Evidence mapPaperPMID 42116184Full record

ArticleJournal of translational medicine2026

Paraxanthine and azilsartan attenuate gentamicin-induced renal fibrosis via modulation of TGF-β1/Smad3/7 signaling and miRNA-21/miRNA-200b expression.

Nany Saad Rizk El-Adwy, Nahla E El-Ashmawy, Ghada M Al-Ashmawy, Naglaa F Khedr

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Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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4 authors.

Nany Saad Rizk El-AdwyDepartment of Biochemistry, Faculty of Pharmacy, Tanta University, El-Geish Street, Medical Campus, Tanta, 31527, Egypt.
Nahla E El-AshmawyDepartment of Biochemistry, Faculty of Pharmacy, Tanta University, El-Geish Street, Medical Campus, Tanta, 31527, Egypt.
Ghada M Al-AshmawyDepartment of Biochemistry, Faculty of Pharmacy, Tanta University, El-Geish Street, Medical Campus, Tanta, 31527, Egypt.
Naglaa F KhedrDepartment of Biochemistry, Faculty of Pharmacy, Tanta University, El-Geish Street, Medical Campus, Tanta, 31527, Egypt. naglaa.khedr@pharm.tanta.edu.eg.ORCID 0000-0003-4539-8940

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6 · The paper itself

Abstract

backgroundRenal fibrosis is a key contributor to chronic kidney disease progression. The TGF-β1/Smad signaling pathway, particularly Smad2 and Smad3 mediate pro-fibrotic responses, while Smad7 exerts inhibitory effects.

aimThe study aimed to evaluate the therapeutic potential of paraxanthine (Para), an active caffeine metabolite, and azilsartan (Azil), an angiotensin II receptor blocker, in attenuating gentamicin (GM)-induced renal fibrosis through targeting Smad pathway and miRNA-21/200b.

methodsSeventy male albino mice were randomized into seven groups (n = 10): Control, GM, SIS3 + GM, Para + GM, Azil + GM, Para + SIS3 + GM, and Azil + SIS3 + GM. GM (40 mg/kg, I.P.) was administered daily for 7 days. Subsequently, Para (20.5 mg/kg) and Azil (5 mg/kg) were given orally, while SIS3 (2 mg/kg, I.P.) was administered for 7 days. Serum and urine renal function markers were measured. Renal histopathology, protein expression of TGF-β1, CTGF, Smad3, Smad2 and Smad7, and gene expression of miRNA-21 and miRNA-200b were evaluated.

resultsGM caused significant (p < 0.001) nephrotoxicity with elevated BUN, serum creatinine, urinary albumin/creatinine ratio, and KIM-1 and increased fibrosis and marked type I collagen deposition compared to normal control. However, treatments with Para & Azil resulted in significant (p < 0.05) improvement in renal functions. Pro-fibrotic markers TGF-β1, connective tissue growth factor (CTGF), Type I Collagen, Smad 2 and Smad3 were reduced, while Smad7 was increased in treated groups versus GM group. Additionally, miRNA-21 was downregulated and miRNA-200b was upregulated following treatments.

conclusionParaxanthine and azilsartan demonstrated significantl restoring of kidney function and suppressing fibrotic progression. Their actions were mediated through regulation of Smad3/7 signaling and modulation of miRNA-21 and miRNA-200b expression, highlighting these pathways as promising therapeutic targets for the treatment of renal fibrosis.

Indexed as

BenzimidazolesKidneyKidney DiseasesMicroRNAsOxadiazolesSignal TransductionSmad3 ProteinTheophyllineTransforming Growth Factor beta1AnimalsFibrosisGene Expression RegulationGentamicinsMaleMiceSmad7 ProteinazilsartanBenzimidazolesGentamicinsMicroRNAsOxadiazolesSmad3 ProteinSmad3 protein, mouseSmad7 ProteinTheophyllineTransforming Growth Factor beta1AzilsartanGentamicinmiRNA-21/miRNA-200bParaxanthineRenal fibrosisTGF-β1/Smad signaling

Identifiers

PMID42116184
PMCPMC13182094

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.