Protective Effect of Silymarine in Rat Model Experimentally Formed Overian Hyperstimulation Syndrome
Abstract
over hiperstimülasyon sendromunun (OHSS) yönetimi ve öngörülmesinde ilerlemeler sağlanmış olsa da, OHSS'yi önlemek henüz mümkün değildir. Anjiyogenezisin, OHSS etyolojisinde yer aldığı gösterilmiştir. Silimarin geniş spektrumlu etkiye sahip bitkisel kaynaklı bir bileşendir. Bu çalışma da ki amacımız silimarinin OHSS'nin gelişme riskine karşı korumada kullanılıp kullanılamayacağını araştırmayı amaçladık. Çalışmamızda 22 günlük, 32 adet Wistar Albino cinsi dişi rat kullanılarak OHSS modeli oluşturuldu. Bunun için ratlar 15 günlük iken alındı 7 gün labaratovar şartlarında 22 günlük ve ortalama ağırlıkları 40-50 gr olan kadar standart diet ve sınırsız su ile beslendi ve 12 saat aydınlık, 12 saat karanlık olacak şekilde ve uygun nem ortamında bakıldı. Ratlar her grupta 8 tane olacak şekilde rastgele 4 guruba ayrıldı. Grup 1: Kontrol (n=8) Grubu; Postnatal 22-26 günler arası: %0,9 NaCl intraperitoneal (i.p.) Grup 2: OHSS Grubu (n=8); Postnatal 22. günden itibaren 4 gün boyunca 10 IU PMSG s.c. ve postnatal 26. gün: 30 IU hCG s.c. Grup 3: silymarin uygulanmış OHSS Grubu (n=8) (OHSS+S); Postnatal 22. günden itibaren 4 gün boyunca 10 IU PMSG s.c. ve postnatal 26. Gün 30 IU hCG s.c., hCG'den 30 dk önce ve 8 saat sonra 50mg/kg dan 2 doz silymarin oral gavaj şeklinde verildi. Grup 4: Silymarin (n=8) Grubu; Postnatal 26 günde 50mg/kg 8 saat ara ile 2 doz olarak oral gavaj şeklinde verildi. Peritoneal sıvı ve serum örnekleri 900 X g' de 12 dakika santrifuj edildildi. VEGF, TNF-α, ANGPT1, ANGPT2 ölçümleri kantitatif olarak 'Enzymelinked immunosorbent assay' (ELISA) kiti kullanılarak ölçüldü. OHSS grubu serum VEGF-A ve ANGPT-1 seviyeleri kontrol ve silimarin gruplarından anlamlı olarak yüksekken (p<0.05), ANGPT-2 seviyesi anlamlı olarak düşüktü (p<0.05). OHSS +S grubu, OHSS grubu ile karşılaştırıldığında VEGF-A ve ANGPT-1 seviyeleri düşük olmasına rağmen anlamlı değildi (p>0.05). ANGPT-2 seviyesi OHSS grubu ile karşılaştırıldığında OHSS-S grubunda anlamlı olarak yüksek bulunmuştur (p<0.05). TNF-α seviyeleri gruplar arasında farklı değildi. OHSS'nin gelişmesinde önemli aracılar olabilen VEGF-A ve ANGPT-1 seviyesinde düşmeye neden olarak ve ANGPT-2 seviyesinde artmaya neden olduğundan OHSS gelişmesini önlemede kullanıbileceğini düşünmekteyiz. Anahtar Kelimeler: OHSS, Silimarin, VEGF-A, ANGPT
Although advances have been made in the management and prediction of ovarian hyperstimulation syndrome (OHSS), it is not yet possible to prevent OHSS. Angiogenesis has been shown to be involved in the etiology of OHSS. Silymarin is a plant-derived ingredient with a broad-spectrum effect. Our aim in this study was to investigate whether silymarin can be used to protect against the risk of developing OHSS. In the study, an OHSS model was created using 32 Wistar Albino female rats aged 22 days. For this, rats were taken when they were 15 days old, and they were fed with standard diet and unlimited water for 7 days, 22 days old and average weight of 40-50 g under laboratory conditions, and they were kept in 12 hours of light, 12 hours of darkness and in a suitable humidity environment. Rats were randomly divided into 4 groups with 8 in each group. Group 1: Control (n=8) Group; Postnatal 22-26 days: 0.9% NaCl intraperitoneally (i.p.) Group 2: OHSS Group (n=8); From postnatal day 22, 10 IU PMSG s.c. for 4 days. and postnatal day 26: 30 IU hCG s.c. Group 3: OHSS Group treated with silymarin (n=8); From postnatal day 22, 10 IU PMSG s.c. for 4 days. and postnatal Day 26 30 IU hCG s.c. 2 doses of 50mg/kg silymarin were given as oral gavage, 30 minutes before and 8 hours after hCG. Group 4: Silymarin (n=8) Group; In the postnatal 26 days, 50mg/kg was