Effect of 3,5-diiodothyropropionic Acid (DITPA) on Renal Ischemia/ Reperfusion Injury in a Mouse Model

Abstract

Introduction: Acute renal failure (ARF) is an important clinical problem with a high mortality and morbidity. Ischemia/reperfusion (I/R) was considered one of the primary causes of ARF. Inflammatory process is thought to be the major mechanism that contribute to I/R injury. There are evidences of the importance of thyroid hormone (TH) in the response of the myocardium to ischemic stress and cardiac remodeling following myocardial infarction. 3,5-diiodothyropropionic acid (DITPA) is a synthetic TH analogue with a low metabolic activity. Also DITPA have evidences of improving effects on I/R in heart through modulation of cellular signaling in response to ischemic stress and this modulation may be beneficial in protection from renal I/R damage. Objectives: The objective of present study was to assess the effects of DITPA onrenal I/R injury and the resulted kidney dysfunction in a mouse model. Materials and Methods: A total of 18 Adult males of Swiss albino mice were randomized to three groups: I/R group (n=6), mice underwent 30 minute bilateral renal ischemia and 48 hr reperfusion. Sham group (n=6), mice underwent same anesthetic and surgical procedures except for ischemia induction. DITPA treated group: (n=6), I/R + DITPA (3.75 mg/kg) by intraperitoneal injection.After the end of reperfusion phase mice were sacrificed, blood samples were collected directly from the heart for determination of serum IL-18, IL-6, urea and Creatinine. Both kidney were excised, the right one homogenized for oxidative stress parameters (MDA and GSH) measurements and the left kidney fixed in formalin for histological examination.Results: Serum IL-18, IL-6, urea and Creatinine, kidney MDA levels and scores of histopathological changes were significantly (P< 0.05) elevated in I/R group as compared with that of sham group. Kidney GSH level was significantly (P < 0.05) decreased in I/R group as compared with that of sham group. DITPA caused non-significant (P>0.05) changes in levels of all study parameters as compared with that of I/R group. Conclusion: The results of the present study show that DITPA insignificantly ameliorated kidney damage resulted from I/R.