کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2603855 | 1133840 | 2007 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Estimating constants for metabolism of atrazine in freshly isolated rat hepatocytes by kinetic modeling Estimating constants for metabolism of atrazine in freshly isolated rat hepatocytes by kinetic modeling](/preview/png/2603855.png)
This study estimated the kinetic constants for oxidative metabolism of atrazine (ATRA) and its chlorotriazine (Cl-TRI) metabolites, 2-chloro-4-ethylamino-6-amino-1,3,5-triazine (ETHYL), 2-chloro-4-amino-6-isopropylamino-1,3,5-triazine (ISO), and diaminochlorotriazine (DACT), using freshly isolated rat hepatocytes. Hepatocytes were incubated with 1.74, 44, 98, and 266 μM ATRA. Disappearance of ATRA and formation of the Cl-TRI metabolites were quantified over 90 min. At all incubation concentrations, ATRA was preferentially metabolized to ETHYL, producing ETHYL concentrations approximately 6 times higher than those of ISO. DACT concentrations peaked at 44 μM ATRA and decreased with increasing incubation concentrations, indicating non-linear metabolic behavior of ATRA with respect to DACT formation. A series of kinetic models were developed from these data to describe the dose and time-dependent oxidative metabolism of ATRA and the Cl-TRI metabolites. An integrated model for all the chloro-triazines included multi-substrate competitive inhibition of metabolism to describe the non-linear behavior of DACT production in relation to ATRA while simultaneously simulating the time-course behavior of the Cl-TRIs at all four ATRA concentrations. The maximal metabolic rate (Vmax) of ATRA metabolism and the Michaelis–Menten constant (KM) for the reaction were 1.6 μM/min and 30 μM, respectively. Vmax and KM values for ETHYL and ISO metabolism to DACT were also estimated using this modeling approach.
Journal: Toxicology in Vitro - Volume 21, Issue 3, April 2007, Pages 492–501