PİNEALEKTOMİZE EDİLMİŞ VE STREPTOZOTOSİN İLE DİYABET OLUŞTURULMUŞ RATLARDA NEFROPATİ ÜZERİNE KROSİNİN KORUYUCU ETKİLERİNİN ARAŞTIRILMASI
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2021-11
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info:eu-repo/semantics/openAccess
Özet
Diyabetes melilitus (DM) insülin hormonunun azlığı veya yokluğu ile bilinen 21. yüzyılın en büyük küresel sağlık sorunlarından biridir. 2019 yılında 20 ile 64 yaş arasında yapılan araştırmalara göre 351,7 milyon insanın DM ye sahip olduğu bu sayının 2030 da ise 417,3 milyona ulaşacağı öngörülmektedir. DM ilerleyen süreçte felç, kardiyovasküler ve böbrek hastalıkları, körlük ve alt ekstremiteler de ampütasyona varan komplikasyonlara sebep olmaktadır. Bu durum, özellikle diyabetli kişilerin %79 unun yaşadığı düşük ve orta gelirli ülkelerde, aileler ve ekonomiler üzerinde ağır bir yük oluşturmaktadır. DM sonucu görülen ciddi mikrovasküler komplikasyonlardan biri olan diyabetik nefropati, son dönemde dünya çapında artış gösteren böbrek yetmezliğinin ana nedenleri arasında yer alır ve diyabet hastalarında yaklaşık %45 gibi yüksek bir oranda görülmektedir. Kronik hiperglisemi böbrek dokusunda oksidatif strese ve inflamatuar yanıtın oluşmasına sebep olur. Bu durum podosit lezyonları, glomerüloskleroz ve azalmış glomerüler filtrasyon hızına (GFR) bağlı tubulointerstisyel fibrozis gibi böbrek histolojik yapısında değişikliklere yol açar. Bu değişiklikler kronik hipergliseminin neden olduğu reaktif oksijen türlerinin (ROS) oluşumu ile bağlantılı olup glukoz oto-oksidasyon, Fenton reaksiyonu, antioksidan kaynakların tükenmesi gibi enzimatik ve enzimatik olmayan sistemlerden kaynaklanır. Crocus sativus L. (safran) tıbbi amaçlı kullanılan 150’den fazla uçucu olan ve olmayan bileşenleri içeren aromatik bir bitkidir. Safranın biyoaktif bileşenleri arasındaki antioksidan ve radikal süpürücü özelliği olan krosin, oksidatif strese karşı koruyucu bir role sahiptir. Ayrıca anti-kanserojen, antiinflamatuar, hepatositlerin toksinlerden korunması, nörodejeneratif ve nefrotoksik bozuklukların tedavisi gibi geleneksel tıpta birçok alanda kullanılmaktadır. Çalışmamızda, deneyin ilk gününde ratlara pinealektomi işlemi uygulanarak melatonin yoksunluğu oluşturuldu. Pinealektomiyi takip eden 30. günde diyabet indüksiyonu için intraperitonal (i.p) olarak tek doz streptozotosin (STZ) enjeksiyonu yapıldı. STZ uygulamasını takiben 3. günde kuyruk kanından glukoz ölçümü yapılarak diyabet doğrulanmasının ardından 15 gün süreyle krosin tedavisi yapılan Wistar albino ratların böbrek dokusu ve serumundaki biyokimyasal parametreler ve oksidatif stres belirteçlerini ayrıca histopatolojik ve böbrek dokusunun immünohistokimyasal değerlendirmeler göz önünde bulundurularak, STZ ile kombine edilmiş krosin tedavisinin nefrotoksisite üzerindeki olası etkilerini ve STZ kaynaklı nefrotoksisite patogenezinin olası rolünü değerlendirmeyi amaçladık. Bu amaçla altmış rat altı gruba ayrıldı; (a) Kontrol; %0,9 serum fizyolojik i.p olarak aldı, (b) STZ; deneyin 30. günün sonunda periton içi 50 mg/kg STZ enjeksiyonu ile deneysel diyabet oluşturulduktan sonra 15 gün süreyle i.p olarak serum fizyolojik aldı, (c) PX; epifiz bezi pinealektomi ile alındıktan sonra 15 gün süreyle i.p olarak serum fizyolojik aldı, (d) PX+STZ; epifiz bezi pinealektomi ile alındıktan sonra deneyin 30. günün sonunda periton içi 50 mg/kg dozda STZ enjeksiyonu ile deneysel diyabet oluşturulduktan sonra 15 gün süreyle i.p olarak serum fizyolojik uygulandı, (e) PX+Krosin; epifiz bezi pinealektomi ile alındıktan sonra deneyin 30. gününün sonundan itibaren 15 gün süreyle 50 mg/kg dozda i.p olarak krosin uygulandı, (f) PX+STZ+Krosin; epifiz bezi pinealektomi ile çıkarıldıktan sonra 30. günün sonunda periton içi 50 mg/kg dozda STZ enjeksiyonu ile deneysel diyabet modeli oluşturulduktan sonra 15 gün süreyle 50 mg/kg dozda i.p olarak krosin uygulandı. Çalışmamıza göre STZ ile indüklenen pinealektomize diyabetik ratlarda böbrek fonksiyon parametrelerinde (BUN ve Kreatinin) önemli artışlar görüldü. Dahası STZ oksidatif stres parametrelerinde (malondialdehit, toplam oksidan seviyesi ve oksidatif stres indeksi) önemli artışlara ve ayrıca antioksidan savunma sistemlerinden (redükte glutatyon, süperoksit dismutaz, katalaz ve toplam antioksidan seviyesi) azalmaya neden oldu. Çalışmamızda yine pinealektomize ve STZ ile diyabet yapılan ratlarda krosin tedavisi edildiğinde, krosin ile tedavi edilmeyenlere kıyasla böbrek fonksiyon parametrelerini ve biyokimyasal parametreleri önemli ölçüde iyileştirdiğini göstermiştir. Histopatolojik ve immünohistokimyasal değerlendirmeler de sonuçlarımızı desteklenmiştir. Sonuç olarak, krosinin diyabetik nefropati üzerindeki koruyucu etkileri, güçlü antioksidan özellikleri, doku antioksidan durumunu iyileştirme yeteneği ve inflamatuar yolları önleme yeteneği ile ilişkili olabileceğini ortaya koymaktadır.
