The Effect of Liraglutide on Cardiac Functions in Ovariectomized Rats

Öz

Aim: Glucagon-like peptide 1 (GLP-1) is an important incretin hormone secreted from enteroendocrine L cells. GLP-1 analogs are used for the treatment of diabetes and obesity. Ovarian hormones are well known in playing critical roles in regulating cardiovascular functions. Cardiovascular disease incidence increases in postmenopausal women. The aim of this study was to investigate the effect of administration of liraglutide, a GLP 1 analogue, on cardiac function and cardiac tissue oxidative stress in ovariectomized rats. Material and Methods: Thirty two young female Wistar albino rats were used in the study. Subjects were randomly divided into control, liraglutide-treated control, ovariectomized (OVX), and liraglutide-treated OVX groups. Ovariectomy and sham surgical procedures were performed in 2-month-old female rats. Liraglutide treatment (150μg/kg, subcutaneous, 14 days) was started five weeks after the ovariectomy operation. After measuring the heart rate and blood pressure at the end of the 14-day period, the animals were sacrificed, brown and white adipose tissue weights, and heart tissue malondialdehyde (MDA), reduced glutathione (GSH), nitrate, glycogen and ascorbic acid levels were measured. Results: While there was no difference between all groups in terms of heart rate, blood pressure was statistically significantly decreased in the liraglutide-administered groups. MDA and ascorbic acid levels did not change significantly between all groups. GSH levels were increased in the liraglutide-treated OVX group. It was found that the cardiac glycogen level was increased in the OVX group treated with OVX and liraglutide compared to the control group. Nitral levels in the heart tissue were found to be decreased with ovarectomy. Liraglutide treatment maintained nitrate levels in the heart at control levels. In addition, liraglutide administration reduced retroperitoneal fat deposition in OVX rats. Conclusion: Our results showed that GLP-1 administration was effective in reducing the increased blood pressure due to ovariectomy and maintaining the decreased GSH level in the heart tissue.. Therefore, GLP-1 analogs can be considered as potential therapeutic agents in the regulation of blood pressure in the postmenopausal period.

Anahtar Kelimeler

• GLP-1
• Ovariectomy
• Oxidative stress
• Heart

Ovariektomize Sıçanlarda Liraglutid’in Kalp Fonksiyonları Üzerine Etkisi

Öz

Amaç: Glukagon benzeri peptit-1 (GLP-1), enteroendokrin L hücrelerinden salgılanan önemli bir inkretin hormondur. GLP-1 analogları, diyabet ve obezite tedavisi için kullanılmaktadır. Ovaryan hormonların kardiyovasküler fonksiyonların düzenlenmesinde etkili rol oynadığı iyi bilinmektedir. Postmenopozal kadınlarda kardiyovasküler hastalık insidansı artar. Bu çalışmanın amacı, yumurtalıkları alınmış sıçanlarda GLP- 1 analoğu olan liraglutid uygulanmasının kardiyak fonksiyonlar ve kalp dokusu oksidatif stres üzerindeki etkisini araştırmaktır. Gereç ve Yöntemler: Çalışmada otuz iki genç dişi Wistar albino sıçan kullanıldı. Denekler rastgele kontrol, liraglutid ile tedavi edilen kontrol, yumurtalıkları alınan (OVX) ve liraglutid ile tedavi edilen OVX gruplarına ayrıldı. İki aylık dişi sıçanlarda ovariektomi ve sahte cerrahi işlemler uygulandı. Ovariektomi operasyonundan beş hafta sonra liraglutid tedavisi (150μg/kg, deri altı, 14 gün) başlandı. 14 günlük süre sonunda kalp atım hızı ve kan basıncı ölçümleri yapıldıktan sonra hayvanlar sakrifiye edildi, kahverengi ve beyaz yağ dokusu ağırlıkları ile kalp dokusu malondialdehit (MDA), indirgenmiş glutatyon (GSH), nitrat, glikojen ve askorbik asit seviyeleri ölçüldü. Bulgular: Kalp hızı açısından tüm gruplar arasında fark bulunmazken, liraglutid uygulanan gruplarda kan basıncı istatistiksel olarak anlamlı derecede azaldı. MDA ve askorbik asit seviyeleri tüm gruplar arasında önemli bir değişim gözlenmedi. GSH seviyeleri liraglutid ile tedavi edilen OVX grubunda arttı. Ovariektomi ile kalp dokusunda nitrat düzeylerinin azaldığı saptandı. Kardiyak glikojen düzeyi OVX ve liraglutid uygulanan OVX grubunda kontrol grubuna göre artmış olarak bulunmuştur. Liraglutid tedavisi kalpteki nitrat miktarını kontrol seviyelerinde korudu. Ek olarak, liraglutid uygulaması OVX sıçanlarında retroperitoneal yağ birikimini azalttı. Sonuç: Sonuçlarımız GLP-1 uygulamasının ovariektominin neden olduğu kan basıncı artışı ve kalp dokusunda azalan GSH seviyelerini korumada etkili olduğu bulunmuştur. Bu nedenle, GLP-1 analogları, postmenopozal dönemde kan basıncının düzenlenmesinde potansiyel terapötik ajan olarak kabul edilebilir.

Anahtar Kelimeler

• GLP-1
• Ovarektomi
• Oksidatif stres
• Kalp

Kaynakça

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