Enhanced protection against renal ischemia-reperfusion injury with combined melatonin and exendin-4 in a rodent model

We tested the hypothesis that combined treatment with melatonin, an anti-oxidant, and exendin-4, an anti-inflammatory agent, was superior to either alone for protecting the kidney from ischemia–reperfusion (IR) injury. Male adult Sprague-Dawley rats (n=40) were equally divided into group 1 (sham-operated control), group 2 (IR only, IR=1h/72h), group 3 (IR–exendin-4, 10 µg/kg at 30 min, 24 h, 48 h after IR procedure), group 4 (IR–melatonin, i.p. 50 mg at 30 min, then 20 mg at 6 and 18 h after IR procedure), and group 5 (combined IR–exendin-4–melatonin). All animals were sacrificed by 72 h after IR/sham procedure. The results showed that the kidney injury score, plasma creatinine, and blood urea nitrogen (BUN) levels were highest in group 2 and lowest in group 1, significantly higher in groups 3 and 4 than those in group 5 and significantly higher in group 3 than those in group 4 (all p < 0.001). The protein expressions of inflammatory (toll-like receptor 4, inducible nitric oxide synthase, interleukin-1β), apoptotic (mitochondrial Bax, cleaved caspase-3 and poly(ADP-ribose) polymerase, p53), podocyte integrity (E-cadherin, P-cadherin), and cell survival (phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin) biomarkers, as well the podocyte dysfunction biomarkers (Wnt1/Wnt4/β-catenin) displayed a pattern identical to that of creatinine level among the five groups (all p < 0.001). Microscopic findings demonstrated th...
Source: Experimental Biology and Medicine - Category: Research Authors: Tags: Physiology Source Type: research