Abstract:
:The mechanisms of toxicity and sensitization by the radiosensitizer misonidazole [1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol] are not well understood. We report here on the inhibition of total glutathione peroxidase (GSHPx), selenium-dependent glutathione peroxidase (selenium-GSHPx) and glutathione transferase (GSHTx) activities by misonidazole. Mouse liver cytosol GSHPx and selenium-GSHPx were inhibited in vitro with 0.5 mM misonidazole. On administration of the drug intraperitoneally (800 mg/kg) to mice, it was found that GSHPx, selenium-GSHPx, and GSHTx were inhibited in homogenate, cytosol, and microsomal fractions of mouse liver. GSHPx was depressed in all fractions up to 60-70% of control values, with maximum depression occurring in the cytosol and homogenate fractions in less than 2 hr. Recovery of activity was slower in the microsomes. In general, the pattern of depression of selenium-GSHPx was parallel to that of GSHPx except in microsomes, where GSHPx is minimal. Quantitatively, selenium-GSHPx was least affected. GSHTx was inhibited 70-80% of control values in cytosol and homogenate with recovery by 24 hr, whereas a second period of depression occurred at 24 hr in the microsomes. The inhibition of peroxide-metabolizing enzymes may lead to elevation of intracellular peroxide levels, contributing to the radiosensitizing effect and/or toxicity of misonidazole.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Kumar KS,Weiss JFdoi
10.1016/0006-2952(86)90399-0subject
Has Abstractpub_date
1986-09-15 00:00:00pages
3143-6issue
18eissn
0006-2952issn
1873-2968pii
0006-2952(86)90399-0journal_volume
35pub_type
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