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Acta Medica Medianae
Vol. 45
Number 1, Januar, 2006
UDK 61
YU ISSN 0365-4478



Dušan Sokolović
Department of biochemistry Faculty of Medicine of Nis
81 dr Zorana
Djindjic Street
18000 Ni
s, Serbia and Montenegro
018/ 226-644, lok. 131
E-mail: soko@medfak.ni.ac.yu




Copyright 2006 by Faculty  of Medicine, University of Nis



Dusan Sokolovic 1, Gordana Bjelakovic 2, , Saša Zajić 3, Zoran Damnjanović 4, Jelenka Nikolić 1, Gordana Kocić 1, Dušica Pavlović 1, Ivana Stojanović 1 i Tatjana Cvetković 1

Department of biochemistry Faculty of Medicine of Nis1
Department of Pathofiziology Faculty of Medicine of Nis2
Hospital of
Krusevac 3
Sanofi Aventis 4

The pathogenesis of encephalopathy in cholestasis results from the accumulation of unconjugated bilirubin (UCB) and hydrophobic bile acids (BA) in the brain. Toxic BA and UCB induce neurotoxicity, and  being transported across the blood-brain barrier they are accumulated in the target neurons. Putrescine, spermidine and spermine are endogenous polyamines essential for cellular growth, proliferation, regeneration and differentiation. Amino-acid L-methionine (L-met) is required for biosynthesis of polyamines.
The aim of the study was to examine the effect of L-met in polyamine metabolism  on cholestatic brain of  injured rats.
Wistar rats were divided into 5 groups: I-control, II-sham operated rats, III-treated only with L-met, IV-bile duct ligated (BDL) rats, V-BDL rats treated with L-met (50 mg/kg BW). The animals were sacrificed after 9 days of treatment.
Increased concentration of plasma cholestatic markers (bilirubin and BA) in BDL rats was decreased by oral administration of L-met (p < 0.001).
Cholestasis in rats’ brain increases the putrescine level (11013.2 vs. 656.8 nmol/g; p < 0.001) and decreases spermidine (29819.2 vs. 31819.5 nmol/g; p < 0.05) and spermine concentration (20316.2 vs. 22512.7 nmol/g; p < 0.05) in relation to sham operated rats. The increase of putrescine level after CNS trauma is adaptive neuroprotective responses. Administration of L-met in BDL rats prevents disorder of polyamines’ biosynthesis and in the brain during cholestasis.
L-met is important for the regulation of polyamines’ metabolism and demonstration of neuroprotective role in cholestasis. Acta Medica Medianae 2006; 45(1):21-26.

 Key words: polyamines, cholestasis, L-methionine, brain