Open AccessPreconditioning with Triiodothyronine Improves the Clinical Signs and Acute Tubular Necrosis Induced by Ischemia/Reperfusion in Rats
Author(s) -
C. Ferreyra,
Félix Vargas,
Isabel Rodrı́guez-Gómez,
Rocío Pérez-Abud,
Francisco O’Valle,
Antonio Osuna
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0074960
Subject(s) - medicine , creatinine , renal ischemia , endocrinology , acute tubular necrosis , oxidative stress , renal function , kidney , reperfusion injury , proinflammatory cytokine , ischemia , acute kidney injury , triiodothyronine , placebo , necrosis , inflammation , pathology , hormone , alternative medicine
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.