Factors influencing the intestinal absorption and metabolism of polynuclear aromatic hydrocarbons

Rahman, Anisur (1986) Factors influencing the intestinal absorption and metabolism of polynuclear aromatic hydrocarbons. Masters thesis, Memorial University of Newfoundland.

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Abstract

In this study various factors governing the intestinal absorption and metabolism of polynuclear aromatic hydrocarbons (PAHs) were examined. -- In the first part, the effects of gastrointestinal hormones and post-resection intestinal adaptive hypertrophy on xenobiotic-metabolizing enzymes, benzo(a)pyrene hydroxylase (BPH) and UDP-glucuronyl transferase (UDP-GT) were observed. Fasted rats were injected with either saline, 250 μg/kg pentagastrin, 20 μg/kg cholecystokinin-octapeptide (CCK-OP) or 75 units/kg secretin daily for three days and killed on the fourth day. Microsomal preparations were made from the intestinal mucosa and used in the enzyme assays. Pentagastrin produced a 236% increase in BPH activity in colonic mucosa but the rest of the intestinal segments remained unaffected. CCK and secretin did not cause any change in BPH activity in the intestine. UDP-GT activity in all parts of the rat intestine was unaffected by the hormonal treatment. It is concluded that under the present experimental situation only pentagastrin has a significant effect on BPH activity in the colon. -- Fasted rats were killed 4 weeks after a 70-cm resection of proximal intestine. Remaining ileal segments were thickened and increased in diameter. The mean villous height in the remnant ileum was l77% and 130% greater than the villous height in the control ileum and jejunum, respectively. The total protein content in the remnant ileum also increased. UDP-GT activity per mg of protein showed a statistically significant drop in the remnant ileal mucosa but the BPH activity remained unchanged. It is proposed that the presumably less mature hyperplastic cells have diminished UDP-GT activity. The unchanged BPH activity remains unexplained. -- In the second half of this study, factors influencing the bioavailability of PAHs from the intestinal content were observed. -- Rats with biliary and duodenal fistulae were administered radiolabelled hydrocarbons - 2,6-dimethylnaphthalene, phenanthrene, 7,12-dimethylbenzanthracene, anthracene and benzo(a)pyrene - dissolved in corn oil only or corn oil with exogenous bile. Subsequent 24-hour biliary and urinary excretion of radiolabel was monitored to assess the efficiency of absorption with and without bile. The following values for absorption without bile (as a % of absorption with bile) were obtained : 2,6-DMN-91.6%, phenanthrene-96.7%, anthracene-70.8%, 7,12-DMBA-43.4% and BP-22.9%. The values for anthracene, 7,12-DMBA and BP were significantly less than 100% but the values for 2,6-DMN and phenanthrene were not. Since the water solubility of the structural isomers phenanthrene and anthracene are 1.29 mg/L and 0.073 mg/L respectively, it is proposed here that for these PAHs, a water solubility of approximately less than 1 mg/L, makes the presence of duodenal bile a prerequisite for efficient absorption. -- In continuation of the studies with the PAHs, it was established in the last part of this study that the bioavailability of 2,6-DMN from the intestinal content was not affected by the nature of the dietary vehicle (lipid or non-lipid vehicle) and concomitant fat digestion and absorption. Also, the biliary metabolites of 2,6-DMN undergo an efficient enterohepatic circulation. -- [KEYWORDS]: Anthracene; Benzo(a)pyrene(BP); Benzo(a)pyrene Hydroxylase (BPH); Cholecystokinin; 7,12-Dimethylbenzanthracene (DMBA); 2,6-Dimethylnaphthalene (DMN); Intestinal resection and PAHs metabolism; Pentagastrin; Phenanthrene; Polynuclear Aromatic Hydrocarbons (PAHs); Secretin; UDP-Glucuronyl transferase (UDP-GT)

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