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The thalassemias are common genetic diseases among the Thai population. The
autooxidation of globin chains and iron overload are the suggested mechanisms for the
enhanced generation of reactive oxygen species and ensuing oxidative stress. It has been
reported that the oxidative stress alters function of the drug metabolizing enzymes system.
However, several cellular adaptive compensations against oxidative stress may modify the
outcome of the activity of the enzymes. The aim of this study was to evaluate the drug
metabolizing enzyme status in thalassemia patients, particularly to examine the activity of
CYP1A2, and to determine factors influencing its activity. The study included the regular
blood transfusion β-thalassemia I HbE patients (n = 23) and the healthy controls (n = 25).
The CYP1A2 activity was assessed by using caffeine as a probe drug. The caffeine and
its major metabolite, paraxanthine, in saliva and plasma at 6 h after drug intake, were
analyzed by high performance liquid chromatography (HPLC). The enzyme activity was
determined from the caffeine metabolic ratio (CMR), paraxanthine I caffeine. The oxidative
status was quantified by measuring the concentrations of plasma and whole blood total
glutathione. Moreover, the concentrations of hemoglobin, uric acid, total bilirubin. ALT
and AST were analysed in both groups. The results showed that the salivary CMR
highly correlated with the plasma CMR (r = 0.9772, p = 0.0001). The salivary and plasma
CMR in thalassemia patients were not significantly different in comparison with the
control group (plasma CMR : 0.759 ± 0.043 vs 0.775 ± 0.062 for control group and
thalassemia patients, respectively). Similarly, there was no significant difference between
the two groups in the concentrations of plasma total glutathione, whereas, the whole
blood total glutathione was significantly decreased in thalassemia patients (p < 0.05).
Correlations between parameters were analysed by using multiple linear regression
analysis. In the control group, none of the parameters correlated with the CMRs. In
contrast, the plasma CMR correlated significantly with the concentrations of total
glutathione, total bilirubin, ALT and AST in the thalassemia patients (r = 0.65 , p < 0.05).
In conclusion the CYP1A2 activity in thalassemia patients was not significantly altered
and its activity in these patients may be affected by the oxidative stress responses.
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