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Öğe Alamandine alleviates methotrexate-induced nephrotoxicity in rats by targeting oxidative stress and inflammation(2023) Yıldız, Azibe; Aras, Muhammed Yasir; Gunata, Mehmet; Durhan, Merve; Polat, Seyhan; Parlakpınar, Hakan; Cigremis, YilmazAim: Nephrotoxicity due to the use of methotrexate (Mtx) is one of the most important problems associated with chemotherapy. Oxidative stress and inflammation are the major pathomechanisms of Mtx-induced nephrotoxicity. Alamandine (Ala), a new member of the renin-angiotensin system (RAS), is an important peptide with antioxidant and antiinflammatory capacities. In this study, it was investigated whether Ala ameliorates Mtxinduced kidney damage by reducing oxidative stress and inflammation. Materials and Methods: Male Wistar albino rats were assigned into three groups: control group, Mtx group, and Mtx+Ala group. At the end of the experiment, kidney tissues were quickly removed. Glutathione (GSH) and malondialdehyde (MDA) levels were measured to determine the oxidative state in kidney tissues. In addition, tissue samples were assessed as histopathological and immunohistochemical for heat shock protein 60 (HSP60), caspase-3, tumor necrosis factor-? (TNF-?), and receptor-interacting protein kinase-3 (RIPK3). Results: Mtx treatment resulted in reduced GSH content, elevated MDA level, increased heat shock protein 60 (HSP60), and caspase-3 expression. These changes in kidney tissues of rats treated with Mtx triggered oxidative stress characterized by apoptosis and kidney damage. Mtx also markedly increased the expression of TNF-?, an inflammation marker, and RIPK3, a marker of necroptosis. However, Ala administration significantly alleviated Mtx-induced kidney damage by reducing apoptosis and necroptosis by suppressing oxidative stress and inflammation. Conclusion: Taken together, our results support that Ala treatment can serve as a new and promising therapeutic strategy against Mtx-induced nephrotoxicity.Öğe Anti-Inflammatory Effects of Resveratrol on the Radiotherapy-Induced Neuroinflammation(2022) Yıldız, Azibe; Ciftci, Tuba; Polat, Seyhan; Gunata, Mehmet; Parlakpınar, Hakan; Temelli, Öztun; Polat, AlaadinObjective: Damage in the central nervous system caused by cranial radiotherapy (RT) has been linked to neuroinflammation due to microglial activation. Evidence reveals that resveratrol (RES) exerts neuroprotective effects by inhibiting neuroinflammation. There are limited studies investigating the effects of RES on microglia-related neuroinflammation developed as a result of RT. Therefore, this study was designed to investigate the effects of RES on RT-induced microglial- related neuroinflammation. Materials and Methods: Rats were simple randomly divided into three groups. Sham (SH) group received ethanol solution on the 1st-14th days of the study. RT group was applied a single dose of total cranial 15 Gy X radiation on the 7th day of the study. RES group was administered a dose of 20 mg/kg on the 1st-14th days of the study and a single dose of total cranial 15 Gy X radiation on the 7th day of the study. The brain tissues removed at the end of the experiment were subjected to histological techniques and procedures for histological and immunohistochemical examinations. The data were evaluated statistically. Results: RT administration caused histological changes such as neuron degeneration and edema in the brain tissue. In addition, RT administration induced a significant increase in CD68 and tumor necrosis factor-alpha (TNF-?) immunoreactivity. In the RES+RT group, it was observed that histological changes were alleviated, and CD68 and TNF-? immunoreactivities were decreased. In addition, a significant increase in the immunoreactivity of autophagy-related proteins was detected in this group. Conclusion: Evaluating together all the data, it was revealed that RES attenuates microglia- mediated neuroinflammation and neuronal degeneration.Öğe Chemical warfare agents and treatment strategies(2018) Parlakpınar, Hakan; Gunata, Mehmet; Polat, SeyhanAbstract: Chemical agents; is the general name of substances known to have toxic effects on the environment, which cause a large number of deaths and disabilities in a short period of time. These agents are divided into subclasses such as blister, nerve, choking, incapacitating/behavior altering, and asphyxiants/blood agents. In addition to the short-term effects of these agents there may be long-term reflections which affect the next generation. The previous century has been an important period in terms of observing the problems arising from the usage of the agents during wars. Deaths only due to nerve agents are thought to exceed 5 millions in recent wars. Especially the situation that the World War II has emerged shows the magnitude of the use of chemical agents. Due to these detrimental effects, their usage is restricted or prohibited by various international organizations. Despite these obstacles, chemical agents have been used by some countries and terrorist groups. Effects of these agents can take part vary from basic symptoms such as nose irritation to serious problems such as respiratory arrest. Healthcare professionals working in the management of exposure to these agents should have sufficient knowledge and be aware of their effects on the body. For this purpose; we discussed the serious effects of chemical warfare agents on human health and environment, post-exposure applications and pharmacological treatment options.