Transient up-regulation of P-glycoprotein reduces tacrolimus absorption after ischemia–reperfusion injury in rat ileum

Omae, Takanori; Goto, Maki; Shimomura, Masahiro; Masuda, Satohiro; Ito, Kimitaka; Okuda, Masahiro; Inui, Ken Ichi

doi:10.1016/j.bcp.2004.10.016

Cited by 27 publications

(29 citation statements)

References 20 publications

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“…Indeed, Omae et al reported that alteration of P-gp expression aŠected the pharmacokinetics of tacrolimus. 13) We previously reported that the expression of P-gp after intestinal I/R following feeding was signiˆcantly altered in the ileum and kidney. 14) Although the expression of P-gp was not altered in the liver after intestinal I/R following feeding, mdr1a and mdr1b levels were altered.…”

Section: Introductionmentioning

confidence: 99%

Alteration of P-gp Expression after Intestinal Ischemia-reperfusion Following 16-h Fasting in Rats

et al. 2011

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Alteration of P-glycoprotein (P-gp) expression in‰uences the pharmacokinetics of P-gp substrates after intestinal ischemia-reperfusion (I/R). Fasting before intestinal I/R aŠects intestinal I/R injury. However, the eŠect of fasting on the alteration of P-gp expression after intestinal I/R has not been clariˆed. We previously reported that P-gp expression was altered after intestinal I/R following feeding. In the present study, we investigated the expression of P-gp after intestinal I/R following 16-h fasting. The mdr1a levels were decreased at 6 h in the jejunum, at 1 h in the ileum, at 6 and 24 h in the liver and at 6 h in the kidney. The mdr1b levels were decreased at 6 h in the ileum and at 1 and 6 h in the kidney. The mdr1b level in the liver was increased at 1 and 6 h. The expression of P-gp was decreased at 6 h in the jejunum, at 1, 6 and 24 h in the ileum, and at 6 h in the kidney. These alterations were diŠerent to those after intestinal I/R following feeding. In particular, the decrease in P-gp expression in the 16-h fasting I/R rats occurred at an early time during reperfusion compared with that in the feeding I/R rats. In conclusion, feeding condition aŠects the alteration of P-gp expression after intestinal I/R. Therefore, it is important to understand the patient's feeding condition for safe drug therapy.

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Section: Introductionmentioning

confidence: 99%

Alteration of P-gp Expression after Intestinal Ischemia-reperfusion Following 16-h Fasting in Rats

et al. 2011

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“…It is known that expression levels of ABC transporters are altered by intestinal I/R (9)(10)(11)(12)(13)(14). These alterations occur in the intestine, liver and kidney.…”

Section: Introductionmentioning

confidence: 99%

“…These alterations occur in the intestine, liver and kidney. Moreover, pharmacokinetics of several ABC transporter substrates are altered by intestinal I/R (9,12,13,15). However, there has been no report on alterations in expressions and transport activities of uptake transporters, including Oatps and Oats after intestinal I/R.…”

Section: Introductionmentioning

confidence: 99%

Intestinal Ischemia-Reperfusion Suppresses Biliary Excretion of Hepatic Organic Anion Transporting Polypeptides Substrate

