Medical Journal of the Islamic Republic Of Iran

en Potential Renoprotective Effect of Pirfenidone And Silymarin in Acute Kidney Injury Through Targeting miRNA 21 Pharmacology Pharmacology Original Research Original Research     Background: Pirfenidone (PFD) and silymarin (SIL) have demonstrated diverse pharmacological activities and investigated for their renoprotective potential in acute kidney injury (AKI). Their mechanisms involve antioxidant, anti inflammatory, and microRNA mediated pathways. This study evaluated their efficacy against folic acid induced AKI, with emphasis on modulation of miRNA 21.    Methods: 24 adult male albino rats were selected and distributed into four groups . Group 1 (Control): 6 rats received NaHCO3. To induce AKI in the remaining rats, a single dose of folic acid was administered intraperitoneally (250 mg/Kg). Rats were randomly distributed among groups consisting of: Group 2 (50 mg of folic acid was administered intraperitoneally); Group 3 (Administered folic acid and orally treated with pirfenidone at a dosage of 500 mg/kg/day); Group 4 (Administered folic acid and orally treated with silymarin 200 mg/kg/day). Both drugs were administered for three days prior to AKI induction and continued for four days thereafter, the all rats were sacrificed, blood samples were drawn, and renal tissues were harvested for renal function, oxidative stress markers, cytokines (TNF α, TGF β, IL 10), and miRNA 21 expression assessment. Histopathological changes were evaluated by H&E and PAS staining.    Results: Folic acid significantly elevated serum creatinine (2.68±0.10 vs. 0.70±0.06 in controls), urea (83.06±2.97 vs. 30.51±3.55), MDA (3.78±0.19 vs. 1.02±0.07), TNFα (137.36±4.98 vs. 42.15±3.12), and miRNA‑21 (2.64±0.13 vs. 1.01±0.05; P<0.050), while reducing SOD (0.64±0.05 vs. 1.92±0.08) and IL‑10 (4.39±0.29 vs. 19.87±1.42). Pirfenidone improved renal function (creatinine 1.76±0.04, urea 64.77±1.56), oxidative stress (MDA 2.30±0.04, SOD 1.56±0.09), and cytokines (TNFα 82.28±2.78, IL‑10 18.19±1.49). Silymarin produced significantly greater recovery than pirfenidone, with lower creatinine (1.47±0.05 vs. 1.76±0.04; P≤0.050), lower urea (56.89±5.05 vs. 64.77±1.56; P≤0.050), lower MDA (2.07±0.09 vs. 2.30±0.04; P≤0.050), lower TNFα (72.02±3.44 vs. 82.28±2.78; P≤0.050), and reduced miRNA‑21 (1.83±0.05 vs. 2.12±0.07; P≤0.050), alongside higher SOD (1.79±0.06 vs. 1.56±0.09; P≤0.050) and IL‑10 (21.8±1.54 vs. 18.19±1.49; P≤0.050). Histology confirmed near normal architecture in silymarin treated rats compared to partial recovery with pirfenidone.    Conclusion: Both pirfenidone and silymarin attenuate folic acid-induced acute kidney injury (AKI) through antioxidant, anti inflammatory, and miRNA 21 modulating effects. Silymarin demonstrated more protective effect. These findings support silymarin as a promising candidate for nephroprotection and warrant further mechanistic investigation.   Folic acid, AKI, Pirfenidone, Silymarin, MDA, SOD, TNFα, PAS, miRNA 21 611 623 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-9725-1&slc_lang=en&sid=1 Noha Samir Abdel Latif noha.gomaa@kasralainy.edu.eg 200319475328460098787 200319475328460098787 No Department of Medical Pharmacology, Faculty of Medicine, Cairo University, El Manial, Cairo 11562, Egypt Tayee E.M dr_sayed_1978@yahoo.com 200319475328460098788 0009-0002-3755-4456 No Department of Medical Pharmacology, Faculty of Medicine, Capital University (formerly Helwan University), Helwan, Cairo 4034572, Egypt Alsayed A. Abdelhady Alsayed.Abdelrahman@med.helwan.edu.eg 200319475328460098789 200319475328460098789 No Department of Human Anatomy and Evolutionary Biology, Faculty of Medicine, Capital University (formerly Helwan University), Helwan, Cairo 4034572, Egypt Manal H. Albadawi manal.albadawi@med.helwan.edu.eg 200319475328460098790 200319475328460098790 No Department of Human Anatomy and Evolutionary Biology, Faculty of Medicine, Capital University (formerly Helwan University), Helwan, Cairo 4034572, Egypt Abeer Abdelkader abeer.abdelkader@kasralainy.edu.eg 200319475328460098791 200319475328460098791 No Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, El Manial, Cairo 11562, Egypt Mostafa Ezz El-Din mustafa.elsayed@med.capu.edu.eg 200319475328460098792 0009-0009-4117-1811 Yes Department of Medical Pharmacology, Faculty of Medicine, Capital University (formerly Helwan University), Helwan, Cairo 4034572, Egypt Ahmed Mohammed Taha ahmed.taha@med.capu.edu.eg 200319475328460098793 0009-0003-9467-649X No Department of Medical Pharmacology, Faculty of Medicine, Capital University (formerly Helwan University), Helwan, Cairo 4034572, Egypt