Abstract
Background: Ischemia-Reperfusion Injury (IRI) is one of the major triggers of Acute Kidney Injury (AKI). AKI represents an important economic burden that is associated with high mortality and morbidity rates.
Aim of Study: This study focused on the role of poly (ADP-ribose) polymerase-1 (PARP-1) in acute renal ischemia-reperfusion injury in case of preconditioning with thyroid hormone.
Material and Methods: Forty adult male wistar albino rats were divided equally into; Group I: Sham-operated for renal IRI, Group II: Euthyroid rats subjected to IRI, Group III: PARP-1 inhibitor (3-AB) was administered to the IRI rats aiming to confirm the PARP-1 role in mediating the renal ischemic injury (IRI-3-AB). Group IV preconditioned rats with a single eltroxin dose (100ug/kg/ip) six hours before IRI (precond-IRI).
Results: PARP-1 inhibitor was associated with a significant improvement in the all measured renal function parameters, concomitant with reduced renal tissue inflammatory and oxidative stress markers and Apoptosis Inducing Factor (AIF) levels, indicating the intermediary role of PARP-1 in the renal ischemic injury.
The preconditioning with thyroid hormones resulted in a significant improvement in the renal functions (without elevation in the thyroid hormone level), via reduction in the inflammatory and oxidative stress markers induced by the IRI, this was confirmed by the histological assessment. The PARP-1, AIF and caspase-3 overexpression were aborted and the ATP level was preserved.
The correlations between PARP-1 and renal function parameters and the apoptotic markers may explain its contri-bution in the pathogenesis of renal IRI condition.
Conclusion: These results suggest an important role of the preconditioning with thyroid hormone in amelioration of the oxidative stress, inflammation and PARP-1 overactivation in the renal injury induced by IRI.