Browsing by Author "Yakut, Seda"
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Article 18β-Glycyrrhetinic Acid-Loaded Silver Nanoparticles Mitigate Neuroinflammation and Endoplasmic Reticulum Stress in the Brain Tissue of Diabetic Rats(Mashhad University of Medical Sciences, 2026) Parlak, Secil Nazife; Yakut, Seda; Kara, Adem; Demir, Ozlem; Sebin, Saime OzbekObjective(s): Diabetes mellitus (DM) causes oxidative stress, neuroinflammation, and endoplasmic reticulum (ER) dysfunction that contribute to neurodegeneration. This study investigated the effects of 18 beta-glycyrrhetinic acid-loaded silver nanoparticles (18 beta-GA-AgNPs) on brain injury in diabetic rats. Materials and Methods: Fifty-six male Wistar rats were divided into eight groups: Sham, 18 beta-GA, AgNPs, 18 beta-GA-AgNPs, DM, DM+18 beta-GA, DM+AgNPs, and DM+18 beta-GA-AgNPs. Diabetes was induced by alloxan (120 mg/kg, IP), and treatments were administered orally for 14 days. Biochemical markers (MDA, GSH, SOD), histopathology, and expression of ER stress and apoptotic proteins (ATF6, IRE1, Caspase-3, BCL-2, CREB, TNF-alpha, and IL-1 beta) were evaluated. Results: The DM group exhibited significant increases in MDA, TNF-alpha, IL-1 beta, ATF6, and Caspase-3 with reduced GSH, SOD, and BCL-2, indicating oxidative stress, inflammation, apoptosis, and ER stress. In contrast, IRE1 levels remained unchanged in DM rats but showed a slight elevation in the AgNPs group. Treatment with 18 beta-GA-AgNPs markedly reduced MDA, TNF-alpha, IL-1 beta, ATF6, and Caspase-3, while restoring GSH, SOD, BCL-2, and CREB expression. Histopathological analysis confirmed neuronal apoptosis and perivascular and extracellular space enlargement in DM rats, whereas 18 beta-GA-AgNPs substantially attenuated these changes. Overall, 18 beta-GA-AgNPs provided synergistic neuroprotection by suppressing oxidative stress, inflammation, and ER stress while enhancing antioxidant and anti-apoptotic defenses. Conclusion: These findings suggest that 18 beta-GA-AgNPs may represent a promising therapeutic strategy against diabetes-associated neurodegeneration, although further long-term, ultrastructural, and sex-inclusive studies are warranted.Article Coenzyme Q10 Protects Against Glyphosate-Based Herbicide-Induced Testicular and Sperm Toxicity by Modulating Nrf2/Keap1 and Tlr4/Nf-κb Pathways(Springer, 2025) Mutluay, Duygu; Ozbek, Kader Coban; Tenekeci, Gozde Yucel; Gungor, Sukru; Yakut, Seda; Denk, Baris; Kara, AdemRoundup, the most widely used glyphosate-based herbicide (GBH), contains glyphosate (GLY) as its main active ingredient and was used to model GBH-induced reproductive toxicity in this study. We aimed to investigate the protective effect of coenzyme Q10 (CoQ10) against GLY-induced testicular and sperm damage, focusing on oxidative stress, inflammation, and apoptosis. Unlike previous studies, this work provides the first integrated evidence combining histopathological, biochemical, hormonal, and molecular assessments with functional sperm analyses, and uniquely demonstrates how CoQ10 modulates both antioxidant (Nrf2/Keap1/HO-1) and inflammatory (TLR4/NF-kappa B) pathways in GBH-induced testicular injury. Forty-two adult male ICR mice were assigned to five groups: control, sham, CoQ10 (200 mg/kg/day), GLY (500 mg/kg/day), and GLY + CoQ10 (500 + 200 mg/kg/day). The treatments were administered orally for 35 days, corresponding to one spermatogenesis cycle. GLY reduced testicular weight, disrupted histoarchitecture, increased oxidative stress (up arrow MDA, TOS, OSI; down arrow GSH, TAS), suppressed Nrf2/Keap1/HO-1 signaling, upregulated TLR4/NF-kappa B, and triggered apoptosis (up arrow Bax, down arrow Bcl-2). It also impaired sperm parameters (concentration, motility, morphology, viability, membrane integrity) and increased