Browsing by Author "Bayir, Mehmet Hafit"

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Doksorubisin Kaynaklı Karaciğer Hasarında Oksidatif Stres, Apoptoz ve Değişen Trpm2 Kanalı Aktivasyonunun Rolü; Selenyumun Koruyucu Etkisi
(2024) Yıldızhan, Kenan; Huyut, Zübeyir; Altındag, Fıkret; Bayir, Mehmet Hafit
Amaç: Doksorubisin (DOXR) çeşitli kanser türlerinin tedavisinde sıklıkla tek başına veya kombinasyon terapisi olarak kullanılmaktadır.doza bağlı olarak değişen yan etkiler bilinmesine rağmen, karaciğer sağlığı üzerindeki etkileri tam olarak bilinmemektedir. Bu araştırma, DOXR ile tedavi edilen sıçanlarda geçici reseptör potansiyeli melastatin-2 (TRPM2) kanalının rolünü, TRPM-2 kanal blokörü N-(p-amilsinamoil) antranilik asit (ACA) kullanarak araştırmayı ve selenyum (Se)'un koruycu etkilerini araştırmayı amaçladı. Yöntemler: Sıçanlar altı gruba ayrıldı (n=10): kontrol, DMSO, DOXR, DOXR + Se, DOXR + ACA ve DOXR + ACA + Se. Serum AST, ALT, LDH, trigliserit ve total kolesterol seviyeleri ölçüldü. Ayrıca, karaciğer dokusunda TRPM2 kanalı, 8-OHdG ve kaspaz-3 (Casp-3) ekspresyonları için immünohistokimyasal testler ve ayrıca histopatolojik değerlendirme yapıldı. Bulgular: Serum AST, ALT, LDH, trigliserid ve total kolesterol seviyeleri ve ayrıca karaciğer 8-OHdG, TRPM2 kanalı ve Casp-3 ekspresyonları DOXR grubunda DOXR + Se, DOXR + ACA ve DOXR + ACA + Se gruplarına göre anlamlı derecede yüksekti (p <0.05). Ancak, bu parametreler Se ve ACA ile tedavi edilen gruplarda DOXR grubuna kıyasla önemli ölçüde düşmüştü (p <0.05). Sonuç: Sonuçlar, Se veya ACA'nın DOXR ile eşzamanlı uygulanmasının, DOXR kaynaklı hepatotoksisiteyle mücadelede etkili bir terapötik yaklaşım sağlayabileceğini göstermektedir.
Effect of Hesperidin on Lipid Profile, Inflammation and Apoptosis in Experimental Diabetes
(Maik Nauka/interperiodica/springer, 2025) Yildizhan, Kenan; Bayir, Mehmet Hafit; Huyut, Zuebeyir; Altindag, Fikret
In recent years, therapeutic approaches against diabetes-induced liver damage have attracted great interest. Studies indicate the anticarcinogenic, anti-inflammatory, antioxidant, and lipid-lowering potential of hesperidin (HESP), a flavonoid in citrus fruits. This study examined how HESP prevented streptozotocin (STZ)-induced diabetic liver damage. Four groups of seven rats each were created: Control, HESP (100 mg/kg/day), STZ (45 mg/kg), and STZ + HESP (45 mg/kg and 100 mg/kg/day, respectively). Serum AST, ALT, LDH, LDL, triglyceride, total cholesterol levels, and the TNF-alpha, IL-1 beta, and caspase-3 expression levels of liver tissue in the STZ group were higher than the other groups (p < 0.05). However, these values were significantly lower (p < 0.05) in the STZ + HESP group compared to the STZ group. Furthermore, administering HESP together with STZ reduced liver expression levels of caspase-3, TNF-alpha, and IL-1 beta, as well as blood levels of AST, ALT, LDH, LDL, triglyceride, and total cholesterol. HESP against diabetes-induced hepatic damage reduced proinflammatory cytokine levels, and returned the lipid profile, and apoptotic indicators to normal levels. These findings suggested that HESP therapy may be an important therapeutic role against diabetes-induced liver damage.
Effect of Hesperidin on Sciatic Nerve Damage in Stz-Induced Diabetic Neuropathy: Modulation of Trpm2 Channel
(Springer, 2023) Bayir, Mehmet Hafit; Yildizhan, Kenan; Altindag, Fikret
Diabetic neuropathy (DNP) is a severe complication of diabetes mellitus. In this study, we examined the potential of hesperidin (HES) to attenuate DNP and the involvement of the TRPM2 channel in this process. The rats were given a single dose of 45 mg/kg of streptozotocin (STZ) intraperitoneally to induce diabetic neuropathic pain. On the third day, we confirmed the development of diabetes in the DNP and DNP + HES groups. The HES groups were treated with 100 mg/kg and intragastric gavage daily for 14 days. The results showed that treatment with HES in diabetic rats decreased STZ-induced hyperglycemia and thermal hyperalgesia. Furthermore, in the histopathological examination of the sciatic nerve, HES treatment reduced STZ-induced damage. The immunohistochemical analysis also determined that STZ-induced increased TRPM2 channel, type-4 collagen, and fibrinogen immunoactivity decreased with HES treatment. In addition, we investigated the TRPM2 channel activation in the sciatic nerve damage mechanism of DNP model rats created by STZ application using the ELISA method. We determined the regulatory effect of HES on increased ROS, and PARP1 and TRPM2 channel activation in the sciatic nerves of DNP model rats. These findings indicated that hesperidin treatment could attenuate diabetes-induced DNP by reducing TRPM2 channel activation.
