Publication: Yüksek yağlı diyetle indüklenmiş obez sıçanlarda aposininin aort üzerine etkisinin ışık ikroskobik ve ince yapısal düzeyde incelenmesi
Abstract
Amaç: Yüksek yağlı diyet (YD) tüketiminden kaynaklanan obezite oksidatif stresle (OS) ilişkili olan ateroskleroz (AS) gelişimi için bir risk faktörüdür. Aposininin (APS) OS’yi baskılayıcı ve anti-aterosklerotik etkisi gösterilmiş, ancak obezite ile ilişkili-AS üzerindeki etkisi net olarak anlaşılamamıştır. Bu çalışmada APS’nin YD ile beslenen obez sıçanların aortu üzerindeki etkilerini ortaya koymak amaçlandı. Gereç ve Yöntem: Wistar albino erkek sıçanlar kontrol (KNT), YD ve YD+APS gruplarına ayrıldı (n=7). YD ve YD+APS grupları 16 hafta boyunca YD ile beslendi. YD+APS grubuna son 4 hafta boyunca haftada 5 gün orogastrik gavaj ile APS (25 mg/ kg) verildi. APS’nin AS ile ilişkili metabolik parametreler (trigliserit, total kolesterol, HDL-kolesterol, insülin ve leptin), OS [malondialdehit, glutatyon, NADPH-oksidaz-2, okside-LDL (ox-LDL) ve 8-hidroksi-2-deoksiguanozin], LDL ve ox-LDL alım potansiyeli (aktivin reseptör benzeri kinaz-1, okside-LDL reseptörü-1), doku inflamasyonu (miyeloperoksidaz, monosit kemoatraktan protein-1, tümör nekroz faktör-alfa), endotelyal disfonksiyon (ED) (endotelyal-nitrik oksit sentaz, uyarılabilir-nitrik oksit sentaz, nitrik oksit), programlı hücre ölümü (terminal-deoksinükleotidil transferaz-dUTP-kırık uç işaretleme, yarıklanmış-poli ADP riboz polimeraz, gasdermin-D N-terminal parçası, kaspaz-1), düz kas hücre dönüşümü (alfa-düz kas aktini), torasik aort histolojisi ve ince yapısı üzerine etkileri histokimyasal, immunohistokimyasal, elektron mikroskopik ve moleküler yöntemler yardımıyla değerlendirildi. Bulgular: APS, obezitede metabolik parametreler, OS, inflamasyon, ED, programlı hücre ölümü, ox-LDL alım potansiyeli üzerinde iyileştirici etki gösterirken, köpük hücre oluşumu ve LDL alım potansiyeli üzerinde etki göstermedi. Sonuç: Aposinin, aterosklerozun erken evresine katılan oksidatif stres ile ilişkili faktörleri baskılayarak obezitedeki endotelyal disfonksiyon ve ateroskleroz patolojisini iyileştirebilir.
Objective: Obesity resulting from high-fat diet (HD) consumption is a risk factor for the development of atherosclerosis (AS), which is associated with oxidative stress (OS). Apocynin (APC) has been shown to have oxidative stress suppressive and anti-atherosclerotic effects, but its effect on obesity-associated AS is not clearly understood. This study aimed to reveal the effects of APC on the aorta of obese rats fed with a HD. Materials and Methods: Male Wistar albino rats were divided into control (CNT), HD and HD+APC groups (n = 7). HD and HD+APC groups were fed with a HD for 16 weeks. APC (25 mg/ kg) was given to the HD+APC group by orogastric gavage 5 days a week for the last 4 weeks. The effect of APC on atherosclerosis-related metabolic parameters (triglyceride, total cholesterol, HDL-cholesterol, insulin and leptin), OS [malondialdehyde, glutathione, NADPH oxidase-2, oxidized-LDL (ox-LDL) and 8-hydroxy-2-deoxyguanosine], LDL and ox-LDL uptake potential (activin receptor-like kinase-1, oxidized-LDL receptor-1), tissue inflammation (myeloperoxidase, monocyte chemoattractant protein-1, tumor necrosis factor-alpha), endothelial dysfunction (ED) (endothelial-nitric oxide synthase, inducible-nitric oxide synthase, nitric oxide), programmed cell death (terminal-deoxynucleotidyl transferase-dUTP nick end labeling, cleaved-poly ADP ribose polymerase, gasdermin-D N-terminal fragment, caspase-1), smooth muscle cell transformation (alpha-smooth muscle actin), thoracic aorta histology and ultrastructure were evaluated using different methods. Results: While APC showed an ameliorating effect on metabolic parameters, OS, inflammation, ED, programmed cell death, and ox-LDL uptake potential, it had no effect on foam cell formation and LDL uptake potential in obesity. Conclusion: Apocynin may improve the pathogenesis of endothelial dysfunction and atherosclerosis in obesity by suppressing oxidative stress-related factors involved in the early stage of atherosclerosis.
Objective: Obesity resulting from high-fat diet (HD) consumption is a risk factor for the development of atherosclerosis (AS), which is associated with oxidative stress (OS). Apocynin (APC) has been shown to have oxidative stress suppressive and anti-atherosclerotic effects, but its effect on obesity-associated AS is not clearly understood. This study aimed to reveal the effects of APC on the aorta of obese rats fed with a HD. Materials and Methods: Male Wistar albino rats were divided into control (CNT), HD and HD+APC groups (n = 7). HD and HD+APC groups were fed with a HD for 16 weeks. APC (25 mg/ kg) was given to the HD+APC group by orogastric gavage 5 days a week for the last 4 weeks. The effect of APC on atherosclerosis-related metabolic parameters (triglyceride, total cholesterol, HDL-cholesterol, insulin and leptin), OS [malondialdehyde, glutathione, NADPH oxidase-2, oxidized-LDL (ox-LDL) and 8-hydroxy-2-deoxyguanosine], LDL and ox-LDL uptake potential (activin receptor-like kinase-1, oxidized-LDL receptor-1), tissue inflammation (myeloperoxidase, monocyte chemoattractant protein-1, tumor necrosis factor-alpha), endothelial dysfunction (ED) (endothelial-nitric oxide synthase, inducible-nitric oxide synthase, nitric oxide), programmed cell death (terminal-deoxynucleotidyl transferase-dUTP nick end labeling, cleaved-poly ADP ribose polymerase, gasdermin-D N-terminal fragment, caspase-1), smooth muscle cell transformation (alpha-smooth muscle actin), thoracic aorta histology and ultrastructure were evaluated using different methods. Results: While APC showed an ameliorating effect on metabolic parameters, OS, inflammation, ED, programmed cell death, and ox-LDL uptake potential, it had no effect on foam cell formation and LDL uptake potential in obesity. Conclusion: Apocynin may improve the pathogenesis of endothelial dysfunction and atherosclerosis in obesity by suppressing oxidative stress-related factors involved in the early stage of atherosclerosis.