Mechanisms of apomorphine cytoxicity towards rat glioma C6 cells: protection by bovine serum albumin and formation of apomorphine-protein conjugates.
Apomorphine cytotoxicity towards rat glioma C6 cells was recently demonstrated to be time- and concentration-dependent. In the present work, the mechanism of cytotoxicity of apomorphine was further studied in the C6 cell line. We showed that bovine serum albumin partially protects C6 cells against apomorphine cytotoxicity. However, serum albumin did not prevent apomorphine autoxidation and melanin formation, suggesting that this protein scavenges apomorphine reactive products formed during its oxidation. The use of radioactive tracers, fluorimetry and protein electrophoresis showed that apomorphine autoxidation products covalently and nonspecifically bind to serum albumin and to rat liver microsomes. L-Cysteine, which is a thiol reagent that inhibits apomorphine autoxidation also prevented the formation of apomorphine-serum albumin adducts. These results suggest that quinone derivatives formation and oxidative stress should be responsible for apomorphine cytotoxicity.
El-Bachá
R S
RS
UMR CNRS-Université Henri Poincaré No. 7561, Laboratoire de Pharmacologie, Faculté de Médecine, Vandoeuvre-lès-Nancy, France.
Netter
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Minn
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D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016166:Free Radical Scavengers; D005910:Glioma; D008543:Melanins / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016166:Free Radical Scavengers; D008543:Melanins; D012710:Serum Albumin, Bovine; D001058:Apomorphine