Browsing by Author "Ural, Cemre"

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Citation - WoS: 6
Citation - Scopus: 5
Antioxidant Effect of Epigallocatechin-3 in a Bleomycin-Induced Scleroderma Model
(Turkish League Against Rheumatism, 2019) Kocak, Ayse; Harmancı, Duygu; Cavdar, Zahide; Ural, Cemre; Birlik, Merih; Sarioglu, Sulen; Yilmaz, Osman; Akdoğan, Gül
Objectives: This study aims to evaluate the antioxidant effects of epigallocatechin-3-gallate (EGCG) in a bleomycin (BLM)-induced scleroderma model. Materials and methods: Thirty-two healthy female Balb-c mice (6-8-week-old; weighing 22 +/- 5 g) were used in this study. The mice were randomly divided into four groups: control (n=8), BLM (n=8), BLM+EGCG (n=8), and EGCG (n=8). Skin tissue specimens were collected at the end of the experiments. Histopathological examinations of skin tissues were performed. Skin samples were assessed for total superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. The phosphorylation of p-38 mitogen-activated protein kinase and Akt protein (the serine-threonine protein kinase encoded by the AKT), as well as the nuclear factor-kappa B (NF-kappa B) levels, were analyzed by western blotting. Results: Epigallocatechin-3-gallate-treated groups were observed to have reduced connective tissue fibrosis in the dermis area using Masson's trichrome staining method. Pp-38 and NF-kappa B were found to decrease significantly in the BLM + EGCG group compared with the BLM group. Parallel to these findings, phosphorylated Akt protein was found to increase in the BLM + EGCG group compared with the BLM group. SOD activity was increased in the EGCG group and content of MDA level was decreased in EGCG groups. Conclusion: The results of the present study demonstrated that EGCG represses pp-38 and NF-kappa B signaling pathways, exerting a protective effect for scleroderma through its anti-oxidative role.
Citation - WoS: 2
Citation - Scopus: 2
Preventative Effect of Montelukast in Mild To Moderate Contrast-Induced Acute Kidney Injury in Rats Via Nadph Oxidase 4, P22phox and Nuclear Factor Kappa-B Expressions
(Springer, 2025) Simsek, Oguzhan; Baris, Elif; Ural, Cemre; Incir, Canet; Aydemir, Selma; Gumustekin, Mukaddes; Arici, Mualla Aylin
Reactive oxygen species (ROS) generation, inflammation and apoptosis are observed in contrast-induced acute kidney injury (CI-AKI). NOX4, isoform of NADPH oxidase main regulatory enzyme for ROS generation, is mostly expressed in the kidney and co-localized with p22phox. It is investigated the effect of antioxidant, anti-inflammatory and anti-apoptotic montelukast pre-treatment on expression of NOX4, p22phox and NF-kappa B in preventing CI-AKI in rats in this study. Wistar male rats randomized into four groups: 1. Control (C), 2. CI-AKI (iohexol; 3 g iodine/kg), 3. Montelukast (10 mg/kg) (M), 4. M + CI-AKI. Rats sacrificed on the 7th day. Urine and serum creatinine and serum Kidney injury molecule-1 (KIM-1) levels measured. NF-kappa B, NOX-4, p22phox mRNA and protein expressions, TNF-alpha, KIM-1 mRNA expressions, ROS and caspase-3 evaluated from kidney tissue. Histological injury scored. ANOVA and Kruskal-Wallis tests were used for analysis parametric and nonparametric data, respectively. p < 0.05 considered statistically significant. Tubular injury score, KIM-1 and caspase-3 levels increased in CI-AKI group compared to C group (p < 0.05). TNF-alpha, NF-kappa B, NOX-4, p22phox, KIM-1 mRNA expressions and ROS levels increased in CI-AKI group compared to C group (p < 0.001 and p < 0.05). NF-kappa B, NOX-4, p22phox protein expressions increased in CI-AKI group compared to C group (p < 0.05) and decreased in the M + CI-AKI group compared to CI-AKI group (p < 0.01, p < 0.05, p < 0.05). TNF-alpha, NF-kappa B, NOX-4, p22phox, KIM-1 mRNA expressions and ROS levels decreased with montelukast pre-treatment (p < 0.001). One of the mechanism of increased ROS level in the CI-AKI model is related the increase the expression of NOX4 and p22phox and montelukast pre-treatment has a protective effect by decreasing NOX4 and p22phox mRNA and protein expressions.
