title: Hypothyroidism minimizes the effects of acute hepatic failure caused by endoplasmic reticulum stress and redox environment alterations in rats.
abstract: The aim of this study was to investigate if a protective effect from hypothyroidism in acute liver failure resulted from reduced endoplasmic reticulum stress and changes to the redox environment. Twenty male Sprague-Dawley rats were divided in four groups: (1) euthyroid (sham surgery), (2) hypothyroid, (3) euthyroid (sham surgery)+thioacetamide and (4) hypothyroid+thioacetamide. Hypothyroidism was confirmed two weeks after thyroidectomy, and thioacetamide (TAA) (400mg/kg, ip) was administrated to the appropriate groups for three days with supportive therapy. Grades of encephalopathy in all animals were determined using behavioral tests. Animals were decapitated and their blood was obtained to assess liver function. The liver was dissected: the left lobe was used for histology and the right lobe was frozen for biochemical assays. Body weight, rectal temperature and T4 concentration were lower in hypothyroid groups. When measurements of oxidative stress markers, redox environment, γ-glutamylcysteine synthetase and glutathione-S-transferase were determined, we observed that hypothyroid animals with TAA compensated better with oxidative damage than euthyroid animals treated with TAA. Furthermore, we measured reduced expressions of GADD34, caspase-12 and GRP78 and subsequently less hypothyroidism-induced cellular damage in hypothyroid animals. We conclude that hypothyroidism protects against hepatic damage caused by TAA because it reduces endoplasmic reticulum stress and changes to the redox environment.
authors.affiliation: Laboratorio de Neurobiología del Departamento de Fisiología. Escuela Nacional de Ciencias Biológicas, I.P.N. México, Mexico City, Mexico.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Blas-Valdivia
authors.affiliation: Laboratorio de Metabolismo I del Departamento de Fisiología.Escuela Nacional de Ciencias Biológicas, I.P.N. México, Mexico City, Mexico.
authors.forename: Edgar
authors.initials: E
authors.lastname: Cano-Europa
authors.affiliation: Laboratorio de Metabolismo I del Departamento de Fisiología.Escuela Nacional de Ciencias Biológicas, I.P.N. México, Mexico City, Mexico.
authors.forename: Yoalli
authors.initials: Y
authors.lastname: Martinez-Perez
authors.affiliation: Departamento de Morfología. Escuela Nacional de Ciencias Biológicas, I.P.N. Mexico City, Mexico.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lezama-Palacios
authors.affiliation: Laboratorio de Metabolismo I del Departamento de Fisiología.Escuela Nacional de Ciencias Biológicas, I.P.N. México, Mexico City, Mexico.
authors.forename: Margarita
authors.initials: M
authors.lastname: Franco-Colin
authors.affiliation: Laboratorio de Neurobiología del Departamento de Fisiología. Escuela Nacional de Ciencias Biológicas, I.P.N. México, Mexico City, Mexico. Electronic address: rocipn@yahoo.com.mx.
authors.forename: Rocio
authors.initials: R
authors.lastname: Ortiz-Butron
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D053454:Caspase 12 / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D065840:Protective Factors; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000943:Antigens, Differentiation; D053454:Caspase 12; D005978:Glutathione; D005982:Glutathione Transferase; D006360:Heat-Shock Proteins; D011518:Proto-Oncogene Proteins; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C489287:Ppp1r15a protein, rat; C506443:Casp12 protein, rat
keywords: Acute liver failure-model; Protective state; Reduced environment; Thyroid gland; Thyroidectomy