mitochondrial ROS, while reducing testosterone and elevating LH. CoQ10 co-treatment alleviated these alterations by restoring redox balance, normalizing signaling pathways, improving sperm quality, and correcting hormonal changes. In conclusion, CoQ10 mitigates GLY-induced testicular toxicity by modulating oxidative stress, inflammation, and apoptosis, highlighting its novel therapeutic potential for protecting male fertility against GBH exposure.Article Evaluation of the Toxicological Effects of Favipiravir (t-705) on Liver and Kidney in Rats: Biochemical and Histopathological Approach(Taylor & Francis Ltd, 2023) Kara, Adem; Yakut, Seda; Caglayan, Cuneyt; Atcali, Tugce; Ulucan, Aykut; Kandemir, Fatih MehmetFavipiravir is a selective RNA polymerase inhibitor and a broad-spectrum antiviral drug, an important agent used in viral infections, including Ebola, Lassa, and COVID-19. This study aims to evaluate the potential toxicological effects of favipiravir administration on rats' liver and kidney tissues. Favipiravir was applied for five and ten days in the present study. During this period, it was aimed to determine possible toxic effects on the liver and kidney. For this purpose, the impact of favipiravir on liver and kidney tissues were examined using histopathologic and biochemical methods. The present study showed that favipiravir administration led to an elevation in the liver and kidney serum enzymes and oxidative and histopathologic damages. Favipiravir administration caused apoptotic cell death (Caspase-3 and Bcl-2), inflammation (NF-kappa B and IL-6), and a decrease in renal reabsorption (AQP2) levels. In the evaluation of the findings obtained in this study, it was determined that the favipiravir or metabolites caused liver and kidney damages.Article Histopathological and Biochemical Effects of 18β-Glycyrrhetinic Acid Application on Lipopolysaccharide-Induced Kidney Toxicity in Rats(2024) Yakut, Seda; Gelen, Volkan; Erbaş, Elif; Albayrak, KevserLipopolysaccharide (LPS) is an endotoxin found in the wall of gram-negative bacteria and causes acute inflammation when it enters the tissues. 18β-glycyrrhetinic acid (18β-GA) is a substance found in licorice root and is responsible for this plant's antiallergic, antioxidant, and anti-inflammatory activity. This study aimed to examine the possible effects of 18β-glycyrrhetinic acid on the damage caused by LPS in kidney tissue. The study divided 40 Sprague Dawley adult male rats into 5 equal groups (n = 8). The groups were created as follows; the control group; the group that received 1cc physiological saline throughout the experiment was the DMSO group; DMSO, an intraperitoneal carrier substance, was given. LPS group; A single dose of 7.5 mg/kg intraperitoneal (i.p) LPS was administered. 18β-GA50+LPS group; 18β-glycyrrhetinic acid was given by gavage at 50 mg/kg daily for 10 days, followed by a single dose of 7.5 mg/kg i.p. LPS was administered. 18β-GA100+LPS group; 18β-glycyrrhetinic acid was administered by gavage at 100 mg/kg daily for 10 days, followed by a single dose of 7.5 mg/kg i.p. LPS was administered. 18β-GA100 group; 18β-glycyrrhetinic was given by gavage at 100 mg/kg daily for 10 days. 24 hours after LPS application to all groups, the kidney tissues of the rats were removed under anesthesia and placed in 10% formaldehyde. Histopathological and oxidative stress parameters analyses were performed in kidney tissue. These findings raised the possibility that 18β-GA could be an adjuvant therapy that protects kidney tissue from LPS-induced oxidative and tissue damage effects and reduces its side effects.Article Oleuropein Modulates Behavioral Changes, Apoptosis, Autophagy, Inflammation, Oxidative Stress-Associated PI3K/Akt Pathways in TAA-Induced Hepatic Encephalopathy(Springer/Plenum Publishers, 