Abstract
To evaluate the therapeutic value of melatonin, mesenchymal stem cells and their extracellular vesicles, exosomes, on renal ischemia-reperfusion. Female albino rats (n=64) were divided into eight groups (n=8 per group): control, sham (only laparotomy), renal ischemia-reperfusion (renal ischemia-reperfusion+phosphate-buffered saline), melatonin (renal ischemia-reperfusion+melatonin), mesenchymal stem cells (renal ischemia-reperfusion+mesenchymal stem cells), exosomes (renal ischemia-reperfusion+exosomes), melatonin+mesenchymal stem cells (renal ischemia-reperfusion+melatonin+mesenchymal stem cells) and melatonin+exosomes (renal ischemia-reperfusion+melatonin+exosomes). After the establishment of the renal ischemia-reperfusion model, rats in each group were bilaterally injected once with either mesenchymal stem cells or exosomes in both renal arteries during reperfusion. Notable improvement of renal ischemia-reperfusion was obtained after different treatments, as evidenced by a lower histopathological score of kidney injury; decreased serum levels of urea, creatinine and retinol-binding protein; reduced lipid peroxidation marker malondialdehyde; increased superoxide dismutase and catalase activities; reduced apoptosis (lower DNA damage and B-cell lymphoma2-associated Xprotein, and higher B-cell lymphoma2 genes/proteins); and inhibition of kidney inflammatory and damage markers (tumor necrosis alpha, interleukin-1β, nuclear factor kappaB, kidney injury molecule-1, IL-18, matrix metalloproteinase9, neutrophil gelatinase-associated lipocalin). The improvement order was (highest to lowest): melatonin+exosomes, melatonin+mesenchymal stem cells, exosomes, mesenchymal stem cells and melatonin group. Our data suggest a potential therapeutic effect of combined therapy with melatonin, mesenchymal stem cells and their exosomes to minimize renal ischemia-reperfusion injury in rats.
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