AUTHOR=Alqahtani Leena S. , Alosaimi Manal E. , Abdel-Rahman Mohamed Amany , Abd-Elhakim Yasmina M. , Khamis Tarek , Noreldin Ahmed E. , El-Far Ali H. , Alotaibi Badriyah S. , Hakami Mohammed Ageeli , Dahran Naief , Babteen Nouf A. 

TITLE=Acrylamide-targeting renal miR−21a−5p/Fibrotic and miR122-5p/ inflammatory signaling pathways and the role of a green approach for nano-zinc detected via in silico and in vivo approaches

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1413844

DOI=10.3389/fphar.2024.1413844

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Any disruption in renal function can have cascading effects on overall health. Understanding how a heat-born toxicant like acrylamide (ACR) affects kidney tissue is vital for realizing its broader implications for systemic health.</p><p><bold>Methods:</bold> This study investigated the ACR-induced renal damage mechanisms, particularly focusing on the regulating role of miR-21a-5p/fibrotic and miR-122-5p/inflammatory signaling pathways via targeting Timp-3 and TP53 proteins in an <italic>In silico</italic> preliminary study. Besides, renal function assessment, oxidative status, protein profile, and the expression of renal biomarkers (Timp-1, Keap-1, Kim-1, P53, TNF-α, Bax, and Caspase3) were assessed in a 60-day experiment. The examination was additionally extended to explore the potential protective effects of green-synthesized zinc oxide nanoparticles (ZNO-MONPs). A four-group experiment including control, ZNO-MONPs (10 mg/kg b.wt.), ACR (20 mg/kg b.wt.), and ZNO-MONPs + ACR was established encompassing biochemical, histological, and molecular levels. The study further investigated the protein-binding ability of ZNO and MONPs to inactivate caspase-3, Keap-1, Kim-1, and TNFRS-1A.</p><p><bold>Results:</bold> ZNO-MONPs significantly reduced ACR-induced renal tissue damage as evidenced by increased serum creatinine, uric acid, albumin, and oxidative stress markers. ACR-induced oxidative stress, apoptosis, and inflammationare revealed by biochemical tests, gene expression, and the presence of apoptotic nuclei microscopically. Also, molecular docking revealed binding affinity between ACR-BCL-2 and glutathione-synthetase, elucidating the potential mechanisms through which ACR induces renal damage. Notably, ZNO-MONPs revealed a protective potential against ACR-induced damage. Zn levels in the renal tissues of ACR-exposed rats were significantly restored in those treated with ACR + ZNO-MONPs. In conclusion, this study establishes the efficacy of ZNO-MONPs in mitigating ACR-induced disturbances in renal tissue functions, oxidative stress, inflammation, and apoptosis. The findings shed light on the potential renoprotective activity of green-synthesized nanomaterials, offering insights into novel therapeutic approaches for countering ACR-induced renal damage.</p>