2026) Yakut, Seda; Kara, Hulya; Ozkanlar, Seckin; Kiziloglu, Halime Topal; Aki, Ruveyda Hilal; Aktas, Buse; Kara, AdemHepatic encephalopathy (HE), which develops as a result of liver failure, is an important neurological disorder involving inflammation and oxidative damage, with apoptosis and autophagy supported mainly by experimental evidence. In the current research, we researched the protective effects of oleuropein (OLE) in a thioacetamide (TAA)-induced HE model, particularly through the PI3K/Akt/mTOR signalling pathway. To execute the planned experimental design, Sprague Dawley rats (n = 28) were divided into four groups: Control, OLE, TAA, and TAA + OLE. OLE was administered orally (50 mg/kg) during a 14-day period, followed by intraperitoneal TAA (50 mg/kg) for 14 days in the TAA groups. Behavioral tests (open field and Y-maze) were used to determine cognitive and anxiety-like disorders in the rats. Oxidative stress indicators (MDA, SOD, and GSH), pro-inflammatory cytokines (IL-1 beta, IFN-gamma, and TNF-alpha), autophagic and apoptotic processes (Caspase-3, Bcl-2, Beclin-1, LC3), PI3K/Akt/mTOR pathway proteins, and AQP4 levels were analyzed in the serum and tissue. Histopathological evaluation was used to evaluate tissue damage in the liver and brain. The results indicated that the TAA-activated PI3K/Akt/mTOR pathway was suppressed by OLE, oxidative damage, autophagy, apoptosis, and inflammation were reduced, and behavioral and histological improvements were achieved. These results suggest that OLE offers hepatoprotective effects and ameliorates HE-associated brain injury via the PI3K/Akt/mTOR pathway.Article Protective Effects of Bromelain in Testicular Torsion-Detorsion: Reducing Inflammation, Oxidative Stress, and Apoptosis While Enhancing Sperm Quality(MDPI, 2025) Yakut, Seda; Karabulut, Merve; Koca, Recep Hakki; Erbas, Elif; Ozkanlar, Seckin; Gencer, Berrin Tarakci; Kumar, K. J. SenthilInflammation and increased oxidative stress in testicular tissue are documented side effects of torsion of the testicles. The preventive role of Bromelain (Bro) against testicle torsion-induced ischemia/reperfusion (I/R) injury was investigated in this research. Five groups of six animals each were created: ischemia, Ischemia+Reperfusion (I+R), Ischemia+Reperfusion+Bromelain (I+R+Bro; 10 mg/kg), control (sham), and Bromelain (Bro; 10 mg/kg). An I/R damage resulted from two hours of 720 degrees clockwise twisting of the left testis. Blood samples and epididymal sperm were collected after reperfusion to analyze sperm parameters (recovery, motility, viability, and morphology) and cytokines that promote inflammation (IL-1 beta, IL-6, and TNF-alpha). Using Western blotting, testicular tissue was examined for histopathological alterations, antioxidant enzymes (GSH, SOD), lipid peroxidation (MDA), apoptosis, and survival-related proteins (TLR4, Caspase-3, Bcl-2, NRF-2, HO-1, PI3K, mTOR, AKT-1). While raising the activities of GSH and SOD, two antioxidant enzymes, Bro administration dramatically reduced MDA concentrations. The I+R+Bro group had significantly reduced amounts of cytokines that promoted inflammation compared to the I+R group. Bro's protective properties are also attributed to proteins that are altered by it and participate in the apoptosis and survival of cells. Sperm morphology, motility, and concentration notably improved in the bromelain-treated group, according to spermatological examination. Testicular samples treated with bromelain showed less tissue damage according to histological evaluations than the untreated I+R group. These findings imply that Bro has anti-inflammatory, anti-apoptotic, and antioxidant qualities. It effectively reduces oxidative stress and inflammation by modulating the PI3K/Akt/mTOR and NRF-2/HO-1 pathways, hence minimizing I/R injury.

