Glutathione depletion by 2-nitroimidazole-1-acetohydroxamic acid as a radiosensitizer in hypoxic rat hepatocytes.

Abstract

The effects of nitroimidazoles as radiosensitizers on intracellular glutathione (GSH) level were investigated in rat isolated hepatocytes. Dinitroimidazoles have lowered almost completely GSH level during the incubation for 30 min under oxic (95% O2+5% CO2) condition, while mononitroimidazoles had scarcely affected. In the case of hypoxic (95% N2+5% CO2) condition, however, 2-nitroimidazoles, not 4-nitroimidazoles, as well as 2,4- and 4,5-dinitroimidazoles have caused the significant depletion of GSH. This suggests that nitro group in the 2-position of imidazoles may be responsible for the GSH depletion under hypoxia. Especially, 2-nitroimidazole-1-acetohydroxamic acid (KIH-801) was found to be the most potent GSH depletor only under hypoxic, not oxic conditions, and might be useful for the new hypoxic cell radiosensitizer instead of misonidazole.

• Authors: K Takanuki, T Igarashi, K Hata, H Hori, T Shibata, H Kitagawa, T Satoh, S Inayama
• Journal: Biochemistry international (Biochem Int) Vol. 17 Issue 1 Pg. 155-62 (Jul 1988) ISSN: 0158-5231 [Print] Australia
• PMID: 3190713 (Publication Type: Journal Article)

Chemical References

• Hydroxamic Acids
• Nitroimidazoles
• Radiation-Sensitizing Agents
• 2-nitroimidazole-1-acetohydroxamic acid
• Glutathione
• Oxygen

Topics

• Animals
• Glutathione (metabolism)
• Hydroxamic Acids (pharmacology)
• In Vitro Techniques
• Liver (drug effects, metabolism)
• Male
• Nitroimidazoles (pharmacology)
• Oxygen (physiology)
• Radiation-Sensitizing Agents (pharmacology)
• Rats
• Rats, Inbred Strains
• Structure-Activity Relationship