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Öğe Alpha-lipoic acid prevents doxorubicin-induced acute hepatorenal toxicity in rats by reducing oxidative and inflammatory stress to suppress autophagy(Oxford Univ Press, 2025) Yeni, Yesim; Cicek, Betul; Hacimuftuoglu, Ahmet; Ozkaraca, Mustafa; Mokhtare, BehzadDoxorubicin (DOX) is a commonly used medicine in cancer therapy. This drug accumulation in healthy tissues causes harmful clinical outcomes. Strategies that reduce oxidative damage, including alpha-lipoic acid (ALA) treatment, have been proposed to diminish toxic effects on healthy cells by raising the therapeutical effect of DOX on cancer cells. In this study, the preventive effects of ALA, against DOX-induced hepatorenal harm in rats were researched biochemically, molecularly, histopathological, and immunohistochemical. The experiment was designed for 10 days and 4 groups of 8 rats were created. ALA was administered orally to rats at a dosage of 200 mg/kg for 10 days and DOX was administered intraperitoneally at an only dosage of 30 mg/kg on day 8. To define oxidative stress, SOD, GSH, MPO, MDA, GPx, and CAT levels were evaluated. Hepatorenal harm was detected both histopathologically and by serum creatinine, ALT, ALP, AST, and urea analyses To detect the effect of inflammation, NF-kappa B, IL-1 beta, TNF-alpha levels, were defined in the liver, and AQP-2 and NPHS1 levels in the kidney. In addition, APG5L, Beclin 1, and LC3B expressions were determined immunohistochemically. It was determined that DOX-induced oxidative harm reduced and hepatorenal function markers improved in ALA-applied groups. It was also determined that ALA pretreatment had a regulative effect on NF-kappa B, AQP-2, TNF-alpha, NPHS1, and IL-1 beta levels and prevented the rise in DOX-induced LC3B, Beclin 1, and APG5L expression. Histopathological analysis showed that it prevented hepatorenal harm. As a result, ALA demonstrated its protective potential against DOX-induced hepatorenal toxicity.Öğe Ameliorating effect of S-Allyl cysteine (Black Garlic) on 6-OHDA mediated neurotoxicity in SH-SY5Y cell line(Elsevier Inc., 2024) Yeni, Yesim; Cicek, Betul; Yildirim, Serkan; Bolat, İsmail; Hacimuftuoglu, AhmetTherapeutic approaches based on isolated compounds derived from natural products are more common in preventing diseases involving inflammation and oxidative stress at present. S-allyl cysteine (SAC) is a promising garlic-derived organosulfur compound with many positive effects in cell models and living systems. SAC has biological activity in various fields, enclosing healing in learning and memory disorders, neurotrophic effects, and antioxidant activity. In this study, we purposed to identify the neuroprotective activity of SAC toward 6-OHDA-induced cell demise in the SH-SY5Ycell line. For this purpose, 6-OHDA-induced cytotoxicity, and biochemical, and gene expression changes were evaluated in SH-SY5Y cells. SH-SY5Y cells grown in cell culture were treated with SAC 24 h before and after 6-OHDA application. Then, cell viability, antioxidant parameters, and gene expressions were measured. Finally, immunofluorescence staining analysis was performed. Our results showed that SAC increased cell viability by 144 % at 80 µg/mL with pre-incubation (2 h). It was observed that antioxidant levels were significantly increased and oxidative stress marker levels were decreased in cells exposed to 6-OHDA after pre-treatment with SAC (p<0.05). SAC supplementation also suppressed the increase in pro-inflammation levels (TNF-α/IL1/IL8) caused by 6-OHDA (p < 0.05). While 8-OHdG and Nop10 expressions were observed at a mild level in SAC pretreatment depending on the dose, 8-OHdG, and Nop10 expressions were observed at a moderate level in SAC treatment after 6-OHDA application (p<0.05). Our findings demonstrate the positive effect of pretreatment with SAC on SH-SY5Y cells injured by 6-OHDA, suggesting that SAC may be beneficial for neuroprotection in regulating oxidative stress and neuronal survival in an in vitro model of Parkinson's disease. © 2024 The AuthorsÖğe