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To study the effect of erythromycin on cytochrome P-450 (CYP) and its mechanism. The conversion of testosterone to 6beta-OH-testosterone (6beta-OH-T) by rat hepatic microsomes was used to study the in vitro inhibition of erythromycin on rat liver CYP. The activity of CYP and the content of erythromycin in the incubation medium were determined by HPLC. The inhibition effect of erythromycin on CYP was time- and concentration-dependent. The IC50 value of erythromycin on hepatic microsomes was 57.22 micromol x L(-1), and the IC50 value of erythromycin on 6beta-OH-testosterone was 45.82 micromol x L(-1). The inhibition by erythromycin on CYP was not reversible. The activities of CYP and the content of erythromycin in the medium were decreased in the presence of erythromycin. The anti-bacterial activity of erythromycin was also decreased. Erythromycin can not only inhibit CYP and its activity, but also accumulate in the microsome.Ascorbic acid-induced inhibition of 6-formyl pyridine-N-oxide and nitrotyrosine formation in parallel with the reduction of brain damage in rats following transient forebrain ischemia.
We used a 6-formyl pyridine-N-oxide (FPNO) and anti-nitrotyrosine antibody to investigate the possible relationships between NO and the production of tyrosine nitration products in ischemic brain. Rats were subjected to a 20-min ischemic insult and then the brains were removed at 4 h postischemia. At 30 min after ischemia, 5-microliter intracerebral injection of N-nitro-L-arginine (L-NNA), an irreversible inhibitor of nitric oxide synthase, was made into the right striatum. FPNO, which is a stable derivative of NO
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