Diabetes melilitus (DM) is known for the lack or absence of insulin and is one of the most important global health problems of the 21st century. In a study conducted in 2019, it was reported that 351.7 million people between the ages of 20 and 64 have DM, and this number will reach 417.3 million in 2030. Uncontrolled DM causes complications including stroke, cardiovascular and kidney diseases, blindness, and amputation of the legs. DM imposes enormous costs on families and economies, especially in low- and middle-income countries where the proportion of people with diabetes is 79%. Renal failure, one of the most important complications of DM, is seen in approximately 45% of diabetic patients and DM causes diabetic nephropathy as a result of microvascular complications. Chronic hyperglycemia causes oxidative stress and inflammatory response in kidney tissue. This leads to changes in kidney histological structure such as podocyte lesions, glomerulosclerosis and tubulointerstitial fibrosis due to decreased glomerular filtration rate (GFR). These changes are associated with the formation of reactive oxygen species (ROS) caused by chronic hyperglycemia and are produced by enzymatic and non-enzymatic systems such as glucose auto-oxidation, Fenton reaction, and depletion of antioxidant sources. Crocus sativus L. (saffron) is an aromatic plant used for medicinal purposes and has more than 150 volatile and non-volatile components. Crocin, one of the main components of saffron, has a protective role against oxidative stress with its antioxidant and radical scavenging properties. In addition, it is used in many diseases in traditional medicine due to its anti-carcinogenic, anti-inflammatory, hepatoprotective, neuroprotective and nephroprotective properties. In our study, melatonin deprivation was created by removing the pineal glands of the rats on the first day of the experiment. On the 30th day following pinealectomy, a single intraperitoneal (i.p) injection of streptozotocin (STZ) was performed for diabetes induction. On the 3rd day following the STZ application, diabetes was confirmed by measuring glucose from the tail blood, and then crocin treatment was applied for 15 days. We aimed to evaluate the possible effects of crocin therapy combined with STZ on nephrotoxicity and its possible role in the pathogenesis of STZ-induced nephrotoxicity by measuring biochemical parameters and oxidative stress markers in kidney tissue and serum of Wistar albino rats, as well as histopathological and immunohistochemical evaluations of kidney tissue. For this purpose, sixty rats were divided into six groups; (a) Control; 0.9% saline received as ip, (b) STZ; received saline as ip for 15 days after experimental diabetes was established by intraperitoneal injection of 50 mg/kg STZ at the end of the 30th day of the experiment, ( c) PX; Pineal gland was removed by pinealectomy and received saline as ip for 15 days, (d) PX+STZ; Pineal gland was removed by pinealectomy, experimental diabetes was induced by intraperitoneal injection of 50 mg/kg STZ on the 30th day of the experiment. and saline was applied as ip for 15 days, (e) PX+ Crocin; After the pineal gland was removed by pinealectomy, 50 mg/kg crocin was applied as ip for 15 days, (f) PX+STZ+Crocin; Pineal gland was taken with pinealectomy on the 30th day of the experiment, an experimental diabetes model was created by intraperitoneal injection of 50 mg/kg STZ and crocin was administered at a dose of 50 mg/kg ip for 15 days. In our study, significant increases in renal function parameters (BUN and creatinine) were observed in pinealectomized diabetic rats induced by STZ. Moreover, STZ caused significant increases in oxidative stress parameters (malondialdehyde, total oxidant status and oxidative stress index) as well as a decrease in antioxidant defense systems [reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS)]. On the other hand, treatment of pinealectomized diabetic rats with crocin significantly improved renal function parameters and biochemical parameters compared to untreated pinealectomized diabetic rats. Histopathological and immunohistochemical evaluations also supported our results. In conclusion, the protective effects of crocin on diabetic nephropathy may be related to its potent antioxidant properties, ability to improve tissue antioxidant status, and ability to inhibit inflammatory pathways."
