Investigations of interactions of chlormezanone racemate and its enantiomers on human keratinocytes and human leucoytes in vitro.
Chlormezanone is a centrally acting muscle relaxant introduced in human therapy as a racemic substance. The following investigation was performed in order to investigate whether the racemate and both enantiomers differ in their potential cytotoxicty in vitro. We investigated antiproliferative effects and cytotoxicity (PicoGreen and ATP assay) for human HaCaT keratinocytes, production of oxygen radicals (ROS) by human interleukin-3-stimulated leukocytes (Lucigenin assay) and production of sulfoleukotrienes (Cellular Antigen Stimulation Test - CAST) by human leukocytes. In the dosage range of 0.001 to 0.1 mg/ ml chlormezanone, no antiproliferative effects were measured with the racemate and both enantiomers. At 1.0 mg/ml, a decrease of proliferative activity was seen after 48 h incubation time of about 50% for the enantiomers and of about 80% for the racemate (PicoGreen) and 50% (enantiomers) or 21% (racemate) in the ATP assay, respectively. ROS production was significantly inhibited at concentrations < or =0.01 mg/ ml by the racemate and the (+)-enantiomer, whereas the (-)-enantiomer was less effective. There was no stimulation of sulfidoleukotrienes in human leukocytes by chlormezanone. Present data argue for absence of significant cytotoxicity against human HaCaT keratinocytes and a dose-dependent suppression of ROS production by human leukocytes that is not uniform among the racemate and its enantiomers.
Wollina
U
U
Department of Dermatology, Academic Teaching Hospital Dresden-Friedrichstadt, Germany. wollina-uw@khdf.de
Hipler
U-C
UC
Seeling
A
A
Oelschlager
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000485:Allergens; D002478:Cells, Cultured; D002720:Chlormezanone / Q000737:chemistry / Q000494:pharmacology*; D005456:Fluorescent Dyes; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D009125:Muscle Relaxants, Central / Q000737:chemistry / Q000494:pharmacology*; D009930:Organic Chemicals; D017382:Reactive Oxygen Species / Q000378:metabolism; D013237:Stereoisomerism
D000485:Allergens; D005456:Fluorescent Dyes; D007377:Interleukin-3; D009125:Muscle Relaxants, Central; D009930:Organic Chemicals; C099476:PicoGreen; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D002720:Chlormezanone