Modification of CYP2E1 and CYP3A4 activities in haemoglobin E-beta thalassemia patients

摘要: Thalassemia disease is a genetic haemoglobinopathy usually associated with an iron overload and some degree of organ impairment. The impact the on drug metabolising enzyme cytochrome P450 (CYP) not known. CYP2E1 CYP3A4 are responsible for metabolism large number drugs changes in their activities may have clinical consequences. Haemoglobin E-β thalassemia paediatric, blood transfusion-dependent patients apparently without complications (n = 35) healthy controls (n = 42) were recruited this study. ratios plasma 6-hydroxychlorzoxazone to chlorzoxazone, urinary 6-beta-hydroxycortisol (6β-OHF) cortisol used as indices activities, respectively. Blood samples assayed parameters biochemistry, oxidants antioxidants. There significant increases serum iron, protein carbonyl lipid peroxidation patients, whereas there was decrease glutathione, but unchanged nitric oxide metabolites. activity unchanged; however, when stratified by splenectomy status, increased non-splenectomised comparison splenectomised subjects. On other hand, 6β-OHF/cortisol markedly depressed growth hormone levels. no correlations between oxidant stress or antioxidant parameters. This report first demonstration that major alteration activities; could modify sensitivity toxic therapeutic effects drugs.