Antiproliferative effects of cadmium sulfide nanoparticles obtained from walnut shells by green synthesis method on SH-SY5Y cell line(Elsevier Inc., 2024) Yeni, Yesim; Nadaroglu, Hayrunnisa; Ertugrul, M. Sait; Hacimuftuoglu, Ahmet; Alayli, AzizeNanoparticles are attracting attention for their potential therapeutic applications, particularly in cancer therapy, underscoring their importance in medicine. Cadmium sulfide nanoparticles, known for their robust catalytic and optical properties, are classified as chalcogenides and show promise for cancer diagnosis and treatment. Neuroblastoma, a common solid tumor in childhood, poses a significant health threat with different outcomes depending on its biological subtype. This study evaluated the antiproliferative effects of cadmium sulfide nanoparticles on the SY-SH5Y cell line. Walnut shell extract and Na2S were used to facilitate the synthesis of cadmium sulfide nanoparticles by green synthesis. Characterization of the synthesized cadmium sulfide nanoparticles was performed by Fourier transform infrared spectroscopy, scanning electron microscopy, and x-ray diffraction analyses. The SH-SY5Y cell line was cultured in a standard cell culture medium and then exposed to different cadmium sulfide nanoparticles (10–25–50–75–100 µg/mL) for 24 hours. Cell viability, oxidant, and antioxidant levels were then assessed using a 3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolyum bromür, total antioxidant, and total oxidant assays. The data showed that applying 100 μg/mL cadmium sulfide nanoparticles resulted in a significant decrease in cancer cell viability of up to 40.96 % (p<0.05). The cadmium sulfide nanoparticles had a dose-dependent effect on the SH-SY5Y cell line. Furthermore, cadmium sulfide nanoparticles increased oxidative activity in neuroblastoma cells, which was consistent with the results of the 3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolyum bromür assay. In conclusion, cadmium sulfide nanoparticles exhibited potent activity against the neuroblastoma cell. This study highlights the antiproliferative efficacy of green-synthesized cadmium sulfide nanoparticles with walnut shell extract on relevant cancer cell lines. © 2024 The AuthorsÖğe AuNPs with Cynara scolymus leaf extracts rescue arsenic-induced neurobehavioral deficits and hippocampal tissue toxicity in Balb/c mice through D1R and D2R activation(Elsevier, 2024) Cicek, Betul; Hacimuftuoglu, Ahmet; Yeni, Yesim; Kuzucu, Mehmet; Genc, Sidika; Cetin, Ahmet; Taghizadehghalehjoughi, AliThe present study was designed to evaluate whether AuNPs (gold nanoparticles) synthesized with the Cynara scolymus (CS) leaf exert protective and/or alleviative effects on arsenic (As)-induced hippocampal neurotoxicity in mice. Neurotoxicity in mice was developed by orally treating 10 mg/kg/day sodium arsenite (NaAsO2) for 21 days. 10 mu g/g AuNPs, 1.6 g/kg CS, and 10 mu g/g CS-AuNPs were administered orally simultaneously with 10 mg/ kg As. CS and CS-AuNPs treatments showed down-regulation of TNF-alpha and IL-1 beta levels. CS and CS-AuNPs also ameliorated apoptosis and reduced the alterations in the expression levels of D1 and D2 dopamine receptors induced by As. Simultaneous treatment with CS and CS-AuNPs improved As-induced learning, memory deficits, and motor coordination in mice assessed by water maze and locomotor tests, respectively. The results of this study provide evidence that CS-AuNPs demonstrated neuroprotective roles with antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as improving D1 and D2 signaling, and eventually reversed neurobehavioral impairments.