Zulkhair Ali
Department Of Internal Medicine, Dr. Mohammad Hoesin Hospital, Palembang, Indonesia / Department Of Internal Medicine, Faculty Of Medicine, Universitas Sriwijaya, Palembang, Indonesia

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Dose-Dependent Amelioration of Ureteral Obstruction-Induced Kidney Fibrosis by Thymoquinone via GPx-Mediated Antioxidant Defense Chairil Makky; Suprapti; Muhammad Irsan Saleh; Zulkhair Ali; Novadian
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i5.1585

Abstract

Background: Chronic kidney disease inevitably progresses to renal fibrosis, driven heavily by oxidative stress and the depletion of endogenous antioxidants including Glutathione Peroxidase (GPx). Thymoquinone (TQ), a bioactive compound from Nigella sativa, exhibits potent antioxidant properties. This study investigates the dose-dependent efficacy of TQ in mitigating renal fibrosis via GPx modulation in a Unilateral Ureteral Obstruction (UUO) model. Methods: Thirty male Rattus norvegicus were randomly assigned to six groups (n=5): Sham, UUO + olive oil (Negative Control), UUO without oil, and UUO treated with TQ at 5, 10, and 20 mg/kg body weight for 14 days. Renal function (ureum, creatinine) and oxidative stress (Malondialdehyde) were measured. GPx mRNA expression was quantified using Reverse Transcription-Polymerase Chain Reaction. Tubulointerstitial injury (TII) and Positively Stained Area (PSA) for fibrosis were assessed histopathologically. Results: UUO induction significantly downregulated GPx expression (median 0.52 versus 1.40 in Sham, p=0.001) and exacerbated TII (score 3.58) and PSA (11.42%). TQ administration dose-dependently upregulated GPx expression, peaking at 20 mg/kg (median 0.62, p=0.009 versus Negative Control). Furthermore, TQ 20 mg/kg significantly reduced the TII score to 2.26 and decreased fibrotic PSA, ameliorating morphological damage. Conclusion: Thymoquinone exerts potent, dose-dependent antifibrotic and renoprotective effects in obstructive nephropathy by restoring GPx-mediated antioxidant defenses and preventing tubulointerstitial remodeling.
Adjuvant Resveratrol Reduces Albuminuria and Serum Transforming Growth Factor-β Without Improving Glomerular Filtration Rate in Diabetic Kidney Disease: A 12-Week Randomized Controlled Trial Eva Julita; Zulkhair Ali; Yulianto Kusnadi; Legiran
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 7 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i7.1627

Abstract

Background: Diabetic kidney disease (DKD) progresses through inflammation and fibrosis, with transforming growth factor-β (TGF-β) as the principal profibrotic mediator and albuminuria as a clinical surrogate of glomerular injury. Methods: We conducted a 12-week, double-blind, placebo-controlled randomized trial at Dr. Mohammad Hoesin General Hospital, Palembang, between October 2025 and January 2026 to evaluate adjuvant resveratrol on serum TGF-β, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR). Results: Of 61 randomized adults with DKD on standard care, 54 were analyzed (resveratrol n=27 received 25 mg twice daily, derived from Polygonum cuspidatum in 95% lecithin; placebo n=27). Within the resveratrol group, serum TGF-β fell from 123.7 to 77.1 pg/mL (p=0.008) and UACR from 94.1 to 89.8 mg/g (p=0.017); within placebo, UACR rose from 81.9 to 112 mg/g (p=0.029) while TGF-β change was non-significant (p=0.428). Between-group ΔUACR was significant (p<0.001), whereas ΔTGF-β (p=0.303) and ΔeGFR (p=0.567) were not. Multivariable linear regression identified resveratrol as an independent predictor of UACR reduction (B=−394.12 mg/g; 95% CI −659.53 to −128.71; p=0.004; adjusted R²=0.129). Baseline TGF-β was the dominant predictor of ΔTGF-β (B=−0.81; p<0.001; adjusted R²=0.701), and baseline LFG stage predicted ΔeGFR (B=−4.76; p=0.021). Mild bloating was reported in 14.8% of resveratrol versus 11.1% of placebo recipients; no serious adverse events occurred. Conclusion: Adjuvant low-dose resveratrol reduces albuminuria and serum TGF-β over 12 weeks in DKD without short-term improvement in eGFR, supporting an antifibrotic biomarker signal that warrants longer trials.
Co-Authors Abdul Hakim R Ade Yonata Ade Yonata, Ade Agustina H Akbar, Kgs. M. Yusuf Arief Akbar, M Yusuf Arief Ali Ghanie Alif Fathur Rachman, Muhammad Alwi Shahab Alwi Shahab Anggelia Puspasari Arief Akbar, Kgs M Yusuf Arif, Cut Wulan Chairil Makky Christin, Theresia Citra Maharani Deddy Primadona Mulia Devi, SNA Ratnasari Dila Siti Hamidah Eddy Mart Salim Edy Nur Rachman Effendi, Ian Elfiani Elfiani Elfiani Emilia Emilia Erial Bahar Erial Bahar Erial Bahar, Erial Erwin Sukandi Eva Julita Fadil Pramudhya Hoesain Fadil Pramudhya Husein Fadil Pramudya Fauzan Azhari, Fauzan Ferawaty, Ferawaty Ferry Usnizar Ferry Yusrizal Fitri Rahmariani Fitria Koeshardani Harun Hudari Huntari Harahap Ian Effendi Ian Effendi Ian Effendi Ika Kartika Ika Kartika Edi P Indrajaya, Taufik Irawan, Rico Irfannuddin Irfannuddin Istiqomah, Amelia Junaidi A Kartika, Herleni Kendenan, Margaretha Kgs M Yusuf Arief Akbar Kgs. M. Yusuf Arief Akbar kurniati, nova Kusrini, Ida Legiran Legiran Lidiawati Handayani Lilik Pranata M Yusuf Arief Akbar Mediarty Mediarty Syahrir Muhammad Irsan Saleh Muhammad Irsan Saleh Muhammad Yusri Mulia, Deddy Primadona Nova Kurniati Novadian Novadian Novadian Novadian, Novadian Novadian Suhaimi Novadian Suhaimi Novadian Suhaimi Novandra AP Nurul Ramadhani Umareta Nyimas Natasha Ayu Shafira R.M. Suryadi Tjekyan Radiyati Umi Partan Ramadhan, Philosophia Ratna Maila Dewi Anggraini Reinanda Marizki R Rery TF Yuniarti RM Suryadi Tjekyan Rostika Dewi Shahab, Alwi Slamet, Suprapti SNA Ratnasari Devi Suhaimi, Novadian Suprapti Suprapti Slamet Suprapti Suprapti Suprapti Suprapti Syahpri Putra Wangsa Taufik Indrajaya Taufik Indrajaya Trinovita Andraini Wangsa, Syahpri Putra Yudhie Tanta Yulianto kusnadi