Heme Oxygenase-1 Prevents Hyperthyroidism Induced Hepatic Damage via an Antioxidant and Antiapoptotic Pathway

• Published in: The Journal of surgical research Vol. 164; no. 2; pp. 266 - 275
• Main Authors: Giriş, Murat, M.Sc, Erbil, Yeşim, M.D, Depboylu, Bilge, M.D, Mete, Özgür, M.D, Türkoğlu, Ümit, M.D, Abbasoğlu, Semra Doğru, M.D, Uysal, Müjdat, M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-12-2010; Elsevier
• Subjects: Alanine Transaminase - blood; Animals; Antioxidants - metabolism; apoptosis; Aspartate Aminotransferases - blood; Biological and medical sciences; Blotting, Western; Caspase 3 - metabolism; Cytoplasm - drug effects; Cytoplasm - metabolism; Endocrinopathies; General aspects; Heme Oxygenase-1 - pharmacology; heme-oxygenase; hyperthyroidism; Hyperthyroidism - prevention & control; Immunohistochemistry; In Situ Nick-End Labeling; liver damage; Male; Medical sciences; Mitochondria - drug effects; Mitochondria - metabolism; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oxidants - metabolism; Prevention and actions; Protoporphyrins - pharmacology; Public health. Hygiene; Public health. Hygiene-occupational medicine; Rats; Rats, Wistar; Surgery; Thyroid. Thyroid axis (diseases); Triiodothyronine - metabolism; heme-oxygenase; apoptosis; hyperthyroidism; liver damage; Endocrinopathy; Digestive system; Enzyme; Liver; Hyperthyroidism; Thyroid diseases; Heme oxygenase (decyclizing); Hepatic disease; Antioxidant; Medicine; Prevention; Antiapoptotic agent; Treatment; Cell death; Surgery; Heat shock protein; Digestive diseases; Oxidoreductases; Lesion; Apoptosis
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2009.04.013

Background The exact pathogenesis of hepatic dysfunction in hyperthyroidism is still unknown. We aimed to investigate the pathogenesis of liver dysfunction caused by hyperthyroidism through inducing heme oxygenase-1 (HO-1) expression, which has antioxidant and anti-apoptotic properties. Methods Rats were divided into six groups: untreated (group 1), treated with zinc protoporphyrin (ZnPP) (group 2), treated with hemin (group 3), treated with tri-iodothyronine (T3) (group 4), treated with T3 and ZnPP (group 5), and treated with T3 and hemin (group 6). After 22 d, oxidative stress and antioxidant enzymes and the expression of HO-1, mitochondrial permeability transition, cytochrome c , Bax, Bcl-2, caspase-3, caspase-8, and caspase-3 activity, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay were examined. Results Hyperthyroidism induced oxidative stress of liver tissue was ameliorated by HO-1 induction. Administration of hemin (HO-1 inducer) increased Bcl-2 expression. Decreased expression of cytochrome c was accompanied by a decrease in caspase-3, caspase-8, Bax expression, and caspase-3 activity. The apoptotic activity and oxidative damage were found to be increased by the administration of ZnPP (HO-1 inhibitor). Immunohistochemistry findings supported these results. Conclusion HO-1 induction plays a protective role in the pathogenesis of the liver dysfunction in hyperthyroidism. This effect is dependent on modulation of the antiapoptotic and antioxidative pathways by HO-1 expression.