Browsing by Author "Cavdar, Zahide"

Now showing 1 - 4 of 4

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: 4
Effects of Epigallocatechin-3 (egcg) on a Scleroderma Model of Fibrosis
(Walter De Gruyter Gmbh, 2018) Kocak, Ayse; Harmancı, Duygu; Birlik, Merih; Sarioglu, Sulen; Yilmaz, Osman; Cavdar, Zahide; Akdoğan, Gül
Objective: The aim of the present study was to evaluate the potential protective effects of epigallocatechin-3-gallate (EGCG) on fibrosis in bleomycin induced scleroderma model. Materials and methods: Thirty-two healthy female Balb-c mice with the average body weight of 22 +/- 5 g were used in this study. The mice were randomly divided into four groups as control (n=8), Bleomycin (n=8), Bleomycin+ EGCG (n =8) and EGCG (n =8). Skin tissue samples were collected to quantify matrix metalloproteinases (MMP-1, MMP-8, MMP-13), p-SMAD 2/3 and SMAD 2/3 in protein homogenates by western blotting. TGF-beta 1 expression was determined by real-time PCR. Immunohistopathological and histopathological examinations of skin tissues were also done. Results: When measured with Masson Trichrome, EGCG treatment was found to decrease fibrosis in connective tissue compared to the BLM injected control. EGCG was decreased dermal fibrosis. Bleomycin + EGCG group showed a significant reduction in fibrosis at the dermal surface area using hematoxylin measurements compared with the BLM group. MMP-1, MMP-8 protein levels were increased and p-SMAD 2/3 protein level was decreased. TGF-beta mRNA expression was decreased in the EGCG + BLM group compared with the BLM group. Conclusion: These results suggest an antifibrotic role for EGCG.
Ionizing Radiation-Induced Testicular Oxidative Stress and Apoptosis: The Role of Small GTPase RhoA
(Taylor & Francis Ltd, 2025) Manisaligil, Yasar Aysun; Yurt, Aysegul; Ozkan, Cemre Ural; Micili, Serap Cilaker; Sisman, Gizem; Cavdar, Zahide; Gumustekin, Mukaddes
PurposeThe effects of ionizing radiation on living organisms are mainly known as the generation of reactive oxygen species (ROS), apoptosis, and DNA damage. Small GTPases (RhoA, Rac1, Cdc42) are known to have roles in the regulation of oxidative stress and apoptosis. The aim of this study was to investigate the role of the RhoA molecule in testicular tissue damage due to oxidative stress and apoptosis induced by ionizing radiation.Material and methodIn this study, testicular tissues and blood samples obtained from our previous study were examined. In that study, rats were exposed to ionizing radiation at three different doses (0.02 Gy, 0.1 Gy, 5 Gy). Then tissue and blood samples were taken at three different times (2 hours, 24 hours, and 7 days) after irradiation. Immunohistochemical staining was performed to evaluate RhoA and cleaved caspase-3 expressions, while RhoA activity was assessed by G-LISA assay in testicular tissues. Serum malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were analyzed to evaluate oxidative stress.ResultsThe expression and activation of RhoA demonstrated a time-dependent increase across all levels of radiation doses. Similarly, the expression of cleaved caspase-3 also exhibited a time-dependent increase, consistent with the effects of radiation-induced damage observed in all experimental groups. After exposure to radiation, serum levels of MDA increased, while the activity of SOD decreased.ConclusionOur findings suggest that RhoA may contribute to radiation-induced testicular tissue damage by increasing oxidative stress and apoptosis.
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.