Protective effect of thyroid hormone (3,5,3-triiodothyronine) on renal ischemia-reperfusion injury in mouse model

Abstract

Introduction Preconditioning is a strategy to prevent ischemia-reperfusion (I/R) injury by causing transient ischemia or increases in oxygen demand, thus resulting in protective actions in tissues and cells. 3,5,3-triiodothyronine(T3) was found to reduce cardiac or hepatic I/R injury in animal models when preconditioned 48 hours in advance. The purpose of this study was to evaluate the protective effects of T3 preconditioning on renal I/R injury with different interval of time, including a short period of time before I/R injury. Methods In male C57BL/6 mice, renal warm I/R injury was induced by temporary ligation of bilateral renal pedicle for 45 minutes followed by reperfusion period of 24 hours. Preconditioning with T3 was performed 24 or 6 hours before or at the time of I/R injury. Histologic tubular injury, expressions of proinflammatory markers, activities of antioxidative enzymes, and expressions of nitric oxide synthase (NOS) were evaluated. Results In histologic exam, tubular injury was significantly reduced in mice preconditioned with T3 6 hours before I/R injury. The levels of proinflammatory cytokines in renal tissue were decreased with T3-preconditioning 6 hours before or at the time of I/R injury. The levels of glutathione (GSH) were definitely increased in all treatment groups. The activities of superoxide dismutase (SOD) did not show statistically significant changes, but had an increased tendency in preconditioning 24 or 6 hours before I/R injury. Expressions of neuronal NOS (nNOS) was significantly increased in all treatment groups, especially in mice preconditioned with T3 6 hours before or at the time of I/R injury. However, inducible NOS (iNOS) and endothelial (eNOS) were significantly decreased when mice were preconditioned with T3 6 hours before or at the time of I/R injury. Conclusions Preconditioning with T3 in a short interval of time before I/R injury had a significant protective effect on renal warm I/R injury. It may be an applicable therapeutic protocol for deceased donor kidney transplantation in clinical practice.