Changes in absorption and excretion of rhodamine 123 by sodium nitroprusside

Takizawa, Yusuke; Kitazato, Takuya; Ishizaka, Haruka; Kamiya, Naomi; Ito, Yasuhiko; Kishimoto, Hisanao; Tomita, Mikio; Hayashi, Masahiro

doi:10.1016/j.ijpharm.2013.04.026

Cited by 6 publications

(7 citation statements)

References 19 publications

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“…However, the results of this study indicated that piperine had a larger modulatory effect on paracellular permeation than on efflux inhibition across the nasal epithelial cells (although efflux inhibition was not explicitly ruled out as seen by the reduced efflux ratio value at the highest concentration). Since R123 is also able to diffuse paracellularly [26], the potential opening of tight junctions by the coapplied piperine correlated well with the increase in P app values of R123.…”

Section: Resultsmentioning

confidence: 64%

Capsaicin and Piperine as Functional Excipients for Improved Drug Delivery across Nasal Epithelial Models

et al. 2019

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The fruit from various pepper plants has been employed for the seasoning of food, as perfuming agents, and also as traditional medicines. Phytochemicals isolated from different pepper species have been found to modulate the pharmacokinetics of orally administered drugs. This study investigated the possibility to apply capsaicin and piperine (extracted alkaloids) as modulators for drug delivery across the nasal epithelium. Both a nasal epithelial cell line (RPMI 2650) and excised sheep nasal tissue were used as models to investigate the effects of the selected pepper compounds on drug permeation. FITC-dextran 4400 (MW 4400 Da) was used as a large molecular weight marker compound for paracellular transport, while rhodamine 123 was used as a marker compound that is a substrate for P-glycoprotein-mediated efflux. From the permeation results, it was clear that capsaicin inhibited P-glycoprotein efflux to a larger extent, while piperine showed drug permeation enhancement via other mechanisms. The cell cytotoxicity studies indicated that capsaicin was noncytotoxic up to a concentration of 200 µM and piperine up to a concentration of 500 µM as indicated by cell viability above 80%. The histological analysis of the excised nasal tissue and cultured RPMI 2650 cell layers indicated that some damage occurred after treatment with 200 µM capsaicin, but no changes were observed for piperine up to a concentration of 50 µM.

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Section: Resultsmentioning

confidence: 64%

Capsaicin and Piperine as Functional Excipients for Improved Drug Delivery across Nasal Epithelial Models

et al. 2019

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“…Intestinal barrier function as well as P‐gp function was evaluated by using in situ loop method as described previously with slight modification . Briefly, rats were placed on a heating pad to maintain the body temperature at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…Intestinal barrier function as well as P-gp function was evaluated by using in situ loop method as described previously with slight modification. 22 Briefly, rats were placed on a heating pad to maintain the body temperature at 37°C. The abdomen was opened by a midline longitudinal incision, and a 7-cm ileal segment was isolated and cannulated at both ends with plastic tubing.…”

Section: Simultaneous Determination Of Intestinal Barrier Function mentioning

confidence: 99%

Early downregulation of P‐glycoprotein facilitates bacterial attachment to intestinal epithelial cells and thereby triggers barrier dysfunction in a rodent model of total parenteral nutrition

et al. 2020

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Intestinal barrier dysfunction is a major complication of total parenteral nutrition (TPN). Our preliminary study revealed that intestinal P‐glycoprotein (P‐gp) was significantly downregulated under TPN treatment followed by disruption of barrier function, and thus the significance of early downregulation of P‐gp needs to be addressed. Herein, we report a pivotal role of P‐gp in the development of intestinal barrier dysfunction under TPN. Functional suppression of P‐gp may facilitate bacterial attachment to intestinal epithelial cells (IECs) and thereby induce degradation of tight junctions to trigger barrier dysfunction. By using a rat model of TPN, we found early downregulation of P‐gp function in ileum after 3‐day TPN, followed by disruption of barrier function after 7‐day TPN. By using Escherichia coli (E. coli) k88 and DH5α as type strains, we found significantly increased bacterial attachment to IECs in TPN group compared to sham. By using Caco‐2 cells as an IEC model in vitro, we found that functional suppression of P‐gp remarkably facilitated bacterial attachment to Caco‐2 cells, leading to subsequent disruption of intestinal barrier function. Of note, Occludin was significantly downregulated by bacterial attachment when P‐gp was functionally suppressed. Mechanistically, changes on Occludin were attributed to enhanced protein degradation instead of suppressed protein translation. Despite the half‐life of Occludin protein being unchanged by DH5α treatment alone, it was decreased by about 40% when P‐gp was simultaneously suppressed. Taken together, our findings revealed that early downregulation of intestinal P‐gp under TPN may be a potential therapeutic target to prevent the development of barrier dysfunction.

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“…Intestinal barrier function was evaluated using in situ loop method as described previously with slight modification. 25 Briefly, rats were placed on a heating pad to maintain the body temperature, and the abdomen was opened by a midline longitudinal incision. A 7-cm ileal segment was isolated with cannulation at both ends through plastic tubing.…”

Section: Evaluation Of Intestinal Barrier Function In Ileal Loopmentioning

confidence: 99%

Lin 28A/Occludin axis: An aberrantly activated pathway in intestinal epithelial cells leading to impaired barrier function under total parenteral nutrition

et al. 2020

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Disassembly of tight junctions is a major cause of intestinal barrier dysfunction under total parenteral nutrition (TPN), but the precise mechanisms have not been fully understood. Normally, RNA binding protein Lin 28A is highly restricted to embryonic stem cells and dramatically decreases as differentiation progresses; however, in our preliminary study it was found aberrantly increased in the intestinal epithelial cells of TPN rats, and thus its mechanism of action needs to be addressed. Herein, we report a pivotal role of Lin 28A in the regulation of tight junctions, which induces a sustained translational repression of Occludin, leading to disruption of intestinal barrier function under TPN. Using a rat model of TPN, we found time-dependent upregulation of Lin 28A, negatively correlated with Occludin. Using mouse intestinal organoids and human gut-derived Caco-2 cells as in vitro models, we found that expression of Occludin could be significantly suppressed by ectopic overexpression of Lin 28A.The underlying mechanisms may be partially attributed to translational repression, as the abundance of Occludin transcripts in polysomes was dramatically reduced by Lin 28A (polysomal profiling). Furthermore, Lin 28A was found to directly bind to Occludin mRNA 3′ untranslated coding region (UTR), thereby repressing the translation of Occludin transcripts through decapping enzyme 1A (DCP1a). Taken together, our findings revealed that Lin 28A/Occludin axis may be a novel mechanism accounting for the development of barrier dysfunction under TPN.

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Changes in absorption and excretion of rhodamine 123 by sodium nitroprusside

Cited by 6 publications

References 19 publications

Capsaicin and Piperine as Functional Excipients for Improved Drug Delivery across Nasal Epithelial Models

Capsaicin and Piperine as Functional Excipients for Improved Drug Delivery across Nasal Epithelial Models

Early downregulation of P‐glycoprotein facilitates bacterial attachment to intestinal epithelial cells and thereby triggers barrier dysfunction in a rodent model of total parenteral nutrition

Lin 28A/Occludin axis: An aberrantly activated pathway in intestinal epithelial cells leading to impaired barrier function under total parenteral nutrition

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