The effect of aminoguanidine on blood and tissue lipid peroxidation in jaundiced rats with endotoxemia induced with LPS.
Obstructive jaundice (OJ) is a severe condition that leads to several complications. One of the important problems in OJ is the increased incidence of endotoxemia, which is the result of bacterial translocation (BT) and defective host immune response. Lipid peroxidation (LP) is an important problem in OJ and sepsis in which nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity are increased and antioxidative activity is decreased. Formation of peroxynitrite (ONOO(-)) anion leads to cellular damage and apoptosis. In this experimental study, we explore the effect of specific iNOS inhibitor aminoguanidine (AG) on blood and tissue (liver and renal) LP and iNOS levels in jaundiced rats with endotoxemia induced with lipopolysaccharide (LPS). Rats were randomized into six groups; group A, sham; group B, obstructive jaundice (OJ); group C, OJ + LPS; group D, OJ + AG; group E, OJ + LPS + AG; group F, OJ + AG + LPS. Serum malondialdehyde (MDA) and serum myeloperoxidase (MPO) activity and liver and renal tissue MDA, MPO, and Na(+)/K(+)-ATPase activity levels were detected in biochemical methods. Liver and renal tissue iNOS levels were examined immunohistopathologically. Serum and tissue MDA and MPO levels and tissue iNOS expression were increased significantly in groups B, C, and E, while tissue ATPase levels were decreased significantly in the same groups. In the group treated with AG (group D), serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. In group F, if AG was administrated before LPS, we observed that serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. Thus, our study showed that AG had a protective effect when it was administrated before LPS, but it failed to prevent tissue iNOS expression and LP if there was established endotoxemia in OJ.
Ogetman
Zekai
Z
Department of General Surgery, Mersin University Medical School, Mersin, Turkey.
Dirlik
Musa
M
Caglikulekci
Mehmet
M
Canbaz
Hakan
H
Karabacak
Tugba
T
Yaylak
Faik
F
Tamer
Lulufer
L
Kanik
Arzu
A
Aydin
Suha
S
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D019446:Endotoxemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D007150:Immunohistochemistry; D041781:Jaundice, Obstructive / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D009195:Peroxidase / Q000097:blood / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D008315:Malondialdehyde; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000251:Adenosine Triphosphatases; C004479:pimagedine