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Possible mechanisms for the renoprotective effects of date palm fruits and seeds extracts against renal ischemia/reperfusion injury in rats - 27/10/20

Doi : 10.1016/j.biopha.2020.110540 
Mansour A. Alghamdi a, b, Abdelaziz M. Hussein c, , Laith N. AL-Eitan d, e, Eman Elnashar a, f, Ahmed Elgendy c, Asim M. Abdalla a, Seham Ahmed g, Wael A. Khalil h
a Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia 
b Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia 
c Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt 
d Department of Applied Biological Science, Jordan University of Science and Technology, Irbid 22110, Jordan 
e Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan 
f Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt 
g Department of Organic Chemistry, Faculty of Science, Zagazig University, Zagazig 35621, Egypt 
h Department of Animal Production, Faculty of Agriculture, Mansoura University, Mansoura 35516, Egypt 

Corresponding author.

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Graphical abstract

Mechanisms involved the pathogenesis of renal I/R injury and possible renoprotective mechanisms of palm date extracts. Renal ischemia for 45-min caused loss of renal tubular epithelial cells by necrosis and apoptosis via upregulation of the free oxygen radicals, inflammatory cytokine TNF-α. Also, it enhanced the expression of nrf2 to increase the resistance of renal tubular epithelia cells to withstand oxidative stress and increases the expression of TGF-β which help renal fibrosis. Renal fibrosis and acute tubular necrosis result in impairment of the renal functions. Palm dates might exert their renoprotective effects via attacking the production of free radicals, upregulation of Nrf2 and downregulation of TNF-α and TGF-β.




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Highlights

Renal ischemia for 45 min caused significant deterioration in kidney functions and morphology.
Renal I/R was associated with enhanced oxidative stress and upregulation of TNF-α, TGF-β, Caspase-3 and Nrf2 in kidney tissues.
Pre-treatment with palm date fruit and seed extracts significantly improved the kidney functions and morphology which might be due upregulation of Nrf2, downregulation of TNF-α, TGF-β and caspase-3 and attenuation of redox state.

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Abstract

Purpose

This work investigates the possible renoprotective effects of date palm fruits and seeds extract against renal ischemia and their underlying mechanisms.

Methods

108-Sprague Dawle male rats were randomly allocated into 6 equal groups differently receiving aqueous or methanolic fruit and seed extracts. Assay of serum creatinine, BUN and TNF-α, morphological examination of the left kidney, markers of the redox state (MDA, CAT, and GSH), the expression of TNFα and Nrf2 genes at the level of mRNA, the expression of caspase-3 and TGF-β proteins by immunohistochemistry were performed.

Results

45-min renal I/R caused significant deterioration of kidney functions (increase in serum creatinine and BUN) and morphology (P < 0.001) and significant reduction in CAT activity and GSH levels with significant increase in serum TNF-α and MDA concentration and the expression of Nrf2, caspase-3, TNF-α, and TGF-β in kidney tissues. Pre-treatment with either date palm fruit or seed extracts significantly improved kidney functions and morphology (P ≤ 0.001) with a significant increase in the expression of Nrf2 and CAT activity, and GSH concentration and a reduction in serum TNF-α and expression of caspase-3, TNF-α, and TGF-β (P < 0.001).

Conclusions

Administration of date palm extracts exhibited a renoprotective effect against renal I/R injury.This renoprotective action might be due to their antioxidants, anti-apoptotic and anti-inflammatory actions. Moreover, aqueous fruit extracts offered powerful renoprotective effect than aqueous seed extracts, and aqueous fruit and seed extracts were generally more effective than methanolic extracts.

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Keywords : Kidney diseases, Phoeniceae, Creatinine, Caspase3, Immunohistochemistry, Renal ischemia


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