A combined iron and thyroid hormone protocol suppresses ischemia–reperfusion injury in rat livers. Issue 33 (17th March 2015)

• Record Type: Journal Article
• Authors: Pedemonte, J. C.; Vargas, R.; Castillo, V.; Hodali, T.; Gutiérrez, S.; Tapia, G.; Castillo, I.; Videla, L. A.; Fernández, V.
• Is Part Of: RSC advances. Volume 5:Issue 33(2015)
• Page Start: 26209
• Page End: 26217
• Publication Date: 2015-03-17
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c4ra15863f
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Liver preconditioning (PC) against ischemia–reperfusion (IR) injury is attained by iron (Fe) or thyroid hormone (T3 ) administration. Abstract : Liver preconditioning (PC) against ischemia–reperfusion (IR) injury is attained by iron (Fe) or thyroid hormone (T3 ) administration. This study aimed to evaluate the PC effects of a combined Fe plus T3 protocol, characterized by a reduced period of Fe treatment and low T3 dosage, against ischemia (1 h)–reperfusion (20 h) injury. Male Sprague-Dawley rats were given Fe (two doses of 50 mg kg −1 at days 0 and 2), T3 (0.05 mg kg −1 at day 5), and subjected to a sham operation or IR at day 7. At this time, blood and liver samples were taken for analysis of serum aspartate (AST) and alanine (ALT) aminotransferases and hepatic histology, glutathione (GSH), protein carbonyl, and 8-isoprostane contents, protein levels of nuclear factor E2-related factor 2 (Nrf2) (western blot), nuclear factor-κB (NF-κB) DNA binding (ELISA), and mRNA expression of glutamate-cysteine ligase-c (GCLC) and haptoglobin (real-time quantitative PCR). IR enhanced serum AST and ALT levels with drastic changes in liver morphology, significant enhancement in protein carbonyl/GSH ratios and 8-isoprostane content, diminution in nuclear Nrf2 content and in NF-κB DNA binding, without changes in GCLC and haptoglobin mRNA expression. These IR-induced changes were not modified by an individual Fe or T3 pre-treatment, but suppressed by the combined Fe plus T3 protocol with increased GCLC and haptoglobin expression. In conclusion, a combined Fe plus T3 protocol suppresses IR liver injury, a novel PC strategy that is related to normalization of the oxidative stress status, Nrf2 and NF-κB activation, and associated GCLC and haptoglobin upregulation.