Öğe Chlorogenic Acid Attenuates Doxorubicin-Induced Oxidative Stress and Markers of Apoptosis in Cardiomyocytes via Nrf2/HO-1 and Dityrosine Signaling(Mdpi, 2023) Cicek, Betul; Hacimuftuoglu, Ahmet; Yeni, Yesim; Danisman, Betul; Ozkaraca, Mustafa; Mokhtare, Behzad; Taghizadehghalehjoughi, Ali(1) Background: Doxorubicin (DOX) is extensively used for cancer treatments; however, its clinical application is limited because of its cardiotoxic adverse effects. A combination of DOX and agents with cardioprotective properties is an effective strategy to ameliorate DOX-related cardiotoxicity. Polyphenolic compounds are ideal for the investigation of novel cardioprotective agents. Chlorogenic acid (CGA), an essential dietary polyphenol found in plants, has been previously reported to exert antioxidant, cardioprotective, and antiapoptotic properties. The current research evaluated CGA's in vivo cardioprotective properties in DOX-induced cardiotoxicity and the probable mechanisms underlying this protection. (2) Methods: CGA's cardioprotective properties were investigated in rats that were treated with CGA (100 mg/kg, p.o.) for fourteen days. The experimental model of cardiotoxicity was induced with a single intraperitoneal (15 mg/kg i.p.) injection of DOX on the 10th day. (3) Results: Treatment with CGA significantly improved the DOX-caused altered cardiac damage markers (LDH, CK-MB, and cTn-T), and a marked improvement in cardiac histopathological features accompanied this. DOX downregulated the expression of Nrf2/HO-1 signaling pathways, and the CGA reversed this effect. Consistently, caspase-3, an apoptotic-related marker, and dityrosine expression were suppressed, while Nrf2 and HO-1 expressions were elevated in the cardiac tissues of DOX-treated rats after treatment with the CGA. Furthermore, the recovery was confirmed by the downregulation of 8-OHdG and dityrosine (DT) expressions in immunohistochemical findings. (4) Conclusions: CGA demonstrated a considerable cardioprotective effect against DOX-induced cardiotoxicity. One of the possible mechanisms for these protective properties was the upregulation of the Nrf2/HO-1-dependent pathway and the downregulation of DT, which may ameliorate oxidative stress and cardiomyocyte apoptosis. These findings suggest that CGA may be cardioprotective, particularly in patients receiving DOX-based chemotherapy.Öğe Effects of quercetin-immobilized albumin cerium oxide nanoparticles on glutamate toxicity: in vitro study(Springer, 2025) Yeni, Yesim; Genc, Sidika; Nadaroglu, Hayrunnisa; Hacimuftuoglu, AhmetOne aspect of glutamate (Glut) toxicity may be the opening of the blood-brain barrier to albumin (Al), which in itself can cause nerve cell death. Quercetin (Q) is a polyphenolic substance and has a neuroprotective effect. Cerium oxide nanoparticles (Ce(2)O(3)NPs) are highly interested in biological applications due to their antioxidant properties. The current study aimed to investigate the impact of Q-immobilized Al+Ce(2)O(3)NPs in Glut-induced neurotoxicity, mainly focusing on cell viability and neurobiochemical changes. Hydrothermal synthesis and characterization of Q-immobilized Al+Ce(2)O(3)NPs were performed. After preparing the primary neuron culture, it was exposed to Glut to induce neurotoxicity. Then, various doses of Ce2O3NP, Al+Ce2O3NP, and Q+Al+Ce(2)O(3)NPs (1, 5, 10, and 25 mu g/ml) were applied to the wells and incubated for 24 h. Then, cell viability was determined by MTT analysis. Additionally, oxidative stress parameters were measured. When the obtained data were examined, it was shown that cell viability decreased with Glut concentration but significantly increased with Q+Al+Ce(2)O(3)NPs treatment. When oxidative stress markers were considered, Glut treatment increased LDH, AChE, and TOS levels, while TAC and GSH levels decreased. However, the trend changed after Q+Al+Ce(2)O(3)NPs treatment, suggesting that damaged neurons were protected against oxidative stress. The results of this study indicate that Q+Al+Ce2O3NP can ameliorate Glut-induced neurotoxicity, especially when used at a dose of 25 mu g/ml.