Citation - WoS: 11
Citation - Scopus: 12
Protective Effects of Alpha-Lipoic Acid on Bleomycin-Induced Skin Fibrosis Through the Repression of Nadph Oxidase 4 and Tgf-Beta 1/Smad3 Signaling Pathways
(Sage Publications Ltd, 2022) Kocak, Ayse; Ural, Cemre; Harmancı, Duygu; Oktan, Mehmet Asi; Afagh, Aysan; Sarioglu, Sulen; Yilmaz, Osman; Akdoğan, Gül
The aim of this study was to determine the protective effects of alpha-lipoic acid (ALA), which is known as a powerful antioxidant, and the possible related molecular mechanisms that mediate its favorable action on skin fibrosis in the bleomycin (BLM)-induced scleroderma (SSc) model in mice. The experimental design was established with four groups of eight mice: Control, ALA (100 mg/kg), BLM (5 mu g/kg), and BLM + ALA group. BLM was administered via subcutaneous (sc) once a day while ALA was injected intraperitoneally (ip) twice a week for 21 days. Histopathological and biochemical analyses showed that ALA significantly reduced BLM-induced dermal thickness, inflammation score, and mRNA expression of tumor necrosis factor-alpha (TNF-alpha) in the skin. Besides, the mRNA expressions of the subunits of NADPH oxidase, which are Nox4 and p22phox, were found to be significantly induced in the BLM group. However, ALA significantly reduced their mRNA expression, which were in parallel to its decreasing effect on serum total oxidant status (TOS) level. Moreover, it was found that ALA downregulated the mRNA expressions of alpha-smooth muscle actin (alpha-SMA), collagen type I and fibronectin in the skin tissue of the BLM group. Additionally, it was shown that ALA reduced significantly the TGF-beta 1 and p-Smad3 protein expressions in the BLM + ALA group. On the other hand, ALA did not exhibit any significant effect on the p38 mitogen-activated kinase (MAPK) activation induced by BLM. All these findings point out that ALA may be a promising treatment for the attenuation of skin fibrosis in SSc patients.
Citation - WoS: 1
Citation - Scopus: 2
Selective JAK-1 Inhibitor Upadacitinib and Peptide PD29 Modulate the JAK and TGF-β/Smad Signaling Pathways Reducing Experimental Dermal Fibrosis
(Pergamon-elsevier Science Ltd, 2025) Kocak, Ayse; Ural, Cemre; Cavdar, Zahide; Sarioglu, Sulen; Akdogan, Gul; Birlik, Merih
This study investigates the antifibrotic and anti-inflammatory effects of Janus kinase (JAK) inhibitors and the PD29 peptide in the context of systemic sclerosis (SSc), a condition characterized by dermal thickening, chronic inflammation, and excessive extracellular matrix deposition. Pulmonary arterial hypertension (PAH) and pulmonary fibrosis represent serious and often fatal complications associated with SSc. The pathogenesis of SSc involves dysregulation of immune responses and aberrant activation of signaling pathways, including TGF beta/Smad. The antifibrotic properties of upadacitinib, a selective JAK1 inhibitor, and PD29 peptide were evaluated using a bleomycin-induced SSc mouse model and primary human lung fibroblasts. Both agents, administered individually or in combination, significantly attenuated dermal thickening, myofibroblast transdifferentiation, collagen deposition, and activation of the TGF-beta 1 signaling axis. In vivo and in vitro analyses demonstrated that upadacitinib and PD29 downregulated key fibrotic markers, including alpha-SMA, JAK1, TGF-beta 1, Smad2, and collagen-1, at both the gene and protein levels. Furthermore, treatment significantly reduced systemic inflammatory cytokines, including IL-6 and TNF-alpha. Notably, combination therapy exhibited a more pronounced effect compared to monotherapy. These findings suggest that upadacitinib and PD29 exert potent antifibrotic and anti-inflammatory effects through suppression of TGF-beta 1-mediated Smad2/3 signaling, predominantly via inhibition of JAK1 activation. Consequently, JAK inhibitors and PD29 represent promising therapeutic candidates for the management of fibrosis in systemic sclerosis.