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 Ganal 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

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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.
Original languageEnglish
Article number104262
Number of pages9
JournalEnvironmental Toxicology and Pharmacology
Volume103
Early online date10 Sept 2023
DOIs
Publication statusPublished - 31 Oct 2023
Externally publishedYes

Keywords

  • hydroxytyrosol
  • Mi-RNA 25
  • Ox-LDL
  • NOX4
  • HO-1
  • FOXO3a

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