Öğe Exploring the anti-inflammatory activity of boron compounds through the miR-21/PTEN/AKT pathway in cecal ligation and puncture-induced sepsis(Spandidos Publ Ltd, 2025) Sevim, Cigdem; Ozkaraca, Mustafa; Kara, Mehtap; Taghizadehghalehjoughi, Ali; Genc, Sidika; Yeni, Yesim; Mendil, Ali SefaThe present study investigated the impact of boric acid (BA) and borax (BX) on markers of inflammation and modifications in miR-21/PTEN/AKT pathway genes in the liver and kidney tissues of Sprague Dawley male rats with sepsis induced by cecal ligation and puncture (CLP). A total of 60 male Sprague Dawley rats were randomly divided into 6 groups, each containing 10 animals as follows: Control, CLP (where the model was created), 20 mg/kg BX (CLP + BX1), 40 mg/kg BX (CLP + BX2), 20 mg/kg BA (CLP + BA1) and 40 mg/kg BA (CLP + BA2). Liver and kidney tissues were analyzed for histopathological changes, immunopositivity for tumor necrosis factor-alpha, interleukin (IL)-6 and IL-10, and gene expression of microRNA-21 (miR-21), phosphatase and tensin homolog (PTEN) and AKT. Gene expression analysis in the liver tissues revealed a significant decrease in miR-21, and a marked but not significant decrease in PTEN levels in the CLP group, while AKT expression was significantly increased in the CLP group, and was significantly decreased in CLP + BA1 group compared with in the CLP group. In the kidney tissues, miR-21 levels were significantly decreased in the CLP group, but the CLP + BA2 group showed a significant increase compared with in the CLP group. These results suggest the potential therapeutic benefits of low-dose BA and BX in ameliorating sepsis-induced tissue damage, emphasizing the need for further exploration of their mechanisms of action.Öğe Glioblastoma cell-derived exosomes induce cell death and oxidative stress in primary cultures of olfactory neurons. Role of redox stress(Springer, 2023) Yeni, Yesim; Taghizadehghalehjoughi, Ali; Genc, Sidika; Hacimuftuoglu, Ahmet; Yildirim, Serkan; Bolat, IsmailBackgroundGlioblastoma multiforme, described as glioblastoma, is a malignancy originating from glial progenitors in the central nervous system and is the most malignant subtype of brain tumors which attracted researcher's attention due to their high recurrence and mortality despite optimal treatments. In the study, we aimed to research whether glioblastoma-originated exosomes play a role in olfactory nerve cell toxicity.Methods and resultsFor this aim, exosomes obtained from U373 and T98G cells were applied to olfactory nerve cell culture at distinct doses. Then, glutathione (GSH), lactate dehydrogenase (LDH), total antioxidant capacity (TAC), 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT), total oxidant status (TOS) and Immunofluorescence analyzes were performed. We found that both glioblastoma-derived exosomes decreased cell viability in olfactory neurons with increasing doses. According to the obtained data, the olfactory neuron vitality rate was 71% in T98G-exosome, but the decrease in U373-exosome was more obvious (48%). In particular, the 100 mu g/ml dose exacerbated oxidative stress by increasing TOS. It also increased cellular apoptosis compared to the control group due to LDH leakage. However, the results of GSH and TAS showed that antioxidant levels were significantly reduced.ConclusionIn the microenvironment of olfactory neurons, GBM-derived exosomes increased oxidative stress-induced toxicity by reducing TAC and GSH levels. Therefore, glioblastoma cells by induction of exosome-based stress support malignant growth.Öğe In Vitro Effect of Boron Compounds in Combination with Photobiomodulation Therapy by 905 nm on the Viability of Human Gingival Fibroblasts(Kafkas Univ, Veteriner Fakultesi Dergisi, 2025) Turgut, Ferda; Yanmaz, Latif Emrah; Yildirim, Serkan; Taghizadehghalehjoughi, Ali; Yeni, Yesim; Okur, Sitkican; Orhun, Omer TarikThis study aimed to evaluate the effect of Low-level laser therapy (LLLT) and Boric acid (BA) or Borax decahydrate (BD) on the cell survival of gingival fibroblasts. Fibroblast planted plates were divided into 10 groups: Control group, BD 100 mu g/mL (BD 100), BD 200 mu g/mL (BD200), BA 100 mu g/mL (BA100), BA 200 mu g/mL (BA200), LLLT, LLLT+BD100 mu g/mL (LLLT+BD100), LLLT+BD200 mu g/mL (LLLT+BD200), LLLT+BA100 mu g/mL (LLLT+BA100) and LLLT+BA 200 mu g/mL (LLLT+BA200) groups. LLLT was performed at a dose of 4 J/cm2 for 160 sec. Following LLLT, MTT analysis was performed after the cells were kept in the incubator