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

Abstract

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.

Potential activity of GIT-27 against renal ischemia reperfusion injury: an experimental study in male rats

“…According to our knowledge there was no data published Copyright © 2016 PCIJ 96 P a g e discussed the relationship renal ischemia reperfusion injury and effective role of GIT-27 on improved renal function following I/R model in rat. A number of published paper have investigated and confirmed that renal dysfunction during ischemia reperfusions related with inflammatory mediator's expression, including TNF-α and IL-1β [19]. Interestingly, we observed in this study that pretreatment with GIT-27 results in significantly reduction in cytokines with improvement in renal function.…”

“…It is important to create novel medications to protect kidney from IRI [17]. Previous studies reported that expression of inflammatory mediators (TNF-α, IL-18) was higher following renal injury [18,19]. The present study investigated the GIT-27 to improve the renal function following ischemia reperfusion injury.…”

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…Additional effects included attenuation of the acute inflammatory response and reduction of myocardial infarct size (290), and improvement of maximal perfusion potential of the hypertrophied myocardium surviving a myocardial infarction (291). However, other studies reported side effects (292,293) or failed to obtain positive results with DITPA in similar settings (294,295).…”

Preconditioning with Thyroid Hormones Improves Renal Functions Via Poly (ADP-Ribose) Polymerase-1 Reduction in a Rat Model of Renal Ischemia-Reperfusion Injury

“…However, unsuccessful administration of 3, 5diiodothyropropionic acid, 30min before renal IRI injury; may be due to short time course to exert preconditioning effect on oxidative stress [30] . PARP-1 activity and caspase-3 level were decreased in case of preconditioning with thyroid hormone as compared to IRI group either in acute renal IRI [4] or in the chronic kidney disease [31] .…”