The role of asymmetrical dimethylarginine in the rat sepsis model
İbrahim Uygun 1, Mustafa Deniz 2, Özlem Unay Demirel 3, Halil Tuğtepe 4, Serdar Hilmi İskit 5, Türkan Yurdun 6, Serpil Bilsel 7, Tolga Emrullah Dağlı 4
1Dicle Üniversitesi Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı ve Çocuk Ürolojisi Bilim Dalı, Diyarbakır
2Çanakkale Onsekiz Mart Üniversitesi Tıp Fakültesi, Fizyoloji Anabilim Dalı, Çanakkale
3Özel Medical Park Göztepe Hastanesi, Biyokimya Bölümü, İstanbul
4Marmara Üniversitesi Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı ve Çocuk Ürolojisi Bilim Dalı, İstanbul
5Çukurova Üniversitesi Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, Adana
6Marmara Üniversitesi Eczacılık Fakültesi, Farmasötik Toksikoloji Anabilim Dalı, İstanbul
7Marmara Üniversitesi Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı, İstanbul
Keywords: Asymmetrical dimethylarginine, sepsis, rat
Abstract
Aim: Asymmetrical dimethylarginine (ADMA) is a potent endogenous inhibitor of nitric oxide (NO) synthase enzymes and a physiological modulator of NO biosynthesis. In this article elevation of plasma ADMA levels in critically ill patients with multiple organ dysfunction syndrome (MODS) which is an independent risk factor in intensive care unit mortality has been emphasized. In a few recent studies attempting to explain relationship between ADMAinflammation, conflicting results have been reported about increasing or decreasing plasma ADMA levels in sepsis which is an earlier stage of MODS. We aimed to investigate the role of ADMA and L-arginine (L-Arg) during the earlier hyperdynamic, and normotensive stage of sepsis in the rat sepsis model.
Material and Methods: Male Sprague-Dawley rats were grouped as sham (n=8) and sepsis (n=8). Sepsis was induced by the cecal ligation and perforation model. Twenty four hours after the induction of sepsis, rats were monitored and their hemodynamic parameters were measured. Then rats were sacrificed and samples were taken for measurements of biochemistry parameters and plasma levels of ADMA and L-Arg. ADMA and L-Arg were measured simultaneously by high-performance liquid chromatography.
Results: In all of rats of the sepsis group, severe peritonitis and hyperdynamic normotansive early sepsis were induced. Median plasma ADMA concentration was 5.33 µM in the sham (n=6), whereas in the sepsis group (n=7) it was significantly higher (10.24 µM) (p<0.05) and in addition, between mean arterial blood pressure and plasma ADMA levels in the septic rats a positive correlation was demonstrated (r=0.77, p<0.05). Other measuremets were not significant between two groups.
Conclusion: In the hyperdynamic normotansive early sepsis, plasma ADMA levels are elevated. Plasma ADMA concentration may be used as a predictive marker in early sepsis in the future.