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Molecules 2016, 21(1), 46; doi:10.3390/molecules21010046

The Alterations in the Expression and Function of P-Glycoprotein in Vitamin A-Deficient Rats as well as the Effect of Drug Disposition in Vivo

1
The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China
2
The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 17 November 2015 / Revised: 22 December 2015 / Accepted: 23 December 2015 / Published: 29 December 2015
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [1048 KB, uploaded 29 December 2015]   |  

Abstract

This study was aimed to investigate whether vitamin A deficiency could alter P-GP expression and function in tissues of rats and whether such effects affected the drug distribution in vivo of vitamin A-deficient rats. We induced vitamin A-deficient rats by giving them a vitamin A-free diet for 12 weeks. Then, Abcb1/P-GP expression was evaluated by qRT-PCR and Western blot. qRT-PCR analysis revealed that Abcb1a mRNA levels were increased in hippocampus and liver. In kidney, it only showed an upward trend. Abcb1b mRNA levels were increased in hippocampus, but decreased in cerebral cortex, liver and kidney. Western blot results were in good accordance with the alterations of Abcb1b mRNA levels. P-GP function was investigated through tissue distribution and body fluid excretion of rhodamine 123 (Rho123), and the results proclaimed that P-GP activities were also in good accordance with P-GP expression in cerebral cortex, liver and kidney. The change of drug distribution was also investigated through the tissue distribution of vincristine, and the results showed a significantly upward trend in all indicated tissues of vitamin A-deficient rats. In conclusion, vitamin A deficiency may alter Abcb1/P-GP expression and function in rat tissues, and the alterations may increase drug activity/toxicity through the increase of tissue accumulation. View Full-Text
Keywords: vitamin A deficiency; P-glycoprotein; rhodamine 123; vincristine vitamin A deficiency; P-glycoprotein; rhodamine 123; vincristine
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Wang, Y.; Qin, H.; Zhang, C.; Huan, F.; Yan, T.; Zhang, L. The Alterations in the Expression and Function of P-Glycoprotein in Vitamin A-Deficient Rats as well as the Effect of Drug Disposition in Vivo. Molecules 2016, 21, 46.

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