Mathuros RuchirawatJutamaad SatayavivadUdom ChantharaksriSara Arphorn2024-07-252024-07-25199219922024Thesis (M.Sc. (Toxicology))--Mahidol University, 1992https://repository.li.mahidol.ac.th/handle/20.500.14594/99844Toxicology (Mahidol University 1992)1,4 dichlorobenzene (DCB) is used extensively as a space deodorant, a household moth control agent and an intermediate in the production of dyes such as 2,5 dichlorophenol, insecticides, pharmaceuticals and other organic chemicals. It is well docunented that exposure to chemicals and nutritional status of the host can alter the pharmacological and toxicological action of the other compound by interfering with the activity of the metabolizing enzymes system in the liver microsomes. Therefore, the effect of exposure to DCB either for a short period or long period on drugs metabolizing enzymes was studied. In addition, modulation of the effect of exposure to DCB on drug metabolism during thiamine deficiency and riboflavin deficiency were also investigated. Repeated exposure to DCB for a short-term in male Wistar rat increased the activity of a number of xenobiotic metabolizing enzymes including aminopyrine denethylase, aniline hydroxylase, DMN-demethylase I and II and GSH-S-transferase. The hepatic glutathione content was decreased after a single exposure to DCB. For a long period of exposure, all microsomal enzyme studied, i.e., aminopyrine demethylase, aniline hydroxylase and DMN-demethylase I and II were increased at 4 weeks of the treatment. With longer period of treatment, only DMN-demethylase activity remained above the normal level. The OSH-S-transferase activity was increased at 6 weeks and the hepatic glutathione content was decreased at 8 weeks of treatment. Exposure to DCB during nutritional deficiencies such as thiamine deficiency and riboflavin deficiency further potentiates the effect on certain enzymes. All microsomal enzymes investigated including aminopyrine demethylase, aniline hydroxylase, DMN-demethylase I and II and GSH-Stransferase were increased after repeated exposure to DCB both in the thiamine deficient and riboflavin deficient rats. DCB had no effect on the hepatic glutathione content in riboflavin deficient rats but reduced the content in thiamine deficient rats. Thiamine deficiency potentiates the effect of DCB only on DMN metabolism, while riboflavin deficiency potentiates the effect of DCB on DMN-demethylase I activity. Interestingly, the acute toxicity of DCB was increased by thiamine deficiency indicating that there are more susceptible to acute toxicity of the compound.ix, 84 leavesapplication/pdfengผลงานนี้เป็นลิขสิทธิ์ของมหาวิทยาลัยมหิดล ขอสงวนไว้สำหรับเพื่อการศึกษาเท่านั้น ต้องอ้างอิงแหล่งที่มา ห้ามดัดแปลงเนื้อหา และห้ามนำไปใช้เพื่อการค้าDrugs -- metabolismEnzyme activationRiboflavinRiboflavin DeficiencyThiamineThiamine DeficiencyVitamins -- toxicityMaster ThesisMahidol University