The Effect of Selenium Against Cadmium-Induced Nephrotoxicity in Rats: The Role of the Trpm2 Channel
(Mdpi, 2025) Keles, Omer Faruk; Bayir, Mehmet Hafit; Cicek, Haci Ahmet; Ahlatci, Adem; Yildizhan, Kenan
This study investigated the protective effect of selenium (Se) in a cadmium (Cd)-induced nephrotoxicity model in rats and the role of the TRPM2 channel in this mechanism. For this purpose, Cd (25 mg/kg orally), Se (0.5 mg/kg i.p.), and 2-aminoethoxydiphenyl borate (2-APB), a TRPM2 channel antagonist, (3 mg/kg i.p.) were administered to rats every day for 5 days. At the end of the study, kidney tissues were analysed using histological and biochemical methods. A histopathological examination revealed congestion, tubular degeneration, necrosis, and glomerular adhesion in the Cd group. However, these lesions were significantly reduced in the Cd + Se and Cd + 2-APB groups, while the Cd + Se + 2-APB group showed a histological appearance similar to the control group. Immunohistochemical analysis revealed that Caspase-3, Bax, and TRPM2 expression was higher in the Cd group, while these levels were lower in the Se and 2-APB treatment groups (p < 0.05). Among the groups that received Cd, urea, creatinine, TOS, TNF-alpha, and IL-1 beta levels were at the highest level in the Cd group, while TAS level was at the lowest level (p < 0.05). The Se and 2-APB treatment modulated these parameters; however, Se + 2-APB treatment reduced urea, creatinine, TOS, TNF-alpha, and IL-1 beta levels to the lowest level compared to the Cd groups and brought the TAS level closer to the control group (p < 0.05). These findings indicated that targeting TRPM2 channel inactivation together with the selenium treatment could alleviate Cd-induced nephrotoxicity.
Evaluation of the Relationship Between Histopathological Findings in Appendectomy Specimens and Enterobius Vermicularis Infection
(Erciyes Univ Sch Medicine, 2023) Aydemir, Selahattin; Gumus, Meryem; Inceman, Merve; Cengiz, Zeynep Tas; Bayir, Mehmet Hafit; Yilmaz, Hasan
Objective: This study aimed to assess the relationship between Enterobius vermicularis and appendicitis by determining the frequency of E. vermicularis in appendectomy specimens obtained after a preliminary diagnosis of appendicitis. Materials and Methods: Retrospective evaluation was conducted on the results of appendectomy specimens examined histopathologically at Van Training and Research Hospital Pathology Laboratory from March 2016 to March 2022. Hematoxylin-eosin stained slides from 7,814 appendectomy specimens were scrutinized for the presence of E. vermicularis, acute inflammation, fecaloid material, lymphoid hyperplasia, obliteration, perforation, phlegmonous appendicitis, and peritonitis. Furthermore, slides stained with hematoxylin-eosin (H&E) from patients testing positive for E. vermicularis were re-evaluated by the author in pathology.Results: E. vermicularis was identified in the appendectomy specimens of 50 (0.64%) out of 7,814 patients who underwent appendectomies. In histopathological examina-tions, the occurrence of lymphoid hyperplasia and fibrous obliteration was higher in E. vermicularis-positive patients compared to those who teste negative. Findings revealed that the mean white blood cell count (WBC) was lower in E. vermicularis-positive patients than in negative patients, while the mean eosinophil percentage (EO%) was higher.Conclusion: These findings imply that although the parasite is not a direct causative factor for appendicitis, it may contribute to the development of factors that result in obstruction in certain cases.
