SIÇANLARDA METOTREKSAT KAYNAKLI BÖBREK TOKSİSİTESİ ÜZERİNE MORİNİN KORUYUCU ETKİSİ
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2021-09
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info:eu-repo/semantics/openAccess
Özet
Yüksek Lisans Tezi SIÇANLARDA METOTREKSAT KAYNAKLI BÖBREK TOKSİSİTESİ ÜZERİNE MORİNİN KORUYUCU ETKİSİ Şeyda SEÇGİN Karabük Üniversitesi Lisansüstü Eğitim Enstitüsü Tıbbi Biyokimya Anabilim Dalı Tez Danışmanı: Prof. Dr. Tahir KAHRAMAN Eylül 2021, 59 sayfa Antimetabolit grubu ilaçların geniş kullanım alanları olmasına rağmen birçok yan etkisi de mevcuttur. Meydana gelen bu yan etkileri yok etmede bitkisel kökenli ürünlerin (özellikle flavonoidler) kullanımı birçok biyokimyasal ve farmakolojik yararlanımından dolayı oldukça önem taşımaktadır. Bu çalışmanın amacı Morin (3, 5, 7, 2 ?, 4?-pentahidroksiflavon, MOR) flavonoidinin sıçanlarda Metotreksat (MTX) antimetaboliti kaynaklı böbrek toksisitesinde antioksidan, antienflamatuar ve antiapoptotik etkileri araştırmak için yapılmıştır. Bu çalışmada 32 deney hayvanı her bir grup 8 sıçandan oluşacak şekilde 4 gruba ayrıldı. Grup 1 (Kontrol), Grup 2 (MOR), Grup 3 (MTX), Grup 4 (MTX+MOR) şeklinde gruplar oluşturulup MTX 20 mg/kg intraperitonel tek doz, MOR ise 100 mg/kg dozunda intragastrik yolla 10 gün süre ile uygulandı. Oksidatif stres belirteçleri olan malondialdehid (MDA), Total Oksidan Seviyesi (TOS) değerlerinde MTX grubuna göre kontrol, MTX+MOR ve MOR grupları arasında anlamlı bir artış oldu (p<0.05). Total Oksidan Seviyesi (TOS) değerlerinde ise MTX+MOR grubuna göre MTX grubunda anlamlı bir artış oldu (p<0.05). Antioksidan kapasite değerlendirilmesinde Total Antioksidan Seviyesi (TAS), glutatyon (GSH), Oksidatif Stres İndeksi (OSİ) değerlerinde MTX+MOR grubuna göre MOR grupları arasında anlamlı bir azalış oldu (p<0.05). Oluşturulan böbrek toksisinde böbrek fonksiyon değerlerinin analizi için serumda üre (p>0.05), kreatinin (p>0.05), ürik asit (p<0.05) ve total protein (p<0.05) değerlerine bakıldı. Özellikle MTX grubunda tüm değerlerde artış vardı fakat sadece ürik asitte anlamlı bir artışın olduğu bulundu. Ayrıca MTX+MOR grubunda ise bu değerlerin MOR ile düzeltilebildiği tespit edildi. Böbrek dokusunun histopatolojik değerlendirilmesinde MOR ve Kontrol grubunda normal histopatolojik bulgulara rastlandı. MTX, MTX+MOR gruplarında tübülller intersitisyel alanlar, glomerüler yumakta; enflamasyon, fibrozis, atrofi, dejenerasyon ve nekroz gibi patolojik bulgulara rastlandı. Fakat bu patolojilerin MTX+MOR grubunda MTX grubuna göre anlamlı azalışın olduğu bulundu (p<0.05). Sonuç olarak MTX’in böbrek dokusunda oksidatif stres, enflamasyon ve apoptoz gibi birçok etkisinin dokudaki biyokimyasal ve histopatolojik bulgular sonucu varolduğu görüldü. MOR’un ise toksik etkisinin oldukça az olması avantajı ile MTX’in sebep olduğu toksikasyonu ciddi oranda azalttığı görüldü, benzer ve destekleyici çalışmalarla mekanizmaların daha da aydınlatarak katkı da sağlayacağı görüşüne varıldı.
