Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Mechanisms of apomorphine cytoxicity towards rat glioma C6 cells: protection by bovine serum albumin and formation of apomorphine-protein conjugates. 1021 2

Many catechol derivatives are currently used as drugs, even if they produce reactive oxygen species that may cause tissue damage. Among them, apomorphine, a potent dopamine agonist, displays efficient anti-parkinsonian properties, but the consequences of its oxidant and toxic properties have been poorly investigated on in vitro models. In the present work, we investigated apomorphine cytotoxicity by incubating cultures of rat glioma C6 cells and primary cultures of neurons with different concentrations of the drug. Apomorphine-promoted cell death was proportional to its concentration and was time-dependent. The ED(50) of apomorphine on C6 cell death after 48 hr was about 200 microM. The cytotoxic effects induced by apomorphine were correlated to its autoxidation, which leads to the formation of reactive oxygen species, semiquinones, quinones, and a melanin-like pigment. C6 cells that underwent treatment with 400 microM apomorphine for 6 hr displayed features of necrosis, including loss of membrane integrity, degeneration of mitochondria, and DNA fragmentation. Thiols, such as cysteine, N-acetyl-L-cysteine, and glutathione, significantly protected cultured neurons and C6 cells against apomorphine-induced cytotoxicity. Thiols also inhibited apomorphine autoxidation. These data strongly suggest that apomorphine cytotoxicity towards neurons and C6 cells results from an intracellular oxidative stress.
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PMID:Toxic effects of apomorphine on rat cultured neurons and glial C6 cells, and protection with antioxidants. 1113 12