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Öğe The Effect Of L-Carnitine And Alpha Lipoic Acid Administration With Exercise In Old Rats On Energy Metabolism Related To Oxidative Stress Parameters(Marmara Univ, Inst Health Sciences, 2024) Kalkan, Kardelen Kocaman; Sirin, Neslihan; Tepe, Atakan; Gok, Ali; Altas, Tolga; Agan, Kagan; Gulhan, Pinar YildizObjective: This study aims to contribute novel insights by investigating the potential positive effects of a combined dietary supplement and exercise program on mitochondrial oxidative stress and energy metabolism in aging. Focusing on the protective impact of Alpha Lipoic Acid (ALA), a potent antioxidant, against exercise-induced mitochondrial oxidative stress in rats, we also assess how L-Carnitine administration affects exercise ability by analyzing resistin and HbA1c levels, indicators linked to insulin resistance and cellular sensitivity. Method: In this 10-day study, 42 old male Sprague Dawley rats (weighing 400 +/- 10 g, aged 15-17 weeks) were divided into six groups (n=7): Control, Exercise, L-Carnitine, Alpha Lipoic Acid (ALA), L-Carnitine+Exercise, ALA+Exercise. Relevant groups received daily oral gavage doses of L - Carnitine (50 mg/ml) and ALA (18 mg/ml). Exercise groups underwent treadmill sessions. On day 10, blood samples were quantitatively analyzed for HbA1c and Resistin levels using a Cusabio ELISA assay kit (China). Results: ALA supplementation synergistically reduced resistin and HbA1c levels, individually and combined with exercise. Conversely, L-Carnitine supplement, alone or with exercise, increased resistin levels but it caused a decrease in HbA1c levels. Conclusion: The data indicated a minor, insignificant decrease in resistin levels for the exercise and ALA groups, with a statistically significant difference in HbA1c levels among all groups. Exercise alone positively impacted both HbA1c and resistin levels, suggesting a potential counteraction of age-related oxidative stress and a positive influence on energy metabolism through an appropriate diet and exercise program. Further studies are required to explore specific metabolic pathways and relationships identified in our findings.Öğe Investigation of Total Phenolic Content of Tilia dasystyla and Polygonatum orientale Desf Extracts and Their Cytotoxic Effect on the Osteogenic Sarcoma (Saos-2) Cancer Cell Line(Kowsar Publ, 2020) Zarringhalami, Roshanak; Hanachi, Parichehr; Kaya, Ertugrul; Agan, Aydan Fulden; Agan, Kagan; Donmez, MertBackground: Osteosarcoma; is one of the most common malignant tumors. Nowadays, because of the many side effects of cancer drugs, the usage of herbal medicine which can inhibit or eliminate cancer cells by their antioxidant compounds is increased. Objectives: In the present study anticancer effect of Tilia dasystyla and Polygonatum orientale Desf different extracts on osteogenic sarcoma (Saos-2) cancer cell line was investigated and their polyphenolic compounds were identified by liquid chromatography-mass spectrometry (LC-MS) analysis. The cytotoxic effect of these extracts on Saos-2 cell line and identification of their phenolic compounds have not been reported so far. Methods: Cancer cell lines were provided from Department of Biological Sciences, Bursa University, Turkey. Different concentrations of the methanol, ethanol, and diluted water extracts (0.5 - 5 mg/mL) were tested on Saos-2 cell line. After 24, 48, and 72 hours, the cell viability was evaluated using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. For the investigation of total phenolic compounds of T. dasystyla and P. orientale Desf extracts LC-MS method was applied. Results: According to the results diluted water extracts on the Saos-2 cancer cell line showed more cytotoxic effect than other solvents. The lowest IC50 value was 0.58 +/- 0.01 mg/mL within 72 hours belonged to T. dasystyla water extract. Conclusions: Tilia dasystyla and Polygonatum orientale Desf extracts contain some polyphenolic compounds which showed cytotoxic effect on Saos-2 cancer cell line. The full potential of these herbal extracts is yet to be realized by further studies on animal models and subsequent trials.