Abstract:
P-glycoprotein (p-gp), a member of the superfamily ATP-binding cassette (ABC) is
known to be present in the absorptive enterocytes of the gastro-intestinal tract and
many other tissues in the body where it acts mainly as a defence mechanism against
exogenous assault. Defects in p-gp is speculated to result in the development of
diseases as mutations in genes are causes of numerous diseases in the metabolic
mosaic that underlies health. Due to the importance of p-gp, particularly in the
intestines, mutation of the gene encoding this protein may lead to the presence of
unusual compounds, xenobiotics in the body and the urine. It is thought that
defective p-gp in the intestine might also lead to the absorption of some metabolites
of bacterial origin and residue of digestion which normally would have been refluxed
back into the gut by the p-gp.
To investigate if defective p-gp may be involved in the manifestation of unusual
compounds and organic acids in the urine, inhibition of intestinal p-gp was proposed.
Grapefruit juice (GJ), a natural beverage commonly taken by the majority of the
populace has been reported to inhibit p-gp activity in the intestine (Spahn-Langguth & Langguth, 2001). Grapefruit juice was administered to healthy subjects in this study
and the sugars and organic acids content of the urine sample after administration was
analysed and compared with the controls (urine samples taken from the same set of
subjects before grapefruit juice administration). These were determined by thin layer
chromatography and gas chromatography-mass spectrophotometry respectively.
The thin layer chromatography revealed that there was no difference between the
concentrations of sugars in the control and samples after the administration of
grapefruit juice. This might indicate that the inhibition of p-gp or mutation of the gene
encoding p-gp does not result in the presence of sugars in the urine. The analysis of
organic acids by gas chromatography-mass spectrophotometry method showed a
remarkable difference between the organic acids present in the controls and urine
samples after the administration of grapefruit juice as well as their concentrations.
The organic acids solely from microbial origin were statistically analysed and the
results gave statistically significant increase in these organic acids in the adults.
There was no statistically significant increase in the children.
In conclusion, this study confirmed that grapefruit juice inhibits p-gp in the intestine
and this resulted in the presence of unusual organic acids from microbial origin in the
urine of the adults. The presence of some of these organic acids have been
indicated in some metabolic disorders and are also known to give rise to toxic effects
on brain, liver, muscle and other tissues. There is the need to do more study on p-gp
expression in children so that its functional roles and effect of the mutation of the
gene encoding this protein can be known.
