Role of effectors on hypoxia due to nitric oxide production in human alveolar epithelial cells and oxygen depletion in human hepatocytes: Part II. A tool of nitroimidazole cytotoxicity asessment

Nitroimidazole is an antibiotic and radiosensitizer chemical with great potentials inimaging. Cytoxicity evaluation of nitroimidazole and possible changes in energy statusdue to its anti-inflammatory characteristics are crucial in tumor imaging andchemotherapy. Adenylate cyclase is key enzyme to cause energy imbalance leading tocytotoxicity. To evaluate energy status in hepatocytes and Kupffer cells, adenylatecyclase activities in isolated liver cells were compared in the presence of severalstimulators. To evaluate the effect of stimulators on adenylate cyclase in culturedhepatocyte cells, adenylate cyclase enzyme was stimulated by different GITP, GTP,progesterone and nitroimidazole effectors. In cultured Kupffer cells, prostaglandin E2 andF2α were used as effectors. The results showed that nitroimidazole decreased adenylatecyclase specific activity in dose-dependent manner after pre-incubation of hepatocyteswith the nitroimidazole in the medium. Nitroimidazole stimulated adenylate cyclaseactivities in hepatocytes were mediated by cAMP and determined by cAMP mesurement.The stimulatory effect of nitroimidazole on adenylate cyclase was independent of thepresence of GTP. This stimulatory effects may be due to a direct effect on the catalyticsubunit of adenylate cyclase enzyme. In addition, basal cAMP generation in hepatocyte cells was efficiently suppressed by the nitroimidazole. In conclusion, nitroimidazole exhibits direct effect on the catalytic subunit of the adenylate cyclase system. The adenylate cyclase was hormone sensitive in liver cells.