Abd-Elmawla Mai A, Elsamanoudie Nourhan M, Ismail Manal Fouad, Hammam Olfat Ali, El Magdoub Hekmat M
Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Biochemistry, Faculty of Pharmacy, Misr International University, Cairo, Egypt.
Int Immunopharmacol. 2024 Dec 25;143(Pt 3):113577. doi: 10.1016/j.intimp.2024.113577. Epub 2024 Nov 15.
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).
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.
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.
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.
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.
庆大霉素（GNT）是一种广谱抗生素，在重症患者中广泛使用。然而，GNT对肾近端小管有有害影响，可能导致急性肾损伤（AKI）。
本研究旨在通过调节TLR4/MyD88/NF-қB/IL-1β信号通路，研究TapSAKI、NEAT-1和miR-22-3p在GNT诱导的AKI中的相互作用。本研究还进一步探讨了甜菜红素（BET）在减轻GNT诱导的AKI中的作用。
除了在最后8天腹腔注射GNT（100mg/kg/天）外，连续28天经口给予BET（25mg/kg/天）。采用RT-PCR检测TapSAKI、NEAT-1和miR-22-3p基因表达。采用比色法检测血清肌酐（SCr）、尿素水平，采用ELISA技术检测肾损伤分子-1（KIM-1）、TLR4和IL-1β水平。此外，还进行了组织病理学检查。
本研究显示，在GNT诱导的AKI组中，TapSAKI和NEAT-1的表达显著上调，而miR-22-3p显著下调。这些非编码RNA的表达与TLR4/NF-қB/MyD88/IL-1β轴以及丙二醛和谷胱甘肽水平之间存在显著相关性。与GNT诱导的AKI组相比，BET预处理组使SCr、尿素和KIM-1水平恢复正常，TapSAKI和NEAT-1显著下调，miR-22-3p上调。此外，与未治疗的AKI大鼠相比，BET对TLR4/MyD88/NF-қB/IL-1β级联反应有明显抑制作用。此外，BET使氧化应激标志物恢复正常。
在长链非编码RNA TapSAKI、NEAT-1和微小RNA-22-3p的影响下，BET通过调节TLR4/MyD88/NF-қB/IL-1β信号通路降低了GNT对肾脏的毒性作用，从而抑制了氧化应激和炎症反应。