given as 2 doses with 8 hour intervals in the form of oral gavage. Peritoneal fluid and serum samples were centrifuged at 900 X g for 12 minutes. VEGF, TNF, ANG1, ANG2 measurements were quantitatively measured using the 'Enzyme-linked immunosorbent assay' (ELISA) kit. Serum VEGF-A and ANGPT-1 levels in the OHSS group were significantly higher than in the control and silymarin groups (p<0.05), while ANGPT-2 levels were significantly lower (p<0.05). Although VEGF-A and ANGPT-1 levels were low in the OHSS +S group compared to the OHSS group, they were not significant (p>0.05). When ANGPT-2 level was compared with the OHSS group, it was found to be significantly higher in the OHSS-S group (p<0.05).TNF-α levels were not different between groups. We think that it can be used to prevent the development of OHSS by causing a decrease in VEGF-A and ANGPT-1 levels, which can be important mediators in the development of OHSS, and an increase in ANGPT-2 levels. Key Words: OHSS, Silymarin, VEGF-A, ANGPT
Although advances have been made in the management and prediction of ovarian hyperstimulation syndrome (OHSS), it is not yet possible to prevent OHSS. Angiogenesis has been shown to be involved in the etiology of OHSS. Silymarin is a plant-derived ingredient with a broad-spectrum effect. Our aim in this study was to investigate whether silymarin can be used to protect against the risk of developing OHSS. In the study, an OHSS model was created using 32 Wistar Albino female rats aged 22 days. For this, rats were taken when they were 15 days old, and they were fed with standard diet and unlimited water for 7 days, 22 days old and average weight of 40-50 g under laboratory conditions, and they were kept in 12 hours of light, 12 hours of darkness and in a suitable humidity environment. Rats were randomly divided into 4 groups with 8 in each group. Group 1: Control (n=8) Group; Postnatal 22-26 days: 0.9% NaCl intraperitoneally (i.p.) Group 2: OHSS Group (n=8); From postnatal day 22, 10 IU PMSG s.c. for 4 days. and postnatal day 26: 30 IU hCG s.c. Group 3: OHSS Group treated with silymarin (n=8); From postnatal day 22, 10 IU PMSG s.c. for 4 days. and postnatal Day 26 30 IU hCG s.c. 2 doses of 50mg/kg silymarin were given as oral gavage, 30 minutes before and 8 hours after hCG. Group 4: Silymarin (n=8) Group; In the postnatal 26 days, 50mg/kg was given as 2 doses with 8 hour intervals in the form of oral gavage. Peritoneal fluid and serum samples were centrifuged at 900 X g for 12 minutes. VEGF, TNF, ANG1, ANG2 measurements were quantitatively measured using the 'Enzyme-linked immunosorbent assay' (ELISA) kit. Serum VEGF-A and ANGPT-1 levels in the OHSS group were significantly higher than in the control and silymarin groups (p<0.05), while ANGPT-2 levels were significantly lower (p<0.05). Although VEGF-A and ANGPT-1 levels were low in the OHSS +S group compared to the OHSS group, they were not significant (p>0.05). When ANGPT-2 level was compared with the OHSS group, it was found to be significantly higher in the OHSS-S group (p<0.05).TNF-α levels were not different between groups. We think that it can be used to prevent the development of OHSS by causing a decrease in VEGF-A and ANGPT-1 levels, which can be important mediators in the development of OHSS, and an increase in ANGPT-2 levels. Key Words: OHSS, Silymarin, VEGF-A, ANGPT
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Kadın Hastalıkları ve Doğum, Anjiopoietinler, Hayvan deneyleri, Over hiperstimülasyon sendromu, Silimarin, Sıçanlar, Vasküler endotel büyüme faktörleri, Obstetrics and Gynecology, Angiopoietins, Animal experimentation, Ovarian hyperstimulation syndrome, Silymarin, Rats, Vascular endothelial growth factors
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