Öğe Chemical warfare agents and treatment strategies(2018) Polat, Seyhan; Gunata, Mehmet; Parlakpinar, HakanChemical agents; is the general name of substances known to have toxic effects on the environment, which cause a large number of deaths and disabilities in a short period of time. These agents are divided into subclasses such as blister, nerve, choking, incapacitating/behavior altering, and asphyxiants/blood agents. In addition to the short-term effects of these agents there may be long-term reflections which affect the next generation. The previous century has been an important period in terms of observing the problems arising from the usage of the agents during wars. Deaths only due to nerve agents are thought to exceed 5 millions in recent wars. Especially the situation that the World War II has emerged shows the magnitude of the use of chemical agents. Due to these detrimental effects, their usage is restricted or prohibited by various international organizations. Despite these obstacles, chemical agents have been used by some countries and terrorist groups. Effects of these agents can take part vary from basic symptoms such as nose irritation to serious problems such as respiratory arrest. Healthcare professionals working in the management of exposure to these agents should have sufficient knowledge and be aware of their effects on the body. For this purpose; we discussed the serious effects of chemical warfare agents on human health and environment, post-exposure applications and pharmacological treatment options.Öğe Estimation of Risk Factors Related to Heart Diseases With Multilayer Perceptron Model(2022) Gunata, Mehmet; Arslan, Ahmet Kadir; Çolak, Cemil; Parlakpınar, HakanAim: Heart diseases (HD) refer to many diseases such as coronary heart disease, heart failure, and heart attack. Every year, approximately 647.000 people die in the United States (U.S.) from HD. Genetic and environmental risk factors have been identified due to numerous studies to determine HD risk factors.Material and Method: In this study, the Multilayer Perceptron (MLP) model was constructed to predict the risk factors related to HD in both genders. The relevant dataset consisted of 270 individuals, 13 predictors, and one response/target variable. Model performance was evaluated using overall accuracy, the area under the ROC (Receiver Operating Characteristics) curve (AUC), sensitivity, and specificity metrics.Results: The performance metric values for accuracy, AUC, sensitivity and specificity were obtained with 95% CI, 0.876 (0.79-0.937), 0.935 (0.877-0.992), 0.921 (0.786-0.983) and 0.843 (0.714-0.93), respectively. According to the relevant model findings, blood pressure, the number of significant vessels coloured by fluoroscopy, and cholesterol variables were the three most crucial HD classification factors.Discussion: It can be said that the model used in the present study offers an acceptable estimation performance when all performance metrics are considered. In addition, when compared with the studies in the literature from both data science and statistical point of view, it can be stated that the findings in the current study are more satisfactory.Conclusion: Due to the predictive performance in this study, the MLP model can be recommended to clinicians as a clinical decision support system. Finally, we propose solutions and future research pathways for the various computational materials science challenges for early HD diagnosis.Öğe Experimental heart failure models in small animals(Springer, 2023) Gunata, Mehmet; Parlakpinar, HakanHeart failure (HF) is one of the most critical health and economic burdens worldwide, and its prevalence is continuously increasing. HF is a disease that occurs due to a pathological change arising from the function or structure of the heart tissue and usually progresses. Numerous experimental HF models have been created to elucidate the pathophysiological mechanisms that cause HF. An understanding of the pathophysiology of HF is essential for the development of novel efficient therapies. During the past few decades, animal models have provided new insights into the complex pathogenesis of HF. Success in the pathophysiology and treatment of HF has been achieved by using animal models of HF. The development of new in vivo models is critical for evaluating treatments such as gene therapy, mechanical devices, and new surgical approaches. However, each animal model has advantages and limitations, and none of these models is suitable for studying all aspects of HF. Therefore, the researchers have to choose an appropriate experimental model that will fully reflect HF. Despite some limitations, these animal models provided a significant advance in the etiology and pathogenesis of HF. Also, experimental HF models have led to the development of new treatments. In this review, we discussed widely used experimental HF models that continue to provide critical information for HF patients and facilitate the development of new treatment strategies.Öğe Protective effects of naringin on valproic acid-induced hepatotoxicity in rats(Churchill Livingstone, 2021) Koroglu, Omer Faruk; Gunata, Mehmet; Vardi, Nigar; Yildiz, Azibe; Ates, Burhan; Colak, Cemil; Tanriverdi, Lokman HekimValproic acid (VPA) is mainly prescribed to treat epilepsy. VPA has been reported to be associated with many adverse effects, including hepatotoxicity. Naringin (NRG) is a natural, therapeutically active flavanone glycoside with anti-inflammatory, anti-apoptotic, and antioxidant. The current study was therefore designed to investigate the protective effect of NRG against the VPA-induced experimental hepatotoxicity model. For this purpose, 24 Wistar albino rats were randomly divided into three groups as control (Vehicle), VPA (500 mg/kg), and NRG + VPA (100 mg/kg NRG + 500 mg/kg VPA) groups. The agents were administered via oral gavage for 14 days. Blood and liver tissue samples were taken on the end of the experiment. Biochemical analyzes were performed on the blood and liver samples. Also, malondialdehyde (MDA), superoxide dismutase (SOD) enzyme, glutathione (GSH) content, catalase (CAT) enzyme levels were examined in the liver tissue samples. Histopathological changes (hydropic degeneration and congestion) in the VPA group were increased significantly when compared to the control group (p < 0.05). We also found a decrease in enzymes of serum liver function in the VPA group. However, NRG has been shown not to prevent histopathological changes in the VPA group. According to our results with this experiment protocol, NRG could not exert sufficient protection against VPA-induced hepatotoxicity.