Browsing by Author "Erol, Huseyin Serkan"

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Citation - WoS: 19
Citation - Scopus: 17
Effects of tocilizumab and dexamethasone on the downregulation of proinflammatory cytokines and upregulation of antioxidants in the lungs in oleic acid-induced ARDS
(BMC, 2022) Terzi, Funda; Alhılal, Mohammad; Demirci, Beste; Çınar, İrfan; Alhilal, Mohammad; Erol, Huseyin Serkan; 09.01. Department of Nursing / Hemşirelik Bölümü; 9. Faculty of Health Sciences / Sağlık Bilimleri Fakültesi; 01. Mardin Artuklu University / Mardin Artuklu Üniversitesi
Abstract Background: Acute respiratory distress syndrome (ARDS) is a life-threatening disease caused by the induction of infammatory cytokines and chemokines in the lungs. There is a dearth of drug applications that can be used to prevent cytokine storms in ARDS treatment. This study was designed to investigate the efects of tocilizumab and dexamethasone on oxidative stress, antioxidant parameters, and cytokine storms in acute lung injury caused by oleic acid in rats. Methods: Adult male rats were divided into fve groups: the CN (healthy rats, n=6), OA (oleic acid administration, n=6), OA+TCZ-2 (oleic acid and tocilizumab at 2 mg/kg, n=6), OA+TCZ-4 (oleic acid and tocilizumab at 4 mg/kg, n=6), and OA+DEX-10 (oleic acid and dexamethasone at 10 mg/kg, n=6) groups. All animals were euthanized after treatment for histopathological, immunohistochemical, biochemical, PCR, and SEM analyses. Results: Expressions of TNF-α, IL-1β, IL-6, and IL-8 cytokines in rats with acute lung injury induced by oleic acid were downregulated in the TCZ and DEX groups compared to the OA group (P<0.05). The MDA level in lung tissues was statistically lower in the OA+TCZ-4 group compared to the OA group. It was further determined that SOD, GSH, and CAT levels were decreased in the OA group and increased in the TCZ and DEX groups (P<0.05). Histopathological fndings such as thickening of the alveoli, hyperemia, and peribronchial cell infltration were found to be similar when lung tissues of the TCZ and DEX groups were compared to the control group. With SEM imaging of the lung tissues, it was found that the alveolar lining layer had become indistinct in the OA, OA+TCZ-2, and OA+TCZ-4 groups. Conclusions: In this model of acute lung injury caused by oleic acid, tocilizumab and dexamethasone were efective in preventing cytokine storms by downregulating the expression of proinfammatory cytokines including TNF-α, IL-1β, IL-6, and IL-8. Against the downregulation of antioxidant parameters such as SOD and GSH in the lung tissues caused by oleic acid, tocilizumab and dexamethasone upregulated them and showed protective efects against cell damage.
Medicinal Evaluation and Molecular Docking Study of Osajin as an Anti-Inflammatory, Antioxidant, and Antiapoptotic Agent Against Sepsis-Associated Acute Kidney Injury in Rats
(Taylor & Francis Ltd, 2024) Alhilal, Mohammad; Erol, Huseyin Serkan; Yildirim, Serkan; Cakir, Ahmet; Koc, Murat; Alhilal, Suzan; Halici, Mesut Bunyami
Despite efforts to find effective drugs for sepsis-associated acute kidney injury (SA-AKI), mortality rates in patients with SA-AKI have not decreased. Our study evaluated the protective effects of isoflavone osajin (OSJ) on SA-AKI in rats by targeting inflammation, oxidative stress, and apoptosis, which represent the cornerstones in the pathophysiological mechanism of SA-AKI. Polymicrobial sepsis was induced in rats via the cecal ligation and puncture (CLP) technique. Markers of oxidative stress were evaluated in kidney tissues using biochemical methods. The expression of interleukin-33 (IL-33), 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, and kidney injury molecule-1 (KIM-1) was evaluated as indicators of inflammation, DNA damage, apoptosis, and SA-AKI respectively in the kidney tissues using immunohistochemical and immunofluorescent detection methods. The CLP technique significantly (p < 0.001) increased lipid peroxidation (LPO) levels and significantly (p < 0.001) decreased the activities of superoxide dismutase and catalase in kidney tissues. In the renal tissues, strong expression of IL-33, 8-OHdG, caspase-3, and KIM-1 was observed with severe degeneration and necrosis in the tubular epithelium and intense interstitial nephritis. In contrast, the administration of OSJ significantly (p < 0.001) reduced the level of LPO, markedly improved biomarkers of antioxidant status, decreased the levels of serum creatinine and urea, lowered the expression of IL-33, 8-OHdG, caspase-3, and KIM-1 and alleviated changes in renal histopathology. A promising binding score was found via a molecular docking investigation of the OSJ-binding mode with mouse IL-33 (PDB Code: 5VI4). Therefore, OSJ protects against SA-AKI by suppressing the IL-33/LPO/8-OHdG/caspase-3 pathway and improving the antioxidant system.
Osajin is a Promising Candidate for Sepsis-Induced Brain Damage via Suppression of the 8-OHdG/Bax/Caspase-3 Pathway in a Rat Model of Sepsis
(2025) Erol, Huseyin Serkan; Halıcı, Mesut; Koç, Murat; Alhılal, Mohammad; Yildirim, Serkan; Kiliçlioğlu, Metin; Alhilal, Suzan
Amaçlar: Doğal ürün olan osajinin, sepsis kaynaklı beyin hasarına karşı koruyucu etkisini, sepsisli sıçanların beyin dokusundaki 8-hidroksideoksiguanozin (8-OHdG)/Bcl-2 ile ilişkili × protein (Bax)/kaspaz-3 yolunu hedef alarak inceledik. Metotlar: Osajin, Maclura pomifera'nın meyvesinden izole edilip yapısı doğrulandı. Çekal ligasyon-punksiyon (CLP) yöntemi ile sıçanlarda beyin hasarı modeli oluşturuldu. Osajin, sepsise bağlı beyin hasarı olan hayvanlara 150 ve 300 mg/kg dozlarda uygulanmıştır. Ötenazi sonrasında histopatolojik inceleme, immünohistokimya ile 8-OHdG'nin tespiti ve immünfloresan teknik kullanılarak Bax ve kaspaz-3 ekspresyonunun tahmini beyin dokusunda yapıldı. Bulgular: Histopatolojik incelemede sepsisli sıçanların beyinlerinde şiddetli düzeyde inflamasyon, belirgin dejenerasyon ve nekroz görüldü. İmmünohistokimyasal ve immünfloresan analizlerin bulguları, CLP tekniğinin, sağlıklı sıçanlarla karşılaştırıldığında sepsisli sıçanların beyin dokularında belirgin 8-OHdG, Bax ve kaspaz-3 ekspresyonunu indüklediğini ortaya çıkardı. 150 mg/kg (p < 0.05) ve 300 mg/kg (p = 0.0022) dozlarda osajin'in uygulanması, histopatolojik değişiklikleri tersine çevirdiği ve sepsisli sıçanlarla kıyaslandığında artan 8-OHdG, Bax ve kaspaz-3 ekspresyonunu önemli ölçüde iyileştirdiği gözlendi. Sonuç: Histopatolojik, immünohistokimyasal ve immünfloresan kanıtlar, osajin'in, 8-OHdG/Bax/kaspaz-3 yolunu inhibe ederek sepsisin neden olduğu beyin hasarını tersine çevirebileceğini göstermektedir. Buna göre bu doğal ürünün, sepsisli hastalardaki beyin hasarının tedavisi için umut verici bir aday olabileceği gösterilmiştir.