Number 1, Januar, 2006
YU ISSN 0365-4478
biochemistry Faculty of Medicine of Nis
81 dr Zorana
226-644, lok. 131
by Faculty of Medicine, University of Nis
EFFECT OF L-METHIONINE ON POLYAMINE METABOLISM IN
RATS’ BRAIN WITH CHOLESTASIS
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
Faculty of Medicine of Nis1
Department of Pathofiziology Faculty of Medicine of Nis2
Sanofi Aventis 4
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 (110±13.2 vs.
65±6.8 nmol/g; p < 0.001) and decreases spermidine (298±19.2 vs.
318±19.5 nmol/g; p < 0.05) and spermine concentration (203±16.2 vs.
225±12.7 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
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.
polyamines, cholestasis, L-methionine, brain