The interplay of TapSAKI and NEAT-1 as potential modulators in gentamicin-induced acute kidney injury via orchestrating miR-22-3p/TLR4/MyD88/NF-қB/IL-1 β milieu: Novel therapeutic approach of Betanin.

Autor: Abd-Elmawla MA; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: mei.abdelmawla@pharma.cu.edu.eg., Elsamanoudie NM; Department of Biochemistry, Faculty of Pharmacy, Misr International University, Cairo, Egypt., Ismail MF; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt., Hammam OA; Department of Pathology, Theodor Bilharz Research Institute, Giza, Egypt., El Magdoub HM; Department of Biochemistry, Faculty of Pharmacy, Misr International University, Cairo, Egypt.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 25; Vol. 143 (Pt 3), pp. 113577. Date of Electronic Publication: 2024 Nov 15.
DOI: 10.1016/j.intimp.2024.113577
Abstrakt: Introduction: Gentamicin (GNT) is a broad-spectrum antibiotic that is widely prescribed in critically ill patients. However, GNT exerts deleterious effects on renal proximal tubules which could predispose to acute kidney injury (AKI).
Aim: The study aimed to investigate the interplay of TapSAKI, NEAT-1, and miR-22-3p in GNT-induced AKI via modulating the TLR4/MyD88/NF-қB/IL-1β trajectory. The study was extended to show the role of betanin (BET) in alleviating GNT-induced AKI.
Methods: BET (25  mg/kg/day) was administered via oral route for 28 consecutive days in addition to GNT (100  mg/kg/day) i.p. during the last 8 days. TapSAKI, NEAT-1, and miR-22-3p gene expressions were measured using RT-PCR. The levels of SCr, urea were measured using colorimetric assay, whereas KIM-1, TLR4, and IL-1β were measured using ELISA technique. Additionally, histopathological examinations were done.
Results: The present study revealed that the expression of TapSAKI and NEAT-1 were significantly upregulated in GNT-induced AKI group, whereas miR-22-3p was significantly downregulated. There were significant associations between the expression of these non-coding RNAs and TLR4/NF-қB/MyD88/IL-1β axis as well as malondialdehyde and glutathione levels. Favorably, BET pretreated group normalized the levels of SCr, urea, and KIM-1 and showed a significant downregulation of TapSAKI and NEAT-1 and upregulation of miR-22-3p compared with GNT-induced AKI group. Furthermore, BET showed a marked inhibition of TLR4/MyD88/NF-қB/IL-1β cascade compared with non-treated AKI rats. Moreover, BET normalized oxidative stress markers.
Conclusion: BET reduced GNT's toxic effects on kidneys through modulating TLR4/MyD88/NF-қB/IL-1β signaling pathway under the influence of lncRNAs TapSAKI, NEAT-1, and miRNA-22-3p, which consequently suppress oxidative stress and inflammation.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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