Detoxification in relation to toxin tolerance in desert woodrats eating creosote bush.

We studied the relationship between the use of three detoxification pathways and urine pH and the tolerance of desert woodrats from two populations to a mixture of naturally occurring plant secondary metabolites (mostly phenolics) in resin from creosote bush (Larrea tridentata). The two populations of desert woodrats came from the Mojave desert (Mojave woodrats), where woodrats consume creosote bush, and from the Great Basin desert (Great Basin woodrats), where the plant species is absent. We fed woodrats alfalfa pellets containing increasing levels of the phenolic resin and measured three detoxification pathways and urine pH that are related to detoxification of allelochemicals. We found that the excretion rate of two phase II detoxification conjugates, glucuronides and sulfides. increased with increasing resin intake, whereas excretion of hippuric acid was independent of resin intake, although it differed between populations. Urine pH declined with increasing resin ingestion. The molar proportion of glucuronides in urine was three times that of the other conjugates combined. Based on an evaluation of variation in the three detoxification pathways and urine pH in relation to resin intake, we rejected the hypotheses that woodrats' tolerance to resin intake is related to capacity for amination, sulfation, or pH regulation. However, Mojave woodrats had higher maximum glucuronide excretion rates, and we accepted the hypothesis that within and between populations woodrats tolerate more resin because they have a greater capacity for glucuronide excretion.

Dietary regulation of intestinal ascorbate uptake in guinea pigs.

We measured ascorbic acid (AA) uptake across the intestinal brush border in vitro in intact tissue from guinea pigs fed maintenance AA (200 mg/kg diet) or made hypervitaminotic (5,000 mg/kg diet) or hypovitaminotic (chronically and acutely). Total uptake per centimeter ileum was 25-50% lower in hypervitaminotic juvenile, adult male, and lactating guinea pigs compared with their respective controls, whereas carrier-mediated D-glucose uptake and Na(+)-independent AA uptake were similar. High dietary ascorbate specifically reduced the Vmax for carrier-mediated AA uptake. Hypovitaminosis had no significant effect on uptake of AA or other solutes. We performed diet-switching experiments (high-AA diet to maintenance diet) with young and adult guinea pigs to determine the reversibility of the downregulation. In adult guinea pigs, the downregulation of AA uptake was reversible within 7 days. In the young of mothers fed high AA during pregnancy and lactation, and which fed on high AA for 14 days after weaning, the downregulation was reversible within 14 days. Thus regulation of AA uptake is reversible and therefore probably does not play a significant role in the development of vitamin C dependency in human adults, or their young, after ingestion of megadoses of ascorbic acid.