الفهرس | Only 14 pages are availabe for public view |
Abstract Cytochrome P450 1A2 (CYP1A2) is involved in the metabolism of many medications as well as in the activation of many pro-carcinogens. Modulations of CYP1A2 enzyme activity and inducibility are associated with adverse drug reactions besides increased risks of several malignancies. Similarly, CYP1A2 is affected by several factors which are involved in the pathogenesis of depression such as psychological stress, increased inflammatory cytokines and increased glucocorticoids. Depression is a leading contributor of the global burden of diseases with several comorbidities. Understanding the status of CYP1A2 in depressed patients would add to our knowledge regarding the pharmacokinetics of CYP1A2 substrates in depressed patients and may help in understanding the links between depression and some of its comorbidities, as myocardial infarction and some types of malignancies which can also be affected by CYP1A2 genotypic or phenotypic variations. In the present work, the aim was to study the impact of chronic mild stress model of depression ‘CMS’ on the activity and inducibility of CYP1A2 isozyme in male Wistar rats. To evaluate the response of rats to the model, a package of three behavioral tests used. The package include sucrose preference test ‘SPT’, Forced swimming test ’FST’ and open field test ‘OFT’. Caffeine ‘CA’ is the metabolic probe that used to assess CYP1A2 enzyme activity and inducibility. Metabolic ratios of CA and its primary metabolites namely, theobromine ‘TB’, paraxanthine ‘PX’ and theophylline ‘TP’ are markers of CYP1A2 activity. The same markers used also, to test the inducibility of CYP1A2 by o-toluidine. chronic mild stress is a rodent model of depression with excellent face validity, constructive validity and predictive validity. |