Rasha Zahran1, Asmaa Ghozy1, Sanad S Elkholy2, Fathy El-Taweel3, Mohammed Abu El-Magd4. 1. Department of Chemistry (Biochemistry Division), Faculty of Science, Damietta University, Damietta, Egypt. 2. Department of Physiology, Faculty of Medicine, Kafrelsheikh University, Kafr El-Shaikh, Egypt. 3. Department of Chemistry, Faculty of Science, Damietta University, Damietta, Egypt. 4. Department of Anatomy, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Shaikh, Egypt.
Abstract
OBJECTIVE: To evaluate the therapeutic value of melatonin, mesenchymal stem cells and their extracellular vesicles, exosomes, on renal ischemia-reperfusion. METHODS: 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. RESULTS: 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 lymphoma 2-associated X protein, and higher B-cell lymphoma 2 genes/proteins); and inhibition of kidney inflammatory and damage markers (tumor necrosis alpha, interleukin-1β, nuclear factor kappa B, kidney injury molecule-1, IL-18, matrix metalloproteinase 9, neutrophil gelatinase-associated lipocalin). The improvement order was (highest to lowest): melatonin + exosomes, melatonin + mesenchymal stem cells, exosomes, mesenchymal stem cells and melatonin group. CONCLUSIONS: 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.
OBJECTIVE: To evaluate the therapeutic value of melatonin, mesenchymal stem cells and their extracellular vesicles, exosomes, on renal ischemia-reperfusion. METHODS: 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. RESULTS: 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 lymphoma 2-associated X protein, and higher B-cell lymphoma 2 genes/proteins); and inhibition of kidney inflammatory and damage markers (tumor necrosis alpha, interleukin-1β, nuclear factor kappa B, kidney injury molecule-1, IL-18, matrix metalloproteinase 9, neutrophil gelatinase-associated lipocalin). The improvement order was (highest to lowest): melatonin + exosomes, melatonin + mesenchymal stem cells, exosomes, mesenchymal stem cells and melatonin group. CONCLUSIONS: 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.
Authors: Zainab Ali Alnfakh; Dhefaf Hameed Al-Mudhafar; Rana Talib Al-Nafakh; Abdullah Elttayef Jasim; Najah Raiesh Hadi Journal: J Med Life Date: 2022-06