Maruyama¹,

Ogura²,

Fujikawa³

et al. 2013

J Pharm Pharm Sci

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-Purpose. Intestinal ischemia-reperfusion (I/R) causes gut dysfunction and promotes multi-organ failure. The liver and kidney can be affected by multi-organ failure after intestinal I/R. Organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) are recognized in a broad spectrum from endogenous compounds to xenobiotics, including clinically important drugs. Therefore, it is important for understanding the pharmacokinetics to obtain evidence of alterations in OATPs and OATs expression and transport activities. In the present study, we investigated the expression of rat Oatps and Oats after intestinal I/R. Methods. We used intestinal ischemia-reperfusion (I/R) model rats. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Plasma concentration and biliary excretion of sulfobromophthalein (BSP), which is used as a model compound of organic anion drugs, were measured after intravenous administration in intestinal I/R rats. Results. Although Oat1 and Oat3 mRNA levels were not altered in the kidney, Oatp1a1, Oatp1b2 and Oatp2b1 mRNA levels in the liver were significantly decreased at 1-6 h after intestinal I/R. Moreover, Oatp1a1 and Oatp2b1 protein expression levels were decreased at 1 h after intestinal I/R. Plasma concentration of BSP, which is a typical substrate of Oatps, in intestinal I/R rats reperfused 1 h was increased than that in sham-operated rats. Moreover, the area under the concentration-time curve (AUC0-90) in intestinal I/R rats reperfused 1 h was significantly increased than that in sham-operated rats. The total clearance (CLtot) and the biliary clearance (CLbile) in intestinal I/R rats reperfused 1 h were significantly decreased than those in sham-operated rats. Conclusions. Oatp1a1 and Oatp2b1 expression levels are decreased by intestinal I/R. The decreases in these transporters cause alteration of pharmacokinetics of organic anion compound. The newly found influence of intestinal I/R on the expression and function of Oatps may be a key to perform appropriate drug therapy.

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“…5,6) It has been shown that the expression of transporters was altered in the organ after I/R. [7][8][9][10] I/R can occur in many organs, including intestine, liver and kidney. The intestine, liver and kidney play a principal role in the absorption and excretion of a wide variety of xenobiotics, including drugs and toxins, as well as endogenous compounds.…”

mentioning

confidence: 99%

“…7) However, the expression of other transporters in the small intestine has not been elucidated, and there has been no report on the expression of transporters in remote organs. BCRP plays role in prevention of intracellular accumulation of BCRP substrates in the body.…”

mentioning

confidence: 99%

Post-Transcriptional Regulation of Breast Cancer Resistance Protein after Intestinal Ischemia-Reperfusion

Ogura

Kobayashi

Itagaki

et al. 2008

Biological & Pharmaceutical Bulletin

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Breast cancer resistance protein (BCRP), the product of the ABCG2 gene, is a recently identified ATP binding cassette half-transporter. BCRP is expressed in a variety of tumor cells and many normal human tissues. In the small intestine, BCRP can limit the influx and facilitate the efflux to prevent intracellular accumulation of BCRP substrates. Ischemia-reperfusion (I/R) induces the release of reactive oxygen species, and organs are severely damaged by I/R. It has been shown that the expression of transporters was altered in the organ after I/R. The present study was undertaken to clarify the expression of BCRP after intestinal I/R. We showed that the expression level of Bcrp was significantly decreased at 1 h after I/R. Bcrp mRNA level was not altered at 1 h after I/R. These results suggest that Bcrp expression was regulated by a post-transcriptional regulation mechanism after intestinal I/R. Bcrp mRNA level was increased at 24 h after I/R, and the expression level of Bcrp protein was of the same level or slightly increased compared with sham operated-rats. Bcrp was slightly located at the intestinal membrane at 24 h after intestinal I/R. These results suggested that Bcrp was not translocated to the intestinal membrane after intestinal I/R. There is little information on post-transcriptional regulation compared with information on transcriptional regulation. In this study, it was shown that Bcrp expression is regulated by post-transcriptional regulation after intestinal I/R. These results of this study may provide important information for further studies aimed at revealing the biological function of Bcrp.

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Transient up-regulation of P-glycoprotein reduces tacrolimus absorption after ischemia–reperfusion injury in rat ileum

Cited by 27 publications

References 20 publications

Alteration of P-gp Expression after Intestinal Ischemia-reperfusion Following 16-h Fasting in Rats

Alteration of P-gp Expression after Intestinal Ischemia-reperfusion Following 16-h Fasting in Rats

Intestinal Ischemia-Reperfusion Suppresses Biliary Excretion of Hepatic Organic Anion Transporting Polypeptides Substrate

Post-Transcriptional Regulation of Breast Cancer Resistance Protein after Intestinal Ischemia-Reperfusion

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