Preconditioning with Triiodothyronine Improves the Clinical Signs and Acute Tubular Necrosis Induced by Ischemia/Reperfusion in Rats

BACKGROUND: Renal ischemia/reperfusion (I/R) injury is manifested by acute renal failure (ARF) and acute tubular necrosis (ATN). The aim of this study was to evaluate the effectiveness of preconditioning with 3, 3, 5 triiodothyronine (T(3)) to prevent I/R renal injury. METHODOLOGY/PRINCIPAL FINDINGS: The rats were divided into four groups: sham-operated, placebo-treated (SO-P), sham-operated T(3-) treated (SO- T(3)), I/R-injured placebo-treated (IR-P), and I/R-injured T(3)-treated (IR- T(3)) groups. At 24 h before ischemia, the animals received a single dose of T(3) (100 μg/kg). Renal function and plasma, urinary, and tissue variables were studied at 4, 24, and 48 h of reperfusion, including biochemical, oxidative stress, and inflammation variables, PARP-1 immunohistochemical expression, and ATN morphology. In comparison to the SO groups, the IR-P groups had higher plasma urea and creatinine levels and greater proteinuria (at all reperfusion times) and also showed: increased oxidative stress-related plasma, urinary, and tissue variables; higher plasma levels of IL6 (proinflammatory cytokine); increased glomerular and tubular nuclear PARP-1 expression; and a greater degree of ATN. The IR-T(3) group showed a marked reduction in all of these variables, especially at 48 h of reperfusion. No significant differences were observed between SO-P and SO-T(3) groups. CONCLUSIONS: This study demonstrates that preconditioning rats with a single dose of T(3) improves the clinical signs and ATN of renal I/R injury. These beneficial effects are accompanied by reductions in oxidative stress, inflammation, and renal PARP-1 expression, indicating that this sequence of factors plays an important role in the ATN induced by I/R injury.