Heme oxygenase-1 prevents hyperthyroidism induced hepatic damage via an antioxidant and antiapoptotic pathway.
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.


CONCLUSIONS
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.
Giriş
Murat
M
Department of Biochemistry, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey.
Erbil
Yeşim
Y
Depboylu
Bilge
B
Mete
Ozgür
O
Türkoğlu
Umit
U
Abbasoğlu
Semra Doğru
SD
Uysal
Müjdat
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000494:pharmacology*; D006980:Hyperthyroidism / Q000517:prevention & control*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000378:metabolism
D000975:Antioxidants; D016877:Oxidants; D011524:Protoporphyrins; D014284:Triiodothyronine; C017803:zinc protoporphyrin; D051547:Heme Oxygenase-1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3