Effects of thyroid hormone analogue and a leukotrienes pathway-blocker on renal ischemia/reperfusion injury in mice

[摘要] BackgroundAcute renal failure (ARF) is an important clinical problem with a high mortality and morbidity. One of the primary causes of ARF is ischemia/reperfusion (I/R). Inflammatory process and oxidative stress are thought to be the major mechanisms causing I/R. MK-886 is a potent inhibitor of leukotrienes biosynthesis which may have anti-inflammatory and antioxidant effects through inhibition of polymorphonuclear leukocytes (PMNs) infiltration into renal tissues. 3, 5-diiodothyropropionic acid (DITPA) have evidences of improving effects on I/R in heart through modulation of cellular signaling in response to ischemic stress. The objective of present study was to assess the effects of MK-886 and DITPA on renal I/R injury.MethodsA total of 24 Adult males of Swiss albino mice were randomized to four 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. MK-886-treated group: (n = 6), I/R + MK-886 (6 mg/kg) by intraperitoneal injection. 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 TNF-a, 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.ResultsSerum TNF-α, 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. MK-886 treated group has significantly (P < 0.05) lowered levels of all study parameters except for GSH level which was significantly (P < 0.05) higher as compared with that of I/R group. DITPA caused non-significant (P > 0.05) changes in levels of all study parameters as compared with that of I/R group.ConclusionThe results of the present study show that MK-886 significantly ameliorated kidney damage that resulted from I/R. For DITPA, as its administration might not be successful, administration using a different protocol may give different effects on I/R.

[发布日期] 2011-12-23

[关键词] Sham Group;Montelukast;Ischemia Induction;Renal Pedicle;Total Severity Score