Investigation of the Effects of Hesperidin on the Sciatic Nerve in an Experimental Diabetes Model Created by Streptozotocin
(2023) Bayir, Mehmet Hafit; Altındağ, Fikret; Yıldızhan, Kenan
Diyabetik nöropati (DNP), diyabet sendromunun önemli bir komplikasyonudur. Hesperidin (HES) anti-inflamatuar, anti-kanserojen, anti-oksidan özeliği bilinen bir flavonoiddir. Bu çalışmada, sıçanlarda streptozotosin (STZ) ile oluşturulan DNP modelinde HES'in koruyucu etkisinin araştırılması amaçlanmıştır. Çalışmada 28 adet Wistar Albino sıçan dört gruba ayrıldı (n=7); kontrol, HES, DNP ve DNP+HES. DNP gruplarına çalışma başlangıcında (0. gün) STZ (45 mg/kg i.p.) uygulandı. Çalışmanın 3. günü tüm grupların kan şekeri seviyeleri ölçülerek, DNP ve DNP+HES gruplarındaki sıçanlarda diyabet oluştuğu doğrulandı. Bundan sonra HES gruplarına 14 gün boyunca 100 mg/kg/gün HES intragastrik (i.g.) yol ile uygulandı. Çalışma süresince (0., 3., 10., ve 17. günlerde) ortalama kan şekeri seviyesi ölçümü, ortalama ağırlık değişimi, kuyruk kaldırma ve sıcak plaka testleri yapıldı. Çalışma sonunda sıçanlardan alınan siyatik sinir örneklerinde histopatolojik, stereolojik ve immünohistokimyasal olarak değerlendirildi. Bulgularımıza göre; 17. günün sonunda kontrol ile kıyaslandığında DNP grubunun kuyruk kaldırma ve sıcak plaka testi sürelerinin anlamlı düzeyde kısaldığı görüldü. DNP+HES grubunun kuyruk kaldırma ve sıcak plaka testi süreleri kontrol grubuna kıyasla anlamlı düzeyde kısalırken, DNP grubuna kıyasla daha uzun olduğu gözlemlendi. Hematoksilen-eozin (HE) ve toluidin blue (TB) ile yapılan incelemede kontrol ve HES gruplarında siyatik sinir normal histolojik yapıda görülürken, DNP grubunda endonöral yapıda bozulma ve aksonlarda dejenerasyon görüldü. DNP+HES grubu DNP grubuyla kıyaslandığında daha aksonlarda daha az dejenarasyon ve endonöral yapının daha düzenli olduğu görüldü. Stereolojik incelemede, DNP grubundaki siyatik sinirlerde akson sayısının anlamlı derecede azaldığı görüldü. Kontrol, HES ve DNP+HES grupları arasında ise toplam akson sayıları arasında anlamlı bir farka rastlanılmadı. Gruplar arasında, immünohistokimyasal değişimler incelendiğinde ise DNP grubunda yoğun tip 4 kolajen ve fibrinojen ekspresyonuna rastlanırken, Kontrol, HES ve DNP+HES gruplarında düşük tip 4 kolajen ve fibrinojen ekspresyonuna rastlandı. Sonuç olarak, çalışmamızın bulguları HES tedavisinin STZ kaynaklı DNP hasar mekanizmalarını baskılayarak ağrı eşiğini ve kan şekeri seviyesini düzelttebileceğini, siyatik sinirlerde dejenerasyonu, tip 4 kolajen ve fibrinojen ekspresyonunu azalttabileceğini ortaya koymaktadır.
Selenium Reduces Cadmium-Induced Cardiotoxicity by Modulating Oxidative Stress and the ROS/PARP-1/TRPM2 Signalling Pathway in Rats
(Multidisciplinary Digital Publishing Institute (MDPI), 2025) Yazğan, Yener; Keleş, Omer Faruk; Bayir, Mehmet Hafit; Çi̇çek, Hacı Ahmet; Ahlatci, Adem; Yıldızhan, Kenan
Cadmium (CAD) is a prevalent environmental contaminant that poses serious cardiotoxic risks. The heart, kidney, liver, and brain are just a few of the essential organs that can sustain serious harm from CAD, a very poisonous heavy metal. The cardiotoxic mechanism of CAD is linked to oxidative damage and inflammation. A trace element with anti-inflammatory, anti-apoptotic, and antioxidant qualities, selenium (SEL) can be taken as a dietary supplement. The biotoxicity of heavy metal CAD is significantly inhibited by SEL, a mineral that is vital to human and animal nutrition. Through ROS-induced PARP-1/ADPR/TRPM2 pathways, this study seeks to assess the preventive benefits of selenium against cardiovascular damage caused by CAD. The SEL showed encouraging results in reducing inflammatory and oxidative reactions. Rats were given 0.5 mg/kg SEL and 3 mg/kg 2-Aminoethyl diphenylborinate (2-APB) intraperitoneally for five days, in addition to 25 mg/kg CAD given via gavage. Histopathological examination findings revealed that the morphologic changes in the hearts of the CAD group rats were characterised by marked necrosis and the degeneration of myocytes and congestion of vessels. Compared to the rats in the CAD group, the hearts of the SEL, 2-APB and SEL+2-APB groups showed fewer morphological alterations. Moreover, in rats given CAD, there was an increase in cardiac malondialdehyde (MDA), total oxidant (TOS), reactive oxygen species (ROS), caspase (Casp-3-9), and TNF-α, whereas glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and total antioxidant (TAS) decreased. SEL improved antioxidants, avoided tissue damage, and reduced cardiac MDA, TOS, and ROS. In rats given CAD, SEL decreased cardiac PARP-1, TRPM2, TNF-α, and caspase. In summary, by reducing oxidative stress and cardiac damage and modifying the ROS/PARP-1/TRPM2 pathway, SEL protected against CAD cardiotoxicity. © 2025 Elsevier B.V., All rights reserved.