Hronično unošenje hlorpromazina izaziva inhibiciju intracelularne biohemijske aktivnosti moždanog tkiva miša
Chlorpromazine treatment induced inhibition of intracellular biochemical activity of mouse brain tissue
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Chlorpromazine (CPZ), an antipsychotic drug, was found to inhibit intracellular carboxylesterases (CarbEs). As intracellular target carboxylesterases we used alpha-naphthyl acetate esterase (alpha-NA), naphthol AS-D chloroacetate esterase (AS-D) and alpha-naphthyl butyrate esterase (alpha-NB) in mouse polymorphonuclear neutrophils (PMN), hepatocytes (HC) and neuronal brain cells (NC). The impact of CPZ on the cells ranged from no effect to death, with intermediary effects of decreased CarbEs activities without either morphological changes or structural changes. The results of our study indicate that intracellular CarbEs activity inhibition by CPZ was dose-dependent, though the drug concentration required to bring about 50% inhibition of the initial activity (ID-50) varied between the mouse cell types, under the same experimental conditions. CarbEs activity was decreased or completely inhibited at CPZ concentrations ranging from 0.5 to 5.0 mg/ml (1.4 to 14.08 mmol/l). The impact maximum concentration of CPZ 5 mg/ml (14.08 mmol/l) on mouse brain cells resulted in 46.58% inhibition for AS-D, 54.26% for α-NA and 99.52% for α-NB. Our studies established a clear relationship between the increasing concentrations of CPZ and the extent of inhibition of the intracellular esterases of mice. Correlation of the inhibitory effects in all the cell types was demonstrated. The polymorphonuclear neutrophils - leukocytes were the most sensitive (ID-50 = 0.42 mg CPZ/ml) and the hepatocytes most resistant to the CPZ effect (ID-50 = 2.45 mg CPZ/ml). Since leukocytes are human cells much more readily available than hepatocytes or neuronal cells, we presume that CarbEs in peripheral blood leukocytes could be used as markers for the indication of intracellular biochemical damage of hepatocytes and neuronal brain cells by CPZ.
Source:Acta veterinaria, 2000, 50, 5-6, 361-373