ACTA FAC. MED. NAISS. 2003; 20 (3): 183-188 |
Original article
EFFECTS OF CAPTOPRIL ON
MEMBRANE-ASSOCIATED ENZYMES IN LEAD-INDUCED HEPATOTOXICITY IN RATS
Tatjana Jevtović-Stoimenov, Gordana Kocić,
Dušica Pavlović, Ivana Stojanović,
Tatjana Cvetković, Dučan Sokolović,
Jelena Bašić Institute of
Biochemistry, School of Medicine, University of Niš
Ass. Dr Tatjana
Jevtović Stoimenov,
tjevtovic@yahoo.com
SUMMARY
The critical interest in lead poisoning arises from the fact that
industrialization led to general population lead poisoning by increasing the
whole body lead content from 2 to 200 mg. Since the inhibition of
delta-ALA-dehydratase (d-ALAD) is the main mechanism of lead toxicity, and
taking into account the pro-oxidant effects of d-ALA, the aim of this study was
to investigate the possible protective effects of captopril (SH-containing ACE
inhibitor) on lead -induced liver injury as well as membrane-associated enzyme
activity. The experiment was carried out on female rats (Sprague-Dawley, 150g,
12 weeks old) allocated to the following groups: I group was a control one ; II
group was treated with Pb-acetate (25mg/kg b.w.i.p. daily, during 5 days); III
group received captopril (100 mg/kg b.w.i.p. daily during 5 days); IV group was
treated with both agents simultaneously. PbAc caused significant depletion of
ALA-D activity (mmol/gHb/ml/h) in liver, blood, and bone marrow (p<0.05). In
rats treated with captopril and PbAc the activity of liver and bone marrow ALA-D
was completely recovered but not in blood. In the experimental model of acute
lead poisoning our results showed some significant changes in
membrane-associated enzymes, the increase of liver ALP, no change in plasma ALP,
the increase in liver and plasma GGT (p<0.05) and the decrease of liver 5'-NT
(p<0.05). In lead exposed animals, pre-treated with captopril, the activity of
membrane associated enzymes was fully recovered.
The apparent tendency of captopril to normalize the lead-induced inhibition of
heme synthesis and the assumption of oxidative damage as a mechanism in lead
toxicity suggests that SH-containing antioxidative agent captopril may play an
important role in the therapy of lead poisoning.
Key words: alkaline phosphatase, 5' - nucleotidaze, g - gamma-glytamil
transferase, lead, liver