The effect of grapefruit juice, a P-glycoprotein inhibitor, on organic acid and conjugates urinary profile in healthy human subjects
Ogunrombi, Modupe Olufunmilayo
MetadataShow full item record
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.
- Health Sciences