for 24 h. The LLLT+BA 200 group exhibited the highest cell density. In MTT analysis, significantly higher cell numbers were observed in the BA200, LLLT+BA100, and LLLT+BA200 groups compared to the control group (P<0.05). Then, the 3-(4,5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide assay and 8-hydroxy-2'-deoxyguanosine and Bcl-2 Associated X-Protein were analyzed. The 8-hydroxy-2'-deoxyguanosine and Bcl-2 Associated X-Protein levels were decreased in the LLLT+BA200 group compared to the control group (P<0.05). This study suggests that BA200, LLLT+BA100, and LLLT+BA200 increase the survival of fibroblast cells.Öğe Morinda citrifolia protective effects on paclitaxel-induced testis parenchyma toxicity: An experimental study(Pergamon-Elsevier Science Ltd, 2024) Genc, Sidika; Cicek, Betul; Yeni, Yesim; Kuzucu, Mehmet; Hacimuftuoglu, Ahmet; Bolat, Ismail; Taghizadehghalehjoughi, AliThe current study aimed to investigate the sensitivity of male testis parenchyma cells to chemotherapy agents and the protective effects and mechanisms of Morinda citrifolia (Noni) administration against structural and functional changes before and after chemotherapy (Paclitaxel (PTX)). For this purpose, rats were randomly assigned into four groups (Control = G1, PTX 5 mg/kg = G2; PTX + Noni 10 mg/kg = G3, PTX + Noni 20 mg/kg = G4). PTX was injected intraperitoneally for 4 consecutive weeks, at a dose of 5 mg/kg to all groups except the control group. Then noni was administrated in 10 (G3) and 20 (G4) mg/kg groups orally (gavage) for 14 days. Biochemical analyses, Real-Time Polymerase Chain Reaction (PCR), and immunohistochemical analyses were performed. According to our results, Total Oxidative Stress (TOS) and Malondialdehyde (MDA) were significantly increased in the PTX group (P < 0.01). Superoxide Dismutase (SOD) enzyme activity and Total Antioxidant Capacity (TAC) levels were decreased (P < 0.01). The changes in the rats treated with PTX + Noni 20 mg/ kg were noteworthy. The increased levels of IL1-beta (Interleukin 1 beta) and TNF alpha (tumor necrosis factor-alpha) with PTX were down-regulated after treatment with PTX + Noni 20 mg/kg (P < 0.01) (9 % and 5 % respectively). In addition, Noni restored the testicular histopathological structure by reducing caspase-3 expression and significantly (61 %) suppressed oxidative DNA damage and apoptosis (by regulating the Bax (bcl-2-like protein 4)/Bcl-2 (B-cell lymphoma gene-2) ratio). In conclusion, Noni reduced cellular apoptosis and drastically changed Caspase 8 and Bax/Bcl-2 levels. Furthermore, it considerably decreases oxidative damage and can be used in testicular degeneration.Öğe Neuroprotective effects of L-Dopa-modified zinc oxide nanoparticles on the rat model of 6-OHDA-ınduced Parkinson's disease(Nature Portfolio, 2024) Yeni, Yesim; Genc, Sidika; Ertugrul, Muhammed Sait; Nadaroglu, Hayrunnisa; Gezer, Arzu; Mendil, Ali Sefa; Hacimuftuoglu, AhmetParkinson's disease (PD) is a chronic neurodegenerative case. As the disease progresses, the response time to doses of levodopa (L-Dopa) becomes shorter and the effects of the drug are severely limited by some undesirable side effects such as the 'on-off' phenomenon. In several diseases, including Parkinson's, nanoparticles can deliver antioxidant compounds that reduce oxidative stress. This study evaluates and compares the neuroprotective effects of L-Dopa-modified zinc nanoparticles (ZnNPs) in the 6-hydroxydopamine (6-OHDA)-induced PD rat model. For this purpose, the synthesis of NPs was carried out. Scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectrophotometer were used for characterization. The rats were randomized into 9 experimental groups: control, lesion group (6-OHDA), 6-OHDA + 5 mg/kg L-Dopa, 6-OHDA + 10 mg/kg L-Dopa, 6-OHDA + 20 mg/kg L-Dopa, 6-OHDA + 20 mg/kg ZnNPs, 6-OHDA + 40 mg/kg ZnNPs, 6-OHDA + 30 mg/kg ZnNPs + L-Dopa, and 6-OHDA + 60 mg/kg ZnNPs + L-Dopa. Behavioral tests were performed on all groups 14 days after treatment. Phosphatase and tensin homolog, Excitatory amino acid transporter 1/2, and Glutamine