Effect of the drilling fluids ipar and neodene on biotransforming enzymes in rats

Wang, Hui (2000) Effect of the drilling fluids ipar and neodene on biotransforming enzymes in rats. Masters thesis, Memorial University of Newfoundland.

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Abstract

Drilling fluid, as a rich source of petroleum compounds, is a potential environmental pollutant after disposal. The effects of two drilling fluids: IPAR and NEODENE on biotransforming enzyme activities in rats were examined following administration of 1 to 4 doses (i.p. 1ml/dose). These activities measured included hepatic and renal mixed function oxidases, glutathione S-transferases, and peroxisomal enzymes. -- IPAR specifically induced two isoforms of cytochrome P450: CYP 1A1 and CYP2B1 in liver. Induction of CYP 1A1 protein (100%) as well as its associated EROD activity (46%) was significant 24 hours after IPAR administration. Although these elevations returned to normal by 72 hours, further administration of IPAR caused EROD activity and CYP 1A1 protein levels to increase by about 30% in both the 2 dose and 4 dose treatment groups. Moreover, IPAR increased hepatic PROD activity (CYP 2B1 associated) 9-fold in the 24 hour (1 dose) group, 3-fold in the 72 hour (1 dose) and 6 day (2 doses) groups, and 1.5-4 fold in the 12 day (4 doses) group. The associated CYP 2B1 protein levels were also increased correspondingly, but the extent of increase was not as much as that of PROD activity. However, IPAR had no effect on glutathione S-transferases activities. -- In contrast, NEODENE significantly inhibited hepatic microsomal cytochrome P450 levels (25 to 30%) and the dependent EROD activity (20 to 45%), along with glutathione S-transferase activity (DCNB substrate, 14 to 40%) in all four treated groups. However, Western blot analysis showed that individual protein levels did not correlate well with the associated enzyme activity. The CYP 1A1 protein concentration was slightly increased as opposed to the decreased EROD activity. The Ya protein of glutathione S-transferase was decreased only in the 12 day (4 doses) group and remained unchanged in other treated groups. The Yb subunit of glatathione S-transferase was not altered corresponding to the decreased GST activity. There was no change in PROD activity after NEODENE administration. -- Overall, IPAR and NEODENE have the potential to cause metabolic dysfunction. A significant weight loss was observed after NEODENE administration in every treated group. The inhibition of xenobiotic metabolizing enzyme activities would lead to a slower elimination of NEODENE which may contribute to its toxicity. However, the alteration of enzyme activity is not dose-dependent. Therefore, these endpoints as biomarkers of drilling fluid exposure need to be further examined. -- The peroxisomal enzymes, palmitoyl CoA oxidase and carnitine transferase along with microsomal lauric acid hydroxylase and serum cholesterol and triglycerides levels were not significantly altered suggesting that neither IPAR nor NEODENE is likely to cause peroxisomal proliferation. -- Overall, it appears that both IPAR and NEODENE have significant effects on biotransforming enzymes and NEODENE appears to be more toxic than IPAR.

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