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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 Effects of Systemic Administration of Cisplatin and Hydrogen Sulfide on Cerebrum and Cerebellum Tissue in Rats(Karger, 2021) Polat, Seyhan; Ozhan, Onural; Parlakpinar, Hakan; Durak, Mehmet Akif; Vardi, Nigar; Yildiz, Azibe; Turkoz, Yusuf[Abstract Not Available]Öğe Estimation of the Factors Associated with Diabetes Mellitus by Multilayer Perceptron Artificial Neural Network Model(Karger, 2021) Polat, Seyhan; Parlakpinar, Hakan; Colak, Cemil[Abstract Not Available]Öğe Kupa Tedavisine Genel Bir Bakış(2020) Parlakpınar, Hakan; Polat, SeyhanÖz: Kupa tedavisi, binlerce yıllık uygulanma geçmişi ve bilgi birikimiyle günümüze ulaşmış, koruyucu ve tedavi edici özellikli tamamlayıcı tıp uygulamalarından birisidir. Günümüzde kupa tedavisi dünyanın birçok farklı bölgesinde yaygın bir şekilde uygulanmaktadır. Bazı Avrupa ülkelerinde kupa tedavisi, konvansiyonel sağlık sistemine dâhil edilmiştir. Romatoid artrit, hipertansiyon, baş ağrısı, fibromiyalji, bel ağrısı, osteoartrit, miyofasiyal ağrı sendromu ve infertilite gibi birçok farklı endikasyonda tedavi amacıyla ve sağlıklı bireylerde immün sistemi güçlendirmek için kupa tedavisi uygulanabilmektedir. Geniş bir yelpazedeki tıbbi endikasyonlarda uygulanabilen kupa tedavisinin analjezik, anti-inflamatuar, antioksidan vb. birçok etkiye aracılık ettiği düşünülen farklı görüşler ortaya atılmıştır. Taibah teorisi, kapı kontrol teorisi, diffüz noksiyöz inhibitör kontroller, refleks zon teorisi, ?-endorfin ve adrenokortikal hormonların salınımı, immün sistem aktivasyonu, nitrik oksit teorisi, dolaşımın detoksifikasyonu teorisi, oksidatif stresin azaltılması, miyofasiyal dekompresyon ve plasebo etkinlik öne sürülen mekanizmalardandır. Literatürde, kupa tedavisinin deneysel ve klinik etkililiğini, güvenliliğini ve etki mekanizmalarını derinlemesine tartışan çalışmaların sayısı yeterli değildir. Bu bağlamda, kupa tedavisinde altta yatan mekanizmalar, ortaya atılan bazı teorilere rağmen henüz tam olarak aydınlatılamamıştır. Özetle bu derlemede kupa tedavisinin tarihi, güncel sınıflaması, ileri sürülen etki mekanizmaları ve kullanıldığı hastalıklar güncel literatür verilerinin kılavuzluğunda anlatılmış olup bu uygulamayla ilgili ülkemizdeki yasal durum ifade edilmiştir. Kupa tedavisinin bilimsel yönleriyle tam olarak anlaşılabilmesi için iyi dizayn edilmiş ileri klinik çalışmalara ihtiyaç olduğu iyi bilinen bir gerçektir.Öğe Pharmacological agents under investigation in the treatment of coronavirus disease 2019 and the importance of melatonin(Wiley, 2021) Parlakpinar, Hakan; Polat, Seyhan; Acet, Haci AhmetCoronavirus disease 2019 (COVID-19) is a life-threatening infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 pandemic causing morbidities and even deaths worldwide revealed that there is urgent need to find pharmacological agents or vaccines. Although there are a lot of agents under investigation, there is no approved agent for the prevention or treatment of the COVID-19 yet. Treatment of patients remains mainly supportive as well as compassionate use of the agents under investigation. It is well established that excessive inflammatory and immune response and oxidative injury play a critical role in the pathogenesis of COVID-19. In this review, we aimed to update knowledge about pathogenesis, clinical features, and pharmacological treatment of COVID-19 and review the potential beneficial effects of ancient antioxidant, anti-inflammatory, and immunomodulatory molecule melatonin for prevention and treatment of COVID-19.Öğe Sıçanlarda monokrotalinle oluşturulmuş pulmoner arteriyel hipertansiyon modelinde alamandin ve melatonin'in etkilerinin araştırılması(İnönü Üniversitesi, 2021) Polat, Seyhan; Parlakpınar, HakanAmaç: PAH güncel tedavilere rağmen progresif ve fatal seyretmektedir. Çalışmamızda, kardiyovasküler hastalıklarda faydalı etkileri daha önce gösterilen ALA, MEL ve ALAMEL kombinasyonunun PAH'taki olası koruyucu etkilerinin karşılaştırılması amaçlandı. Gereç ve Yöntem: 10 haftalık erkek sıçanlar, basit randomize olarak kontrol (n=10), MCT (n=12), ALA (n=12), MEL (n=12) ve ALAMEL (n=12) gruplarına ayrıldı. 1. gün 60 mg/kg tek doz sc MCT ile PAH oluşturulurken; 1-35. günler arasında ALA grubuna 50 ?g/kg/gün ip ALA, MEL grubuna 10 mg/kg/gün ip MEL ve ALAMEL grubuna ise ALAMEL kombinasyonu uygulandı. Deney sonunda ekokardiyografik ve invazif hemodinamik ölçümler yapıldı. Kalp ve akciğer dokuları alınarak morfometrik, histopatolojik, ELISA ve western blot analizleri gerçekleştirildi. Bulgular: RV/LV, MCT grubunda artarken; ALA ve ALAMEL gruplarında azalmış bulundu. RVSP, MCT grubunda artarken; MEL grubunda düşme eğiliminde bulundu. MCT grubunda RV/LV+IVS artmış olup; MEL grubunda azalmış bulundu. Tüm tedavi gruplarında, inflamatuvar infiltrasyonda, TIM kalınlığı (p<0,0001) ile PCNA ve ?-SMA immünoreaktivitesinde azalma izlendi. Histopatolojik iyileşme MEL ve ALAMEL gruplarında ALA grubuna göre daha belirgindi. Artan LOX aktivitesi, tüm tedavi gruplarında MCT grubuna kıyasla azalırken; bu azalışın MEL grubunda ALA grubuna göre daha belirgin olduğu bulundu. Sonuçlar: ALA ve özellikle MEL'in antiinflamatuvar, antiproliferatif ve antiremodeling etkileriyle PAH gelişimini azalttığı, ALAMEL kombinasyonunun ise ek fayda sağlamadığı bulundu. ALA ve özellikle MEL'in, LOX inhibisyonuyla ECM remodelingini azaltmasının PAH'ın önlenmesinde önemli olduğu düşünülmektedir. Sonuçlarımızı destekleyecek ileri çalışmalara ihtiyaç vardır.
