Issue: Vojnosanit Pregl 2016; Vol. 73 (No. 4)

Oxidative stress induced by chlorpromazine in patients treated and acutely poisoned with this drug

Authors:
Bratislav Dejanović, Vesna Vuković-Dejanović, Ivana Stevanović, Ivana Stojanović, Gordana Mandić Gajić, Sanda Dilber

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Abstract
Background/Aim. Although chlorpromazine (CPZ) is an antipsychotic
drug widely used in clinical practice for a long time, its
mechanism of action has not been entirely defined. An extremely
difficult managing of patients acutely poisoned with CPZ is additional
reason for detailed studying its toxicity mechanisms. In this
clinical study, we investigated whether the oxidative stress (OS)
mediates CPZ toxic effects in the exposed patients. Methods. The
patients were organized into 3 groups: the T-group – hospitalized
patients receiving therapeutic doses of 75–150 mg CPZ/day; the
overdosed group, divided into two subgroups: the group M and
the group S – mildly (CPZ serum concentration: 0.21 ± 0.05
mg/L) and severely (CPZ serum concentration: 2.66 ± 0.25 mg/L)
poisoned patients, respectively, and the group C (control group of
healthy volunteers). Oxidative stress parameters [total antioxidative
status (TAS) and malondialdehyde (MDA) in plasma)] and superoxide
dismutase (SOD) activity in erythrocytes were measured
spectrophotometrically, and CPZ concentrations in serum were
monitored chromatographically. One set of measurements was
performed in the group C and T, whereas two sets of measurements
(after 24 hours and 48 hours) were done in the poisoned patients,
groups M and S. Results. A decrease of TAS and increase
of SOD activity were obtained in both subgroups of the poisoned
patients, compared to the controls and the group receiving therapeutic
doses of CPZ. A significant increase of MDA was achieved
in severely poisoned patients, compared to all other groups. Conclusion.
Changed oxidative stress parameters in patients poisoned
with chlorpromazine indicate involvement of oxidative stress in
the toxicity mechanism(s) of chlorpromazine.
Key words:
chlorpromazine; poisoning; oxidative stress;
malondialdehyde; superoxide dismutase.