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Öğe Investigation of cardioprotective effect of lercanidipine on doxorubicin-induced cardiotoxicity(Springer, 2023) Karakuyu, Nasif Fatih; Savran, Mehtap; Candan, Ibrahim Aydin; Buyukbayram, Halil Ibrahim; Erzurumlu, YalcinAlthough doxorubicin (DOX) is an effective anti-neoplastic drug for many types of cancer, particularly dose-related cardiotoxicity limits the use of the drug. In this study, it was aimed to investigate the protective effect of lercanidipine (LRD) against DOX-induced cardiotoxicity. In our study, 40 Wistar albino female rats were randomly divided into 5 groups as control, DOX, LRD 0.5 (DOX + 0.5 mg/kg LRD), LRD 1 (DOX + 1 mg/kg LRD), and LRD 2 (DOX + 2 mg/kg LRD). At the end of the experiment, the rats were sacrificed, and their blood, heart, and endothelial tissues were examined biochemically, histopathologically, immunohistochemically, and genetically. According to our findings, necrosis, tumor necrosis factor alpha activity, vascular endothelial growth factor activity, and oxidative stress were increased in the heart tissues of the DOX group. In addition, DOX treatment caused the deteriorations in biochemical parameters, and levels of autophagy-related proteins, Atg5, Beclin1, and LC3-I/II were detected. Significant dose-related improvements in these findings were observed with LRD treatment. Besides, Atg5, LC3-I/II, and Beclin1 levels evaluated by western blot revealed that LRD exerts a tissue protective effect by regulating autophagy in endothelial tissue. LRD treatment, which is a new-generation calcium channel blocker, showed antioxidant, anti-inflammatory, and anti-apoptotic properties in heart and endothelial tissue in a dose-dependent manner and also showed protective activity by regulating autophagy in endothelial tissue. With studies evaluating these mechanisms in more detail, the protective effects of LRD will be revealed more clearly.Öğe Investigation of the efficiency of pulsed electromagnetic field treatment and stretching exercise in experimental skeletal muscle injury model(Bmc, 2025) Ergan, Mesut; Keskin, Tahir; Candan, Ibrahim Aydin; Erzurumlu, Yalcin; Asci, Halil; Comlekci, Selcuk; Baskurt, FerdiObjective Pulsed electromagnetic fields (PEMF) and stretching exercises are safe and noninvasive methods that could have a therapeutic effect on tissue healing. This study aimed to assess the effectiveness of these methods in treatment of muscle injury (INJ). Method Rats were divided into 5 groups (Control, INJ, INJ + Exercise, INJ + PEMF, INJ + Exercise + PEMF). At the end of the experiment, genetic, histopathological, and immunohistochemical evaluations were made in the muscle tissue. Results Mononuclear cell infiltration, muscle degeneration, atrophy, and necrosis were found to be higher in the INJ group than in all groups (p < 0.001). On the 7th day, fibroblast growth factor (FGF) was found to be higher in the INJ group compared to both the control and the INJ + Exercise group (p < 0.05). On the 14th day, Vascular endothelial growth factor values were found to be higher in the injury group than the other groups except for the PEMF group (p < 0.05), and FGF values were higher in the injury group compared to all groups (p < 0.001). The expressions of transforming growth factor beta 1 (TGF-beta 1) and endothelial nitric oxide synthase (eNOS) on the 7th and 14th days showed a significant increase in the INJ group compared to the other groups (p < 0.001). Conclusion In this study, it has been shown that PEMF and stretching exercise is effective in the treatment of muscle injuries as they balance the inflammatory process in the muscle, have a positive effect on muscle development, accelerate healing, prevent fibrosis development by reducing TGF-beta 1 signaling, and inhibit inflammatory-induced eNOS activity.Öğe Melatonin receptor agonist ramelteon alleviates experimental acute ocular inflammation via HIF-1?/VEGF/E-NOS signaling(Sage Publications Ltd, 2023) Sofu, Gulsah Usta; Erzurumlu, Yalcin; Karaca, Umut; Candan, Ibrahim Aydin; Savran, Mehtap; Asci, Halil; Hasseyid, NurselPurpose: Ramelteon (RML) is a potent, selective agonist of the high-affinity melatonin receptor 1 and 2 receptors. In addition, RML is known to have antioxidant and anti-inflammatory effects. In this study, we aimed to investigate the effects of RML on HIF-1 alpha, VEGF and e-NOS signaling pathway in a rat model of endotoxin-induced uveitis (EIU). Methods: Twenty-eight Wistar albino rats were divided into 4 groups as controls, lypopolysaccharide (LPS) group (5 mg/kg i.p.), LPS + RML group (5 mg/kg i.p and 8 mg/kg orally, respectively) and RML group (8 mg/kg orally). EIU was induced by a single intraperitoneal LPS injection. Histopathological and genetical analyses were performed. Results: In histopathological analysis, LPS caused mild anterior uveitis characterized by increased surface area of iris leaflets and ciliary body due to edema, mild to moderate congestion, and inflammatory infiltrate 6 h following the injection. The pathological findings were reduced by RML. Higher inflammation levels seen in LPS group were significantly reduced in LPS + RML group. Also, HIF-1 alpha, eNOS and VEGF expressions increased in LPS and decreased in LPS + RML group. Conclusion: RML treatment reversed the changes in the HIF-1 alpha /eNOS/ VEGF signaling pathway in LPS-induced uveitis in rats, preventing the progression of the damage and showed positive effects.Öğe Novel regulation mechanism of adrenal cortisol and DHEA biosynthesis via the endogen ERAD inhibitor small VCP-interacting protein(Nature Research, 2022) İLhan, Recep; Üner, Göklem; Yilmaz, Sinem; Atalay-Sahar, Esra; Cayli, Sevil; Erzurumlu, Yalcin; Gözen, O?uzEndoplasmic reticulum-associated degradation (ERAD) is a well-characterized mechanism of protein quality control by removal of misfolded or unfolded proteins. The tight regulation of ERAD is critical for protein homeostasis as well as lipid metabolism. Although the mechanism is complex, all ERAD branches converge on p97/VCP, a key protein in the retrotranslocation step. The multifunctionality of p97/VCP relies on its multiple binding partners, one of which is the endogenous ERAD inhibitor, SVIP (small VCP-interacting protein). As SVIP is a promising target for the regulation of ERAD, we aimed to assess its novel physiological roles. We revealed that SVIP is highly expressed in the rat adrenal gland, especially in the cortex region, at a consistently high level during postnatal development, unlike the gradual increase in expression seen in developing nerves. Steroidogenic stimulators caused a decrease in SVIP mRNA expression and increase in SVIP protein degradation in human adrenocortical H295R cells. Interestingly, silencing of SVIP diminished cortisol secretion along with downregulation of steroidogenic enzymes and proteins involved in cholesterol uptake and cholesterol biosynthesis. A certain degree of SVIP overexpression mainly increased the biosynthesis of cortisol as well as DHEA by enhancing the expression of key steroidogenic proteins, whereas exaggerated overexpression led to apoptosis, phosphorylation of eIF2?, and diminished adrenal steroid hormone biosynthesis. In conclusion, SVIP is a novel regulator of adrenal cortisol and DHEA biosynthesis, suggesting that alterations in SVIP expression levels may be involved in the deregulation of steroidogenic stimulator signaling and abnormal adrenal hormone secretion. © 2022, The Author(s).