M. Sc. Thesis PROTECTIVE EFFECT OF MORIN IN METHOTREXAT INDUCED RENAL TOXICITY IN RATS Şeyda SEÇGİN Karabük University Institute of Graduate Programs Department of Medical Biochemistry Thesis Advisor: Prof. Dr. Tahir KAHRAMAN September 2021, 59 pages Antimetabolite is for widespread use in the field of education. My biological flavonoids are used to benefit from these tools. This purpose was made for investigations of Morine (3, 5, 7, 2?, 4?-pentahydroxyflavone, MOR) flavonoid from Methotrexate (MTX) antimetabolites, inflammation in the body, and antiapoptotic treatments in mice. In this study, 32 experimental animals were divided into 4 groups, each group consisting of 8 rats. Groups as Group 1 (Control), Group 2 (MOR), Group 3 (MTX), Group 4 (MTX+MOR) were formed and MTX was administered at a dose of 20 mg/kg intraperitoneally as a single dose, and MOR at a dose of 100 mg/kg intragastrically for 10 days. Done. There was a significant increase in malondialdehyde (MDA), Total Oxidant Status (TOS) values, which are oxidative stress markers, between the control, MTX+MOR and MOR groups compared to the MTX group (p<0.05). There was a significant increase in Total Oxidant Status (TOS) values in the MTX group compared to the MTX+MOR group (p<0.05). In the evaluation of antioxidant capacity, there was a significant decrease in Total Antioxidant Status (TAS), glutathione (GSH), Oxidative Stress Index (OSI) values between MOR groups compared to MTX+MOR group (p<0.05). Serum urea (p>0.05), creatinine (p>0.05), uric acid (p<0.05) and total protein (p<0.05) values were measured for the analysis of kidney function values in the generated kidney toxicity. There was an increase in all values, especially in the MTX group, but only a significant increase in uric acid was found. In addition, it was determined that these values could be corrected with MOR in the MTX+MOR group. In the histopathological evaluation of the kidney tissue, normal histopathological findings were found in the MOR and Control groups. In MTX, MTX+MOR groups, tubular interstitial areas were in the glomerular tuft; Pathological findings such as inflammation, fibrosis, atrophy, degeneration and necrosis were encountered. However, these pathologies were found to be significantly decreased in the MTX+MOR group compared to the MTX group (p<0.05). As a result, it was seen that many effects of MTX in kidney tissue such as oxidative stress, inflammation and apoptosis were present as a result of biochemical and histopathological findings in the tissue. MOR, on the other hand, has the advantage of having a very low toxic effect, and it has been observed that it significantly reduces the toxicity caused by MTX, and it has been concluded that similar and supportive studies will contribute by further illuminating the mechanisms."
M. Sc. Thesis PROTECTIVE EFFECT OF MORIN IN METHOTREXAT INDUCED RENAL TOXICITY IN RATS Şeyda SEÇGİN Karabük University Institute of Graduate Programs Department of Medical Biochemistry Thesis Advisor: Prof. Dr. Tahir KAHRAMAN September 2021, 59 pages Antimetabolite is for widespread use in the field of education. My biological flavonoids are used to benefit from these tools. This purpose was made for investigations of Morine (3, 5, 7, 2?, 4?-pentahydroxyflavone, MOR) flavonoid from Methotrexate (MTX) antimetabolites, inflammation in the body, and antiapoptotic treatments in mice. In this study, 32 experimental animals were divided into 4 groups, each group consisting of 8 rats. Groups as Group 1 (Control), Group 2 (MOR), Group 3 (MTX), Group 4 (MTX+MOR) were formed and MTX was administered at a dose of 20 mg/kg intraperitoneally as a single dose, and MOR at a dose of 100 mg/kg intragastrically for 10 days. Done. There was a significant increase in malondialdehyde (MDA), Total Oxidant Status (TOS) values, which are oxidative stress markers, between the control, MTX+MOR and MOR groups compared to the MTX group (p<0.05). There was a significant increase in Total Oxidant Status (TOS) values in the MTX group compared to the MTX+MOR group (p<0.05). In the evaluation of antioxidant capacity, there was a significant decrease in Total Antioxidant Status (TAS), glutathione (GSH), Oxidative Stress Index (OSI) values between MOR groups compared to MTX+MOR group (p<0.05). Serum urea (p>0.05), creatinine (p>0.05), uric acid (p<0.05) and total protein (p<0.05) values were measured for the analysis of kidney function values in the generated kidney toxicity. There was an increase in all values, especially in the MTX group, but only a significant increase in uric acid was found. In addition, it was determined that these values could be corrected with MOR in the MTX+MOR group. In the histopathological evaluation of the kidney tissue, normal histopathological findings were found in the MOR and Control groups. In MTX, MTX+MOR groups, tubular interstitial areas were in the glomerular tuft; Pathological findings such as inflammation, fibrosis, atrophy, degeneration and necrosis were encountered. However, these pathologies were found to be significantly decreased in the MTX+MOR group compared to the MTX group (p<0.05). As a result, it was seen that many effects of MTX in kidney tissue such as oxidative stress, inflammation and apoptosis were present as a result of biochemical and histopathological findings in the tissue. MOR, on the other hand, has the advantage of having a very low toxic effect, and it has been observed that it significantly reduces the toxicity caused by MTX, and it has been concluded that similar and supportive studies will contribute by further illuminating the mechanisms."
Açıklama
Anahtar Kelimeler
Metotreksat, Morin, Oksidatif stres, Toksisite, Böbrek dokusu., Methotrexate, Morin, Oxidative stress, Toxicity, Kidney tissue.
