Effect of Xanthenone Versus Irisin in Alleviating Renal Ischemic Reperfusion Injury through Modifying the PI3K/AKT/eNOS and TLR-4/NFkB Pathways | ||||
Bulletin of Egyptian Society for Physiological Sciences | ||||
Volume 44, Issue 2, April 2024, Page 83-105 PDF (2.17 MB) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/besps.2024.256207.1160 | ||||
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Authors | ||||
Eman Kolieb 1; Rehab Ahmed Ahmed El-shaer 2; Shymaa A. Maher 3; Dina A. Ali 4; Amal M. A. Hammada 5; Marwa Mahmoud Awad 2 | ||||
1Physiology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt | ||||
2Physiology Department, Faculty of Medicine, Tanta University, Tanta 31511, Egypt | ||||
3Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt | ||||
4Clinical Pharmacology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt | ||||
5Anatomy Department, Faculty of Medicine, Tanta University, Tanta 31511, Egypt; | ||||
Abstract | ||||
Ischemic reperfusion injury (IRI) in the kidney is a common cause of acute-kidney-injury. Our aim is to compare the effects of Xanthenone /Irisin on alleviating inflammation, cell apoptosis and oxidative stress injury in kidney IRI via modulating the PI3K/Akt/eNOS and TLR4-NFkB pathways. 32 male rats were equally divided into groups: Control, IR, IR treated with (i.v) Xanthenone (10mg/kg), IR treated with (i.p) Irisin (100 µg/kg). Renal functions, blood pressure, renal tissue ACE2, Ang 1-7, inflammatory, oxidative stress and apoptotic markers were evaluated. Also, PI3K/AKT/eNOS and TLR-4 relative mRNA levels in renal tissue were assessed. Also, the protein concentration of pAKT, eNOS, histomorphological, and immunohistochemical analysis were done. In IR group, renal function tests, blood pressure, and apoptotic parameters were elevated. ACE2 and Ang (1-7) tissue levels, relative gene expression of PI3K/AKT/eNOS and TLR-4, the protein concentration of pAKT and eNOS, histomorphological and immunohistochemical analysis of NFkB in renal tissue were all distorted in IR group. However, Xanthenone and Irisin treatments improved renal function, inflammation, and oxidative stress through PI3K/AKT/eNOS and TLR-4/ NFĸB pathway. Moreover, Xanthenone acts through ACE2/Ang (1-7) pathway, while Irisin acts mainly through PI3K/AKT/eNOS and TLR4/NFkB pathway. This may increase the potential for combined Xanthenone and Irisin therapy during conditions of AKI. | ||||
Keywords | ||||
Renal Ischemic/reperfusion; Xanthenone; Irisin; ACE2; Ang II | ||||
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