Öğe Protective Mechanisms of EGCG in Mitigating Oxidative Stress and Liver Toxicity From Cigarette Smoke-Induced Damage(Wiley, 2025) Agan, Kagan; Demir, Serif; Ozmerdivenli, Recep; Agan, Aydan Fulden; Akin, Ali Tugrul; Alpay, Merve; Beyazcicek, OzgeExposure to cigarette smoke leads to an increase in oxidative stress within the body, resulting in both an elevated oxidant burden and a compromised antioxidant defense system. This imbalance creates a significant risk factor for various diseases by promoting cellular damage, inflammation, and toxicity. The oxidants present in cigarette smoke are considered the primary contributors to these pathological conditions. Supporting the antioxidant system with specific bioactive compounds may help mitigate the toxic effects caused by cigarette smoke. In this study, the effects of EGCG pre-administration on the antioxidant system were evaluated under both acute and chronic exposure conditions to cigarette smoke. Different doses of EGCG were administered to determine its potential role in oxidative stress regulation, and histopathological examinations and antioxidant enzyme levels were assessed. The findings demonstrated that while acute EGCG administration did not significantly improve antioxidant enzyme activity, chronic administration of EGCG at a dose of 50 mg/kg effectively increased antioxidant enzyme production, reduced oxidative stress, and liver injury. In the presence of cigarette smoke, EGCG contributed to the stabilization of oxidative stress markers. However, chronic EGCG administration in the absence of oxidative stressors requires further investigation to assess its impact on other organs. EGCG appears to be a promising candidate for alleviating the adverse effects of external oxidant exposure and mitigating oxidative stress. However, its long-term application and potential side effects in different physiological conditions should be explored further examinations. Although acute EGCG application did not enhance antioxidant enzyme levels, it unexpectedly elevated oxidative stress, emphasizing the need for more comprehensive studies to clarify its mechanisms and optimize its usage. We further identify the principal underlying mechanisms involved in this process.Öğe State-of-the-art preclinical techniques to study the impact of spreading depolarizations in awake rodents(Bmc, 2025) Labastida-Ramirez, Alejandro; Codadu, Neela K.; Agan, Kagan; Wykes, Robert C.BackgroundUnderstanding the mechanisms of pathological brain network activity and the efficacy of therapies requires testing hypothesis in vivo, where brain circuitry remains preserved. Therefore, animal models are a key tool in the study of primary neurological disorders such as migraine, stroke and epilepsy. These models not only have advanced our understanding of the underlying neurobiology of these disorders but have also provided novel pharmacological targets and insights on shared pathophysiological processes such as spreading depolarizations (SD). SD, the electrographic correlate of migraine with aura, are transient waves of near-complete neuroglial depolarization associated with transmembrane ionic and water shifts.BodyMany studies investigating the impact of SD in preclinical models have done so in the presence of anesthesia. However, the use of anesthesia is a well-known confounding factor that not only influences SD threshold or frequency but also SD-evoked hemodynamic responses as common anesthetics affect cerebral blood flow and neurovascular coupling, limiting translation. Therefore, here we discuss research methods that have recently been developed or refined to allow the study of SD in awake rodents with a focus on migraine with aura. We discuss advantages, limitations and also efforts made to transition towards minimally-invasive procedures. Methods include optogenetic approaches to induce SD, multisite high-fidelity DC-coupled electrophysiological recordings, and measurements of neurovascular signals detected at both mesoscopic/macroscopic (e.g., fluorescent reporters, functional ultrasound system) and microscopic levels (e.g., two-photon microscopy, miniscopes). Additionally, we discuss continuous wireless telemetry recordings to detect spontaneous SD frequency over weeks to months in freely moving animals.ConclusionImplementation of these methods in awake brain will close the translational gap and improve the relevance of preclinical animal models.












