Ferropitozun yüksek fruktozlu beslenme ve bağlı böbrek işlev bozukluğundaki rolü
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Tarih
2022
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Yayıncı
Trakya Üniversitesi Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Çalışmamızda yüksek fruktozlu beslenmeye bağlı oluşan böbrek hasarında ferropitozun rolünü ve yüksek fruktozlu beslenmenin böbrek fonksiyon ve histolojisindeki değişimini zamana bağlı olarak incelemeyi amaçladık. Etik onay alındıktan sonra 4 grupta toplam 34 adet Spraque-Dawley erkek sıçan kullanıldı. Deney süresince kontrol grubuna çeşme suyu, diğer gruplara %20 fruktoz içeren çeşme suyu verildi. Kontrol grubu 1 hafta, F4 grubu 4 hafta, F8 grubu 8 hafta ve F12 grubu 12 hafta takip edildi. Deney sürelerinin son gününde sıçanlar metabolik kafese alınarak 24 saatlik idrarları toplandı. Ardından anestezi altında kan örnekleri ve böbrekleri alındı. Serum numunelerinde üre, kreatinin, ürik asit, kalsiyum ve potasyum düzeyleri, idrar numunelerinde kreatinin klirensi ve FeNa düzeyleri, böbrek dokusunda glutatyon (GSH), malondialdehit MDA, glutatyon peroksidaz 4 (GPX4), açil-coa sentetaz uzun zincirli aile üyesi 4 (ACSL4), transferrin reseptör 1 (TFR1), doku demir düzeyleri, histopatolojik değişiklikler ve immünohistokimyasal GPX4 ve ACSL4 boyanma düzeyleri incelendi. Çalışmamızda 12 hafta fruktozla beslenen grupta tüm gruplara göre serum kreatinin seviyesinde anlamlı artış gözlenirken serum üre seviyesinde kontrol grubuna göre tüm gruplarda anlamlı düşüş gözlendi. Serum kalsiyum düzeyinde F8 grubunda kontrole göre anlamlı azalma görüldü. Kreatinin klirensi / vücut ağırlığı seviyelerinde F12 grubunda, FeNa seviyelerinde ise kontrol grubuna göre tüm gruplarda anlamlı azalma gözlendi. 24 saatlik idrar hacminde F4 ve F12 gruplarında kontrole göre anlamlı artış, F8 grubunda F4 grubuna göre anlamlı azalma gözlendi. Böbrek dokusunda GSH düzeylerinde F8 ve F12 gruplarında kontrole göre anlamlı azalma görülürken MDA seviyelerinde gruplar arası farklılık gözlenmedi. Ferropitoz belirteçlerinden GPX4 seviyelerinde kontrole göre tüm gruplarda anlamlı azalma, diğer ferropitoz belirteçlerinde anlamlı farklılık gözlenmedi. Histolojik olarak renal hasar skoru ve glomerüler çap F8 ve F12 gruplarında anlamlı yüksekti. Tüm bu sonuçlar toplu olarak değerlendirildiğinde fruktozdan zengin beslenmenin böbrek fonksiyon ve histolojisini olumsuz etkilediği ve fruktozdan zengin beslenme süresinin uzamasının bu etkileri arttırdığı görüldü. Yüksek fruktoz alımına bağlı olumsuz etkilerde ferropitozun rolünü incelediğimizde bulgularımızın çelişkili olması sebebiyle yüksek fruktozlu beslenmeye bağlı oluşan hasarda ferropitozun rolü konusunda net bir sonuca ulaşılamadı. Uygulanan modelde fruktoz dozunda çeşitlilik ve çalışma süresi artırılarak ek çalışmalar yapılmasının uygun olacağı düşünüldü.
