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Acta Medica Medianae
Vol. 45
Number 2, April, 2006
UDK 61
YU ISSN 0365-4478



Dusan Sokolovic
Department of biochemistry
Faculty of Medicine
81 Dr Zoran Djindjic Street
18000 Nis
E-mail: soko@medfak.ni.ac.yu




Copyright 2006 by Faculty  of Medicine, University of Nis


Dusan Sokolovic 1, Gordana Bjelakovic 1, Jelenka Nikolic 1, Gordana Kocic 1, Boris Djindjic 2, Dusica Pavlovic 1, Stojan Radic 2, Jelena Basic 1,  Marko Jovic and Dimitros Koutsonanos 3

Department of biochemistry Faculty of Medicine of Nis1
Department of Pathofiziology Faculty of Medicine of Nis2
Hospital of Thessaloniki 3

Encephalopathy in cholestasis results from accumulation of unconjugated bilirubin (UCB) and hydrophobic bile acids (BA). Toxic BA and UCB induces neurotoxicity (apoptosis of neurons). Putrescine, spermidine and spermine are endogenous polyamines essential for cellular growth, regeneration and differen-tiation. Beneficial effects of putrescine in CNS injury have been attributed to anti-apoptotic ant anti-oxidant properties.
The aim of the study was to examine the effect of putrescine at the level of
lipid peroxidation in cholestatic brain injury.
Wistar rats were divided into 5 groups: I-control, II-sham operated rats, III-treated only with putrescine, IV-bile duct ligated (BDL) rats, V-BDL rats treated with putrescine (150mg/kg BW ip.). The animals were sacrificed after the 9 -day treatment.
Administration of putrescine in BDL rats reduces concentration of blood plasma UCB and BA (29.23.3 vs. 43.65.9 μmol/l and 11.40.8 vs. 22.82.6 μmol/l; p < 0.001). The lipid peroxidation
(MDA) was increased in brain of BDL rats (4.980.54 vs. sham operated rats 3.990.32 nmol/mg prot; p < 0.001). Putrescine decreased MDA level in brain of V group vs. IV group rats (2.250.42 vs. 4.980.54 nmol/mg p; p < 0.001). The amplification of cerebral activity of polyamine oxidase (PAO) in BDL rats (1.250.09 vs. sham operated rats 0.810.09 U/mg prot; p < 0.001), resulted in high local concentrations of 3-acetamidopropanol and H2O2 which lead to oxidative stress and cell death. Administration of putrescine of BDL rats, decreased activity of cerebral PAO compared with BDL rats (1.020.07 vs. 1.250.09 U/mg prot; p < 0.001).
Administration of putrescine in BDL rats results in normalization of cerebral oxidative stress and has protective role after the CNS injury in cholestasis.
Acta Medica Medianae 2006;45(2):45-51.

Key words: putrescine, lipid peroxidation, cholestasis, brain