ABSTRACT
Objective To detect content of 4-hydroxy-3-methoxy benzoic acid by RP-HPLC and observe the inhibitory effect of phloroglucinol on catecholamine-O-methyl transferase (COMT). Methods This study used the principle of 3,4-dihydroxy benzoic acid transforming to 4-hydroxy-3-methoxy benzoic acid under COMT’ s catalytic action. COMT (20 μL) was extracted from mouse liver homogenate. In a reaction system,10 μL catecol (1í10-3 mol·L-1 ) and 10 μL phloroglucinol (5í10-3 , 1í10-3 and 2í10-4 mol·L-1 ,respectively) were added. Products were determined by RP-HPLC to analyze effects of 4-hydroxy-3-methoxy benzoic acid on COMT. Results Phloroglucinol had inhibitory effect on COMT activity at concentrations of 5í10-3 mol·L-1 ,1í10-3 mol·L-1 and 2 í10-4 mol ·L-1 ,with the inhibition rate being 25. 3% ,17. 6% and 8. 9% ,respectively. Conclusion Phloroglucinol has an inhibitory effect on COMT activity,which is weaker than the effect of catechol of the same concentration.
ABSTRACT
In view of documented evidence that catechol estrogen-DNA adducts serve as epitopes for binding of anti-nuclear antibodies, genetic polymorphisms of the xenobiotic metabolic pathway involved in estrogen metabolism might contribute towards pathophysiology of systemic lupus erythematosus (SLE). To test this hypothesis, a case-control study was conducted. Cytochrome P 450 1A1 (CYP1A1) m4 (OR: 4.93, 95% CI: 1.31-18.49), catecholamine-o-methyl transferase (COMT) H108L (OR: 1.39, 95% CI: 1.03-1.88) and glutathione-S-transferase (GST) T1 null (OR: 1.83, 95% CI: 1.11- 3.01) variants showed association with SLE risk. SHEsis web-based platform analysis showed mild to moderate linkage disequilibrium between the CYP1A1 m1, m2 and m4 variants (D’: 0.19-0.37). Among the different haplotypes of CYP1A1, CAC-haplotype harboring CYP1A1 m1 variant showed association with SLE risk (OR: 1.46, 95% CI: 1.11-1.92). Multifactor dimensionality reduction analysis (MDR) showed potential gene-gene interactions between the phase II variants i.e. COMT H108L × GSTT1 null × GSTM1 null (p<0.0001) and also between the phase II and I variants i.e. COMT H108L × GSTT1 null × CYP1A1 m1 × CYP1A1 m2 in inflating the risk of SLE by 3.33-folds (95% CI: 2.30-4.82) and 4.00-folds (95% CI: 2.77-5.78), respectively. To conclude, hyperinducibility of CYP1A1 due to m1 and m4 variants and defective phase-II detoxification due to COMT H108L and GSTT1 null variants increase the susceptibility to SLE.