Combination therapy with melatonin, stem cells and extracellular vesicles is effective in limiting renal ischemia-reperfusion injury in a rat model

Rasha Zahran; Asmaa Ghozy; Sanad S Elkholy; Fathy El-Taweel; Mohammed Abu El-Magd

doi:10.1111/iju.14345

Combination therapy with melatonin, stem cells and extracellular vesicles is effective in limiting renal ischemia-reperfusion injury in a rat model

Int J Urol. 2020 Nov;27(11):1039-1049. doi: 10.1111/iju.14345. Epub 2020 Aug 14.

Authors

Rasha Zahran¹, Asmaa Ghozy¹, Sanad S Elkholy², Fathy El-Taweel³, Mohammed Abu El-Magd⁴

Affiliations

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.

PMID: 32794300
DOI: 10.1111/iju.14345

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.

Keywords: exosomes; ischemia-reperfusion injury; melatonin; mesenchymal stem cells; oxidative stress.

MeSH terms

Animals
Apoptosis
Female
Kidney
Kidney Diseases*
Melatonin* / pharmacology
Melatonin* / therapeutic use
Mesenchymal Stem Cells*
Oxidative Stress
Rats
Reperfusion Injury* / prevention & control

Substances

Melatonin