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Age and sex differences in expression of P-glycoprotein (P-gp/Mdr1/Abcb1) in rat liver and kidneys

P-glycoprotein (P-gp ; ABCB1 in humans/Abcb1 in rodents) is an ATP-dependent multidrug efflux transporter in the cell membrane, also known as the multidrug resistant protein 1 (MDR1 in humans/Mdr1 in animals), constitutively expressed in the a) bile canaliculi of hepatocytes, b) brush-border membrane of the renal proximal tubule cells, c)luminal membrane of the intestinal enterocytes, d) blood-brain, blood-testis, and mother-foetus barriers, and e) hematopoietic cells. P-gp mediates the transport of some endogenous compounds and various xenobiotics (drugs, toxins, environmental organic compounds, and their metabolites) out of the cells, thus protecting the cell’s interior from the potentially toxic effects of these compounds. Although P-gp is a highly studied transporter in a variety of(patho)physiological conditions in human and animal organs, its age-dependent expression is still a controversial issue. Here, we investigated the ontogenic pattern of P-gp protein expression in rat liver and kidneys to provide insight into the drug transport capacity in these organs at different ages. P-gp protein expression was studied by immunocytochemistry and Western blotting in organs from neonatal (age, 1 day), prepubertal (age, 3 weeks), adult(age, 3 months), and old (age, 2 years) male and female Wistar rats. In both sexes, the liver P-gp expression pattern was: neonatal (highest) > prepubertal > adult < old. In the kidneys, the P-gp expression exhibited the pattern: neonatal < prepubertal < adult (highest) > old. Better knowledge of the ontogeny of P-gp expression may improve experimental design and the interpretation of results of toxicity studies in juvenile animals as well as the understanding of drug toxicity in different age groups in translational studies.

age differences; immunocytochemistry; kidney; liver; Mdr1; proximal tubule; P-gp; Western blotting

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