Diabetes melilitus (DM) is known for the lack or absence of insulin and is one of the most important global health problems of the 21st century. In a study conducted in 2019, it was reported that 351.7 million people between the ages of 20 and 64 have DM, and this number will reach 417.3 million in 2030. Uncontrolled DM causes complications including stroke, cardiovascular and kidney diseases, blindness, and amputation of the legs. DM imposes enormous costs on families and economies, especially in low- and middle-income countries where the proportion of people with diabetes is 79%. Renal failure, one of the most important complications of DM, is seen in approximately 45% of diabetic patients and DM causes diabetic nephropathy as a result of microvascular complications. Chronic hyperglycemia causes oxidative stress and inflammatory response in kidney tissue. This leads to changes in kidney histological structure such as podocyte lesions, glomerulosclerosis and tubulointerstitial fibrosis due to decreased glomerular filtration rate (GFR). These changes are associated with the formation of reactive oxygen species (ROS) caused by chronic hyperglycemia and are produced by enzymatic and non-enzymatic systems such as glucose auto-oxidation, Fenton reaction, and depletion of antioxidant sources. Crocus sativus L. (saffron) is an aromatic plant used for medicinal purposes and has more than 150 volatile and non-volatile components. Crocin, one of the main components of saffron, has a protective role against oxidative stress with its antioxidant and radical scavenging properties. In addition, it is used in many diseases in traditional medicine due to its anti-carcinogenic, anti-inflammatory, hepatoprotective, neuroprotective and nephroprotective properties. In our study, melatonin deprivation was created by removing the pineal glands of the rats on the first day of the experiment. On the 30th day following pinealectomy, a single intraperitoneal (i.p) injection of streptozotocin (STZ) was performed for diabetes induction. On the 3rd day following the STZ application, diabetes was confirmed by measuring glucose from the tail blood, and then crocin treatment was applied for 15 days. We aimed to evaluate the possible effects of crocin therapy combined with STZ on nephrotoxicity and its possible role in the pathogenesis of STZ-induced nephrotoxicity by measuring biochemical parameters and oxidative stress markers in kidney tissue and serum of Wistar albino rats, as well as histopathological and immunohistochemical evaluations of kidney tissue. For this purpose, sixty rats were divided into six groups; (a) Control; 0.9% saline received as ip, (b) STZ; received saline as ip for 15 days after experimental diabetes was established by intraperitoneal injection of 50 mg/kg STZ at the end of the 30th day of the experiment, ( c) PX; Pineal gland was removed by pinealectomy and received saline as ip for 15 days, (d) PX+STZ; Pineal gland was removed by pinealectomy, experimental diabetes was induced by intraperitoneal injection of 50 mg/kg STZ on the 30th day of the experiment. and saline was applied as ip for 15 days, (e) PX+ Crocin; After the pineal gland was removed by pinealectomy, 50 mg/kg crocin was applied as ip for 15 days, (f) PX+STZ+Crocin; Pineal gland was taken with pinealectomy on the 30th day of the experiment, an experimental diabetes model was created by intraperitoneal injection of 50 mg/kg STZ and crocin was administered at a dose of 50 mg/kg ip for 15 days. In our study, significant increases in renal function parameters (BUN and creatinine) were observed in pinealectomized diabetic rats induced by STZ. Moreover, STZ caused significant increases in oxidative stress parameters (malondialdehyde, total oxidant status and oxidative stress index) as well as a decrease in antioxidant defense systems [reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS)]. On the other hand, treatment of pinealectomized diabetic rats with crocin significantly improved renal function parameters and biochemical parameters compared to untreated pinealectomized diabetic rats. Histopathological and immunohistochemical evaluations also supported our results. In conclusion, the protective effects of crocin on diabetic nephropathy may be related to its potent antioxidant properties, ability to improve tissue antioxidant status, and ability to inhibit inflammatory pathways."
Açıklama
Anahtar Kelimeler
Pinealektomi, Krosin, Böbrek Hasarı, Tümör Büyüme Faktörü, Streptozotosin, Oksidatif Stres, Pinealectomy, Crocin, Kidney Damage, Tumor Growth Factor, Streptozotocin, Oxidative Stress