In our study, we aimed to examine the role of ferroptosis in kidney damage caused by high fructose nutrition and the change of high fructose nutrition in kidney function and histology over time. After ethical approval, a total of 34 Spraque-Dawley male rats were used in 4 groups. During the experiment, tap water was given to the control group and tap water containing 20% fructose was given to the other groups. The control group was followed for 1 week, the F4 group for 4 weeks, the F8 group for 8 weeks, and the F12 group for 12 weeks. On the last day of the experimental period, the rats were taken into the metabolic cage and their 24-hour urine was collected. Then, blood samples and kidneys were taken under anesthesia. Urea, creatinine, uric acid, calcium and potassium levels in serum samples, creatinine clearance and FeNa levels in urine samples, glutathione (GSH), malondialdehyde (MDA), malondialdehyde (GPX4), acyl-coa synthetase long chain family member 4 (ACSL4), transferrin receptor 1 (TFR1), and tissue iron levels in kidney tissue samples, histopathological changes and immunohistochemical GPX4 and ACSL4 staining levels in kidney tissue were examined. In our study, a significant increase was observed in serum creatinine level in the group fed with fructose for 12 weeks compared to all groups, while a significant decrease was observed in serum urea level in all groups compared to the control group. There was a significant decrease in serum calcium level in the F8 group compared to the control. A significant decrease was observed in creatinine clearance / body weight levels in the F12 group, and in FeNa levels in all groups compared to the control group. A significant increase in 24-hour urine volume was observed in the F4 and F12 groups compared to the control group, and a significant decrease was observed in the F8 group compared to the F4 group. There was a significant decrease in GSH levels in the kidney tissue in the F8 and F12 groups compared to the control, but no difference was observed between the groups in MDA levels. A significant decrease was observed in GPX4 levels, one of the ferroptosis markers, in all groups compared to the control, and no significant difference was observed in other ferroptosis markers. Histologically, renal injury score and glomerular diameter were significantly higher in the F8 and F12 groups. When all these results were evaluated collectively, it was seen that fructose-rich diet negatively affected kidney function and histology, and prolonged fructose-rich diet increased these effects. When we examined the role of ferroptosis in the negative effects of high fructose intake, we could not reach a clear conclusion about the role of ferroptosis in the damage caused by high fructose nutrition, since our findings were contradictory. In the applied model, it was thought that it would be appropriate to carry out additional studies by increasing the diversity and working time in fructose dose.
In our study, we aimed to examine the role of ferroptosis in kidney damage caused by high fructose nutrition and the change of high fructose nutrition in kidney function and histology over time. After ethical approval, a total of 34 Spraque-Dawley male rats were used in 4 groups. During the experiment, tap water was given to the control group and tap water containing 20% fructose was given to the other groups. The control group was followed for 1 week, the F4 group for 4 weeks, the F8 group for 8 weeks, and the F12 group for 12 weeks. On the last day of the experimental period, the rats were taken into the metabolic cage and their 24-hour urine was collected. Then, blood samples and kidneys were taken under anesthesia. Urea, creatinine, uric acid, calcium and potassium levels in serum samples, creatinine clearance and FeNa levels in urine samples, glutathione (GSH), malondialdehyde (MDA), malondialdehyde (GPX4), acyl-coa synthetase long chain family member 4 (ACSL4), transferrin receptor 1 (TFR1), and tissue iron levels in kidney tissue samples, histopathological changes and immunohistochemical GPX4 and ACSL4 staining levels in kidney tissue were examined. In our study, a significant increase was observed in serum creatinine level in the group fed with fructose for 12 weeks compared to all groups, while a significant decrease was observed in serum urea level in all groups compared to the control group. There was a significant decrease in serum calcium level in the F8 group compared to the control. A significant decrease was observed in creatinine clearance / body weight levels in the F12 group, and in FeNa levels in all groups compared to the control group. A significant increase in 24-hour urine volume was observed in the F4 and F12 groups compared to the control group, and a significant decrease was observed in the F8 group compared to the F4 group. There was a significant decrease in GSH levels in the kidney tissue in the F8 and F12 groups compared to the control, but no difference was observed between the groups in MDA levels. A significant decrease was observed in GPX4 levels, one of the ferroptosis markers, in all groups compared to the control, and no significant difference was observed in other ferroptosis markers. Histologically, renal injury score and glomerular diameter were significantly higher in the F8 and F12 groups. When all these results were evaluated collectively, it was seen that fructose-rich diet negatively affected kidney function and histology, and prolonged fructose-rich diet increased these effects. When we examined the role of ferroptosis in the negative effects of high fructose intake, we could not reach a clear conclusion about the role of ferroptosis in the damage caused by high fructose nutrition, since our findings were contradictory. In the applied model, it was thought that it would be appropriate to carry out additional studies by increasing the diversity and working time in fructose dose.
Açıklama
Anahtar Kelimeler
Ferropitoz, Fruktozlu, Beslenme, Oksidatif stres, Ferroptosis, Fructose, Diet, Oxidative stress
