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.

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.