synthetase gene analyses were performed on brain samples taken immediately after the tests. In addition, histological and immunohistochemical methods were used to determine the general structure and properties of the tissues. We obtained important findings that L-Dopa-modified ZnNPs increased the activity of glutamate transporters. Our experiment showed that glutamate increases neuronal cell vitality and improves behavioral performance. Therefore, L-Dopa-modified ZnNPs can be used to prevent neurotoxicity. According to what we found, results show that L-Dopa-modified ZnNPs will lend to the effective avoidance and therapy of PD.Öğe Panax Ginseng Protects Against Doxorubicin-Induced Testicular Injury in Male Rats by Modulating NF-κB/COX-2 and AR Pathways(Springer, 2025) Yeni, Yesim; Cicek, Betul; Hacimuftuoglu, Ahmet; Ozkaraca, Mustafa; Mokhtare, BehzadPanax ginseng (PG) is a medicinal plant used for many years to treat many diseases. The current study aimed to investigate the possible prophylactic and therapeutic effects of PG extract on doxorubicin (DOX)-induced testicular toxicity in rats. 32 adult male Sprague-Dawley rats (200-250 g) were used in the experiment. The experimental groups were designed as control (normal saline, intraperitoneal), DOX (18 mg/kg, intraperitoneal), PG (200 mg/kg, gavage), and PG + DOX (200 mg/kg, gavage). After treatment, serum levels of testosterone, interleukin-1 beta (IL-1 beta), glutathione (GSH), luteinizing hormone (LH), superoxide dismutase (SOD), lactate dehydrogenase (LDH), catalase (CAT), follicle stimulating hormone (FSH), tumor necrosis factor-alpha (TNF-alpha), and malondialdehyde (MDA) were measured. Then, gene expression, histopathological, and immunohistochemical analyses were performed on testicular tissues. Compared to DOX, treatment with PG + DOX showed a significant improvement in serum levels of FSH, testosterone, LH, TNF-alpha, IL-1 beta, MDA, SOD, LDH, GSH, and CAT. It was also observed that PG + DOX decreased nuclear factor-kappa B and cyclooxygenase-2 expression levels, increased androgen receptor expression, restored testicular histopathological structure, and significantly improved spermatogenesis. The results of the present study showed that PG may have an ameliorative effect against DOX-induced male reproductive toxicity, as DOX causes male reproductive toxicity. It can be concluded that PG is one of the effects that protect against DOX-induced testicular toxicity in rats by reducing lipid peroxidation and activating the antioxidant system. In light of this information, PG may be a useful agent to prevent the testicular toxicity observed in men receiving DOX treatment.Öğe Protective Effect of HMG-CoA Reductase Inhibitor Rosuvastatin on Doxorubicin-Induced Cognitive Impairment, Oxidative Stress and Neuroinflammation: Possible Role of CREB, ERK1/2, and BDNF(Springer, 2025) Yeni, Yesim; Cicek, Betul; Hacimuftuoglu, Ahmet; Ozkaraca, Mustafa; Lacin, Burak BatuhanDuring or after chemotherapy, cognitive impairments characterized by forgetfulness, difficulty concentrating, and depressive and anxiety-like symptoms are observed. There is limited research examining the effects of rosuvastatin (RVS), an HMG-CoA reductase inhibitor, in the context of neuroinflammation-related cognitive disruption. Here, we aimed to investigate the neuroprotective potential of RVS against doxorubicin (DOX)-induced cognitive impairments. Experimental groups were planned as control (normal saline, intraperitoneal), DOX (total cumulative dose 10 mg/kg, intraperitoneal), RVS (10 mg/kg, oral, 20 days), and RVS + DOX. Efficacy was monitored by applying a battery of behavioral assessments, as well as biochemical, genetic, histopathological, and immunohistochemical examinations. Results from Morris water maze (MWM), passive avoidance, locomotion activity, and elevated plus maze (EPM) tests showed that DOX administration caused behavioral disorders. Moreover, DOX increased the levels of inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-alpha), while decreasing the levels of interleukin-10 (IL-10), glutathione (GSH), superoxide dismutase, catalase (SOD), endothelial nitric oxide (eNOS), and catalase (CAT). Co-treatment with RSV significantly attenuated DOX-induced behavioral changes and oxidative stress markers. In addition, similar to the immunohistochemical results, we determined that it increased the expression levels of extracellular signal-related kinases 1/2 (ERK1/2), cyclic adenosine monophosphate response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) and restored the histopathological structure of the brain. Therefore, these results indicated that RSV has a neuroprotective effect against DOX-induced cognitive impairment by reducing neurobehavioral impairments, exerting antioxidant and anti-inflammatory effects, and modulating brain growth factors.Graphical AbstractRSV ameliorated DOX-induced cognitive impairments by assessing oxidative stress, BDNF, CREB, and ERK1/2 expression. These beneficial effects induced by RSV provided strong protection against both cognitive dysfunction and anxiety-like behavior. RSV may help prevent or alleviate cognitive dysfunction in patients with various types of cancer undergoing chemotherapy and may have potential benefit in neurodegenerative diseasesÖğe Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries(Mdpi, 2023) Cicek, Betul; Hacimuftuoglu, Ahmet; Kuzucu, Mehmet; Cetin, Ahmet; Yeni, Yesim; Genc, Sidika; Taghizadehghalehjoughi, AliAccording to population-based studies, lung cancer is the prominent reason for cancer-related mortality worldwide in males and is also rising in females at an alarming rate. Sorafenib (SOR), which is approved for the treatment of hepatocellular carcinoma and renal cell carcinoma, is a multitargeted protein kinase inhibitor. Additionally, SOR is the subject of interest for preclinical and clinical trials in lung cancer. This study was designed to assess in vivo the possible effects of sorafenib (SOR) in diethylnitrosamine (DEN)-induced lung carcinogenesis and examine its probable mechanisms of action. A total of 30 adult male rats were divided into three groups (1) control, (2) DEN, and (3) DEN + SOR. The chemical induction of lung carcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg once a week for two weeks. The DEN-administered rats were co-treated with SOR of 10 mg/kg by oral gavage for 42 alternate days. Serum and lung tissue samples were analyzed to determine SRY-box transcription factor 2 (SOX-2) levels. The tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) levels were measured in lung tissue supernatants. Lung sections were analyzed for cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) histopathologically. In addition, cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) were analyzed by immunohistochemistry and immunofluorescence methods, respectively. SOR reduced the level of SOX-2 that maintenance of cancer stemness and tumorigenicity, and TNF-alpha and IL-1 beta levels. Histopathological analysis demonstrated widespread inflammatory cell infiltration, disorganized alveolar structure, hyperemia in the vessels, and thickened alveolar walls in DEN-induced rats. The damage was markedly reduced upon SOR treatment. Further, immunohistochemical and immunofluorescence analysis also revealed increased expression of COX-2 and JNK expression in DEN-intoxicated rats. However, SOR treatment alleviated the expression of these inflammatory markers in DEN-induced lung carcinogenesis. These findings suggested that SOR inhibits DEN-induced lung precancerous lesions through decreased inflammation with concomitant in reduced SOX-2 levels, which enables the maintenance of cancer stem cell properties.Öğe The Impact of Different Part Extracts of Peganum harmala L. on Human Colorectal Adenocarcinoma Cell Line (Caco-2)(Wiley, 2024) Tasci, Seymanur Yilmaz; Genc, Sidika; Yeni, Yesim; Karakaya, Songul[Abstract Not Available]Öğe The Impact of Various Extracts of Angelica purpurascens (Ave-Lall.) Gilli on Caco-2 Cell Line(Wiley, 2024) Tasci, Seymanur Yilmaz; Genc, Sidika; Yeni, Yesim; Karakaya, Songul[Abstract Not Available]
