Inhibition of Cytochrome P450 3A1/2 by Organotin Compound Di-N-Butyl-(4-chlorobenzohydroxamato)tin (IV) Chloride in Rat Liver and BRL Cells

Organotin compounds are high toxiferous chemicals and ubiquitous in our environment, which also have high biological activities. Di-n-butyl-(4-chlorobenzohydroxamato)tin (IV) chloride (DBDCT) represents a new paradigm for tin-based antitumor complexes with high activity. The inhibitory effect of DBDCT on cytochrome P450 3A(CYP3A) was studied in this article. The adult male SD rats were randomly divided into five groups with six in each and treated separately with saline, lipopolysaccharide (LPS, 5mg/kg), DBDCT (1.25, 2.5 and 5.0mg/kg, respectively) intraperitoneally for 2 days after induced with dexamethasone (DEX) at a dose of 100mg/kg for 4 days. The cytochrome P450 (CYP450) content was assayed by the method of Omura and Santa after the protein concentration detected by BCA assay kit. The activity of CYP3A was determined by the method of Nash. Western blot analysis was used to detect the expression of CYP3A1/2 at protein level in rat liver microsomes and Buffalo Rat Liver (BRL) cells. The results demonstrated that the activity of CYP450 and CYP3A were inhibited by exposure to DBDCT in rat liver compared with that of the blank control group. The expression of CYP3A1 and CYP3A2 proteins in rats treated with 1.25, 2.5 and 5.0mg/kg DBDCT were down-regulated respectively by 22.8% (p