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
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 we...
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MDPI AG
2015-12-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/1/46 |
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| author | Yubang Wang Heng Qin Chengxiang Zhang Fei Huan Ting Yan Lulu Zhang |
| author_facet | Yubang Wang Heng Qin Chengxiang Zhang Fei Huan Ting Yan Lulu Zhang |
| author_sort | Yubang Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T21:32:47Z |
| format | Article |
| id | doaj.art-017c9bd9014b4257a8de185fd88aa6c2 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T21:32:47Z |
| publishDate | 2015-12-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-017c9bd9014b4257a8de185fd88aa6c22022-12-22T00:50:07ZengMDPI AGMolecules1420-30492015-12-012114610.3390/molecules21010046molecules21010046The Alterations in the Expression and Function of P-Glycoprotein in Vitamin A-Deficient Rats as well as the Effect of Drug Disposition in VivoYubang Wang0Heng Qin1Chengxiang Zhang2Fei Huan3Ting Yan4Lulu Zhang5The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, ChinaThe Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, ChinaThe Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, ChinaThe Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, ChinaThe Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, ChinaThe Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, ChinaThis 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.http://www.mdpi.com/1420-3049/21/1/46vitamin A deficiencyP-glycoproteinrhodamine 123vincristine |
| spellingShingle | Yubang Wang Heng Qin Chengxiang Zhang Fei Huan Ting Yan Lulu Zhang 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 vitamin A deficiency P-glycoprotein rhodamine 123 vincristine |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | alterations in the expression and function of p glycoprotein in vitamin a deficient rats as well as the effect of drug disposition in vivo |
| topic | vitamin A deficiency P-glycoprotein rhodamine 123 vincristine |
| url | http://www.mdpi.com/1420-3049/21/1/46 |
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