Öğe Relationship between Ratio of the Lengths of the Second and Fourth Fingers (2D: 4D) with Cardiovascular System Diseases(Wiley-Blackwell, 2015) Gunata, Mehmet[Abstract Not Available]Öğe A review of myocardial ischaemia/reperfusion injury: Pathophysiology, experimental models, biomarkers, genetics and pharmacological treatment(Wiley, 2021) Gunata, Mehmet; Parlakpinar, HakanCardiovascular diseases are known to be the most fatal diseases worldwide. Ischaemia/reperfusion (I/R) injury is at the centre of the pathology of the most common cardiovascular diseases. According to the World Health Organization estimates, ischaemic heart disease is the leading global cause of death, causing more than 9 million deaths in 2016. After cardiovascular events, thrombolysis, percutaneous transluminal coronary angioplasty or coronary bypass surgery are applied as treatment. However, after restoring coronary blood flow, myocardial I/R injury may occur. It is known that this damage occurs due to many pathophysiological mechanisms, especially increasing reactive oxygen types. Besides causing cardiomyocyte death through multiple mechanisms, it may be an important reason for affecting other cell types such as platelets, fibroblasts, endothelial and smooth muscle cells and immune cells. Also, polymorphonuclear leukocytes are associated with myocardial I/R damage during reperfusion. This damage may be insufficient in patients with co-morbidity, as it is demonstrated that it can be prevented by various endogenous antioxidant systems. In this context, the resulting data suggest that optimal cardioprotection may require a combination of additional or synergistic multi-target treatments. In this review, we discussed the pathophysiology, experimental models, biomarkers, treatment and its relationship with genetics in myocardial I/R injury. Significance of the study This review summarized current information on myocardial ischaemia/reperfusion injury (pathophysiology, experimental models, biomarkers, genetics and pharmacological therapy) for researchers and reveals guiding data for researchers, especially in the field of cardiovascular system and pharmacology.Öğe SARS-COV-2 (COVID-19): Cellular and biochemical properties and pharmacological insights into new therapeutic developments(Wiley, 2021) Parlakpinar, Hakan; Gunata, MehmetCOVID-19 caused by SARS-COV-2 first appeared in the Wuhan City of China and began to spread rapidly among people. Rapid progression of the outbreak has led to a major global public health problem of a potentially fatal disease. On January 30, 2020, WHO declared the pandemic as the sixth public health emergency of the world. Upon this, the whole country has started to take the necessary precautions. The new coronavirus uses membrane-bound angiotensin-converting enzyme 2 (ACE2) to enter into the cells, such as SARS-CoV, and mostly affects the respiratory tract. Symptoms of COVID-19 patients include fever (93%), fatigue (70%), cough (70%), anorexia (40%) and dyspnoea (34.5%). The elderly and people with underlying chronic diseases are more susceptible to infection and higher mortality. Currently, a large number of drugs and vaccines studies are ongoing. In this review, we discussed the virology, epidemiological data, the replication of the virus, and its relationship with cardiovascular diseases on COVID-19 pandemics, treatment and vaccines. Thereby, this study aims to neatly present scientific data in light of many regarding literature that can be a clue for readers who research this disease prevention and treatment. Significance of the study This review summarized current information on COVID-19 (epidemiology, pathophysiology, clinical, laboratory, cardiovascular diseases, ACE2 and pharmacological agents) for researchers and reveals guiding data for researchers, especially in the field of cardiovascular system, pharmacology, dysregulation of cellular function in disease, molecular and cell biology and physiology in the regulation of tissue function in health and disease.Öğe Transplantation and immunosuppression: a review of novel transplant-related immunosuppressant drugs(Taylor & Francis Ltd, 2021) Parlakpinar, Hakan; Gunata, MehmetImmunosuppressive drugs used in the transplantation period are generally defined as induction and maintenance therapy. The use of immunosuppressants, which are particularly useful and have fewer side effects, decreased both mortality and morbidity. Many drugs such as steroids, calcineurin inhibitors (cyclosporine-A, tacrolimus), antimetabolites (mycophenolate mofetil, azathioprine), and mTOR inhibitors (sirolimus, everolimus) are used as immunosuppressive agents. Although immunosuppressant drugs cause many side effects such as hypertension, infection, and hyperlipidemia, they are the agents that should be used to prevent organ rejection. This shows the importance of individualized drug use. The optimal immunosuppressive therapy post-transplant is not established. Therefore, discovering less toxic but more potent new agents is of great importance, and new experimental and clinical studies are needed in this regard. Our review discussed the mechanism of immunosuppressants, new agents' discovery, and current therapeutic protocols in the transplantation.
