Current Issues of Pharmacy and Medical Sciences

Nfe2 expression in the hyperthyroid rat heart receiving doxorubicin

Annales UMCS, Sectio DDD, Pharmacia, Vol. XXIV, N 3, 3

JAROSŁAW DUDKA1, AGNIESZKA KORGA1, RENATA GIEROBA1,
BEATA WALCZYNA2, SŁAWOMIR MANDZIUK3,
KATARZYNA DAWIDEK-PIETRYKA4, FRANCISZEK BURDAN5

Independent Medical Biology Unit, Medical University of Lublin, Poland

Department of Clinical Pathomorphology, Medical University of Lublin, Poland

Department of Pneumology Oncology and Alergology, Medical University of Lublin, Poland 

Lloyds Pharmacy, Sheffield, United Kingdom

Department of Human Anatomy Medical University of Lublin, Poland

Abstract

The most evidence suggests that the major cause of doxorubicin (DOX) cardiotoxicity is reactive oxygen species and consequently oxidative stress. The accumulation of oxidative damages leading to mitochondrial dysfunction results in contractility disorders. In a cell adaptive process against oxidative stress, the transcription factor Nrf2 (Nfe2) plays a crucial role by stimulating expression of genes controlling synthesis of enzymes taking part in oxidative defence and red-ox equilibrium, e.g. glucose-6-phosphate dehydrogenase, phosphogluconate dehydrogenase and malic enzyme. Expression of genes responsible for the synthesis of these enzymes is controlled by iodothyronine hormones. These facts lead to an assumption that the impact of anthracyclines on oxidative stress may differ in hyperthyroid and euthyroid individuals. In these studies first of all we tested the hypothesis that symptoms of oxidative stress may be evident long time since last dose of DOX and if hypothyreosis may change myocardium antioxidative response in rats which received DOX. There was no statistical difference in Nfe2 expression in hearts of rats after doxorubicin administrations (group of DOX) versus controls. In this group there were no statistical differences in cardiac NADPH and total mitochondrial glutathione concentrations and GSH/GSSG ratio comparing to the controls. Moreover, any changes in all tested parameters were observed between DOX vs. DOX+4T4. We concluded that after three weeks since last doxorubicin administration there were no significant signs of oxidative stress in the heart, and that in our study conditions there was no interaction of DOX and thyroxin referring to oxidative stress in the myocardium.

Files to download

Keywords

Doxorubicin, thyroxin, hyperthyreosis, Nfe2 (Nrf2) expression, NADPH, glutathione, oxidative stress

Calendar

April 2021

Mon Tue Wed Thu Fri Sat Sun
      01 02 03 04
05 06 07 08 09 10 11
12 13 14 15 16 17 18
19 20 21 22 23 24 25
26 27 28 29 30