Protein Information

ID 613
Name alcohol dehydrogenase (protein family or complex)
Synonyms ADH; alcohol dehydrogenase; alcohol dehydrogenases

Compound Information

ID 1391
Name carbon disulfide
CAS carbon disulfide

Reference

PubMed Abstract RScore(About this table)
8861782 Khan S, Sood C, O'Brien PJ: The involvement of cytochrome P4502E1 in 2-bromoethanol-induced hepatocyte cytotoxicity. Pharmacol Toxicol. 1996 Apr;78(4):241-8.
The cytotoxicity of 2-bromoethanol towards hepatocytes isolated from rats was concentration-dependent (EC (50) 100 mu M, 2 hr). Bromoacetaldehyde was more toxic (EC (50) 60 mu M, 2 hr) and bromoacetic acid was less toxic (EC (50) 150 mu M, 2 hr). Glutathione (GSH) depletion occurred before cytotoxicity ensued and GSH depleted hepatocytes were more susceptible to 2-bromoethanol. Lipid peroxidation increased steadily 1 hr after 2-bromoethanol addition and antioxidants, iron chelators or hypoxia prevented 2-bromoethanol induced lipid peroxidation and cell lysis. Alcohol dehydrogenase inhibitors, methyl pyrazole or dimethyl sulfoxide only partly prevented 2-bromoethanol induced GSH depletion, lipid peroxidation and cytotoxicity. However, cytochrome P4502E1 (CYP2E1) inhibitors/substrates were more effective at preventing 2-bromoethanol-induced GSH depletion, lipid peroxidation and cytotoxicity suggesting that 2-bromoethanol is mostly metabolically activated by CYP2E1. Also, hepatocytes isolated from CYP2E1 induced rats were more susceptible to 2-bromoethanol and hepatocytes isolated from rats pretreated with carbon disulfide to inactivate CYP2E1 were more resistant to 2-bromoethanol treatment. Formation of S-(formylmethyl) glutathione during 2-bromoethanol metabolism by microsomal mixed function oxidase in the presence of GSH was also prevented by cytochrome P4502E1 inhibitors/substrates or by Anti-Rat CYP2E1. Furthermore, aldehyde dehydrogenase inhibitors-cyanamide or chloral hydrate increased 2-bromoethanol dependent hepatocyte susceptibility. This suggests that 2-bromoethanol is preferably metabolised by CYP2E1 dependent monoxygenase to form 2-bromoacetaldehyde which causes cell lysis as a result of GSH depletion and lipid peroxidation.
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