The Impact Of Resveratrol On The Interplay Between The Hippo And The microRNA 21/Programmed Cell Death 4 (PDCD-4) Signaling Pathways In Acetaminophen Induced Acute Renal Injury In Rats

Document Type : Original Article

Authors

1 Medical Biochemistry and Molecular Biology Department,Faculty of Medicine,Tanta University,Tanta,Egypt

2 Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine,Tanta University,Tanta,Egypt

3 Pharmacology Department, , Faculty of Medicine, Tanta University, Egypt

4 Anatomy & Embryology Department, Faculty of Medicine, Tanta University, Tanta, Egypt

5 Anatomy & Embryology Department, Faculty of Medicine, Tanta University

6 Physiology Department, Faculty of Medicine, Tanta University, Tanta, Egypt

7 Clinical and Chemical Pathology Department,Faculty of Medicine,Tanta University,Tanta,Egypt

8 Medical Biochemistry & Molecular Biology Department, Faculty of Medicine ,Tanta University,Tanta, Egypt

Abstract

Background: Resveratrol is a polyphenol with antioxidant properties. The study aims to clarify the resveratrol impact on acetaminophen-induced acute kidney injury in rats through targeting the hippo signaling pathway and the microRNA 21/ Programmed cell death 4 (PDCD-4) axis.
Methods: 24 male albino rats were enrolled into 3 groups, with 8 rats in each group. Control group received normal saline, once daily, for 7 days. Acetaminophen group has been treated with a single dose of acetaminophen (2g/Kg) orally 24 hours before being sacrificed. Resveratrol group was pretreated with resveratrol (30 mg/kg) for 7 days, before being given acetaminophen orally as single dose. The gene expression levels of PDCD - 4 and microRNA 21, and levels of yes-associated protein 1 (YAP1) were estimated in renal tissue. Immunohistochemical expression of BAX was determined. Blood urea, serum creatinine, malondialdehyde (MDA), and reduced glutathione (GSH)in renal tissue were assayed.
Results: Acetaminophen group displayed significant rise in the levels of MDA, YAP1,blood urea, serum creatinine, and BAX.PDCD-4 and microRNA 21 gene expression levels were elevated in acetaminophen group, in comparison with other groups, while resveratrol group showed significant decrease in the same parameters. Acetaminophen group displayed significant decrease in serum BCL2, and tissue GSH compared to other groups.
Conclusion: Resveratrol has a renoprotective efficacy through reducing oxidative stress, targeting the hippo signaling pathway effector YAP1, and the microRNA 21/PDCD-4 signaling pathway, decline of BAX which is pro-apoptotic, and elevation of BCL 2 which is anti-apoptotic.

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