Modulation of mi-RNA25/Ox-LDL/NOX4 signaling pathway by polyphenolic compound Hydroxytyrosol as a new avenue to alleviate cisplatin-induced acute kidney injury, a mechanistic study in rats

Mohamed Gamal El-Din Ewees; Raha Orfali; Enas Ezzat Rateb; Hossam M Hassan; Wael N Hozzein; Dalal Hussien M Alkhalfah; Haidy Tamer Abo Sree; Fatema El-Zahraa S Abdel Rahman; Mostafa E Rateb; Nesreen Ishak Mahmoud

doi:10.1016/j.etap.2023.104262

Modulation of mi-RNA25/Ox-LDL/NOX4 signaling pathway by polyphenolic compound Hydroxytyrosol as a new avenue to alleviate cisplatin-induced acute kidney injury, a mechanistic study in rats

Environ Toxicol Pharmacol. 2023 Oct:103:104262. doi: 10.1016/j.etap.2023.104262. Epub 2023 Sep 10.

Affiliations

¹ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef 11787, Egypt. Electronic address: Mohammed.gamal@nub.edu.eg.
² Department of Pharmacognosy, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: rorfali@ksu.edu.sa.
³ Department of Physiology, Faculty of Medicine, Beni-Suef University, Beni-Suef 62521, Egypt. Electronic address: enas_omyahya@med.bsu.edu.eg.
⁴ Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 11787, Egypt. Electronic address: hossam.mokhtar@nub.edu.eg.
⁵ Botany and Microbiology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. Electronic address: Wael.hozzein@bsu.edu.eg.
⁶ Department of Biology. College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia. Electronic address: dalal.alkhalifah@puu.edu.sa.
⁷ Department of Basic Sciences Department, Biochemistry, Faculty of Oral and Dental Medicine, Nahda University, Beni-Suef 11787, Egypt. Electronic address: Haidy.tamer@nub.edu.eg.
⁸ Department of Basic Sciences Department, Physiology, Faculty of Oral and Dental Medicine, Nahda University, Beni-Suef 11787, Egypt. Electronic address: Fatma.sabry@nub.edu.eg.
⁹ School of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK. Electronic address: Mostafa.Rateb@uws.ac.uk.
¹⁰ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef 11787, Egypt. Electronic address: Nesr_pharma@yahoo.com.

PMID: 37699441
DOI: 10.1016/j.etap.2023.104262

Abstract

Acute kidney injury (AKI) caused by Cis is considered one of the most severe adverse effects, which restricts its use and efficacy. This study seeks to examine the potential reno-protective impact of phenolic compound Hydroxytyrosol (HT) against Cis-induced AKI and the possible involvement of the mi-RNA25/Ox-LDL/NOX4 pathway elucidating the probable implicated molecular mechanisms. Forty rats were placed into 5 groups. Group I received saline only. Group II received Cis only. Group III, IV, and V received 20, 50, and 100 mg/kg b.w, of HT, respectively, with Cis delivery. NOX4, Ox-LDL, and gene expression of mi-RNA 25, TNF-α, and HO-1 in renal tissue were detected. HT showed reno-protective effect and significantly upregulated mi-RNA 25 and HO-1 as well as decreased the expression of NOX4, Ox-LDL, and TNF-α. In conclusion, HT may be promising in the fight against Cis-induced AKI through modulation of mi-RNA25/Ox-LDL/NOX4 pathway.

Keywords: HO-1 and FOXO3a; Hydroxytyrosol; Mi-RNA 25; NOX4; Ox-LDL.