Abstract:
:Bacillus megaterium contains a soluble cytochrome P450 termed BM-3, which is highly inducible by barbiturates, peroxisome proliferators, and nonsteroidal antiinflammatory drugs. In rats and mice, the chronic administration of peroxisome proliferators induces a sustained oxidative stress in hepatic tissue and may be responsible for the nongenotoxic carcinogenesis observed with prolonged treatment. Here it is shown that ibuprofen induces a variety of enzymes associated with the oxidative stress response in Bacillus, including catalase, glucose-6-phosphate-dehydrogenase, and aldehyde reductase in a dose-related manner. Furthermore, evidence is presented to show that the expression of cytochrome P450 in Bacillus is associated with a marked depletion in cellular glutathione levels and that it renders these cells considerably more sensitive to oxidant insult. Finally, this work reports that a variety of structurally diverse antioxidants such as ascorbic acid, reduced glutathione, alpha-tocopherol acetate and the artificial antioxidant, butylated hydroxyanisole, all dramatically attenuate the expression of the cytochrome P450BM-3 gene and its repressor, Bm3R1, following ibuprofen treatment. These observations provide the first evidence that the expression of cytochrome P450 genes can lead to increased oxidant sensitivity but can be strongly modulated by dietary and artificial antioxidants, as well as antioxidant enzymes. The important implications of this phenomenon are also discussed.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
English NT,Rankin LCdoi
10.1016/s0006-2952(97)00054-3subject
Has Abstractpub_date
1997-08-15 00:00:00pages
443-50issue
4eissn
0006-2952issn
1873-2968pii
S0006295297000543journal_volume
54pub_type
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