THE RELATIONSHIP BETWEEN NITRIC OXIDE PATHWAY AND LIPID PEROXIDATION IN SEPSIS

Summary Septic shock is the leading cause among intensive care unit deaths and the gastrointestinal tract has been defined as the motor of sepsis in the development of multiorgan failure. During sepsis, both nitric oxide synthesis and peroxynitrite production are enhanced in a variety of tissues, effects which favor the development of lipid peroxidation. Under the light of these data the preventive role of L-arginine and aminoguanidine (a relatively selective inhibitor of INOS) on lipid peroxidation and on histopathology of ileum in lipopolysaccharide (LPS) induced sepsis are studied. Thirty-six mice, weighing 25-30 g were divided into six equal groups. The first group, serving as control, received intraperitoneal (IP) 0.9 per cent saline 1 ml kg -1. The second group (sepsis group) received IP endotoxin (E.coli lipopolysaccaride 0.55:B5 10 mg kg-1, Sigma,USA). The third and the fourth groups received IP aminoguanidine (aminoguanidine hemisulphate 15 mg kg-1, Sigma, USA) 20 min before saline and endotoxin respectively. The fifth and the sixth groups received IP L-arginine (Sigma, USA) 20 min before saline and endotoxin respectively, for preventive aims. Six hours later, ali of the animals were anaesthetized and blood and ileal samples were obtained. Malondialdehyde (MDA) levels were studied and histopathological evaluation were done. The lipid peroxidation increased in the sepsis group seemed to be attenuated by L-arginine in the sixth group but the difference was statistically insignificant due to the high standard deviation value. Deep mucosal ulcer and local necrosis with massive inflamation were mainly observed in the sepsis group and in the IV. group histologic findings were similar to saline only-group. These data indicate that exogenous endotoxin applied to the animals broke down ileal histopathology. The preventive L-arginine given before endotoxin preserved ileal histopathology in sepsis and decreased lipid peroxidation although the difference was not statistically significant. Key Words: Sepsis, Nitric oxide, L-Arginine, Aminoguanidine, Lipid peroxidation OZET Sepsiste artan oksidan stres ile mortalite arasindaki iliski dusunuldugunde; L-arjinin depolarinda tukenme olmaksizin, endojen antioksidan olarak cNOS kokenli nitrik oksit (NO)'nun pulsatil saliverilmesi cok onemlidir. Calismamizda lipopolisakkarit (LPS) ile olusturulan deneysel sepsiste lipid peroksidasyonu uzerine NO'nun etkisi incelenmistir. 20-25 g. agirliklarinda 36 adet erkek fare alti gruba ayrildi: I. Grup: Kontrol(K), II. Grup: Sepsis(S), III. Grup: K + Aminoguanidin(AG), IV. Grup: S + AG, V. Grup: K+ L-Arjinin ve VI. Grup: S + L-Arjinin. Korunma amacli, kontrol gruplari icin SF, sepsis gruplari icin LPS verilmeden 20 dk. once I. ve II. gruplara plasebo olarak SF, III. Ve IV. gruplara AG, V. ve VI. gruplara L-arjinin verildi. Intraperitoneal verilen ajanlar SF 0.5 ml/kg, LPS 10 mg=0.5 ml/kg, AG 15mg=0.5 ml/kg, L-Arjinin 600 mg=0.5 ml/kg. dozlarda kullanildi. Deneklere 6. saatin sonunda eter anestezisi uygulandi. Lipid peroksidasyonun son urunu olan kan malondialdehit (MDA) degeri K. Yagi yontemiyle olculdu. Ileum histopatolojisi H. E. boyasiyla, skorlama sistemi kullanilarak degerlendirildi. Kontrol grubu ile sepsis grubunda ortaya cikan anlamli histopatolojik fark, sepsiste L-arjinin tedavisi ile AG tedavisi arasinda da ortaya cikmistir. Gruplar arasi kan MDA degerleri arasinda gozle gorunur matematiksel fark olmasina ragmen, denek sayisinin az olmasindan dolayi fark istatistiksel onemlilige ulasmamistir. Sepsiste ortaya cikan oksidan stresin, korunma amacli verilen L-arjinin ile karsilanmasinin dokularin yasayabilirliginde cok onemli oldugu ve NO'in sepsiste dengede tutulmasi gerektigi sonucuna varildi. Anahtar Kelimeler: Sepsis, Nitrik Oksit, L-Arjinin, Aminoguanidin, Lipid peroksidasyon