Effect of Chlorpromazine on Human and Murine Intracellular Carboxylesterases

L. Radenovic^1* and G. Kartelija²

¹Department of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, p.f. 52, Studentski trg. 16, 11000 Belgrade, Serbia and Montenegro; fax: (+381-11) 638-500; 639-064; E-mail: lira@ibiss.bg.ac.yu

²Institute for Biological Research, 29 November 142, 11060 Belgrade, Serbia and Montenegro; fax: (+381-11) 761-433; E-mail: kartg@ibiss.bg.ac.yu

^* To whom correspondence should be addressed.

Received April 29, 2003; Revision received September 5, 2003

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Clinical use of chlorpromazine (CPZ), an antipsychotic drug, is limited due to its hepatotoxicity. CPZ is found to inhibit in vitro intracellular carboxylesterases (CE), such as alpha-naphthyl acetate esterase, naphthol AS-D chloroacetate esterase, and alpha-naphthyl butyrate esterase in polymorphonuclear neutrophils, hepatocytes, and neuronal brain cells from mice. CPZ inhibits CE of all these cell types, whereby the degree of the inhibition depends on the incubation time and CPZ concentration. The polymorphonuclear neutrophils are most sensitive to CPZ. Comparable results were obtained with polymorphonuclear neutrophils from mice and humans. Since leukocytes are much more available than hepatocytes or neuronal cells in humans, we assume that CE in peripheral blood leukocytes (neutrophils and monocytes) can be used as markers for indication of pending liver damage by CPZ.

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KEY WORDS: carboxylesterase, chlorpromazine, hepatocytes, intracellular enzymatic activity, liver damage, neuron, polymorphonuclear neutrophils

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