lastname: de Lima Portella
authors.forename: Guilherme
authors.initials: G
authors.lastname: Pires do Amaral
authors.forename: Félix
authors.initials: F
authors.lastname: Antunes Soares
authors.forename: João Batista
authors.initials: JB
authors.lastname: Teixeira da Rocha
authors.forename: Cristina
authors.initials: C
authors.lastname: Wayne Nogueira
authors.forename: Nilda
authors.initials: N
authors.lastname: Vargas Barbosa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001555:Benzene Derivatives / Q000008:administration & dosage*; D001835:Body Weight; D002540:Cerebral Cortex / Q000201:enzymology*; D003337:Corpus Callosum / Q000201:enzymology*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000201:enzymology*; D007037:Hypothyroidism / Q000178:diet therapy* / Q000201:enzymology; D015227:Lipid Peroxidation / Q000502:physiology; D008713:Methimazole; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016566:Organoselenium Compounds / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001555:Benzene Derivatives; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D016566:Organoselenium Compounds; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; C061132:diphenyldiselenide; D008713:Methimazole