a-mice-model-of-chlorhexidine-gluconate-induced-peritoneal-damage

A Mice Model of Chlorhexidine Gluconate-Induced Peritoneal Damage

Peritoneal fibrosis is an important complication of peritoneal dialysis (PD). To investigate and address this problem, an appropriate animal model of PD ...

I-Shou University

Drug efflux transporters were highly related to the clinical drug resistance issues, such as cancer multi-drug resistance (MDR) and ocular drug resistance. In the present study, with the focus on human multi-drug resistance protein 1 (MRP1) and P-glycoprotein (P-gp), the inhibitory kinetics of polyoxyethylene (20) sorbitan monooleate (Tween 80) on both drug binding sites and ATPase were in-depth evaluated. We used the stable-cloned ABCB1/Flp-In™-293 and ABCC1/Flp-In™-293 cell lines, and inside-out membrane vesicles for underlying mechanisms investigation while used the drug induced cancer MDR cell line KB/VIN and human retinal pigmented epithelium cell line ARPE-19 for efficacy evaluation. Results showed that Tween 80 exhibited non-competitive inhibition on the doxorubicin efflux of P-gp and MRP1, with the inhibitory affinity 0.00195% (14.89 μM) and 0.00245% (18.7 μM), respectively. Tween 80 inhibited the basal ATPase activity of P-gp and MRP1 in a dose-dependent manner (0.0002-0.02%) and demonstrated significant reversing effects on the doxorubicin, paclitaxel, and vincristine resistance at the concentration of 0.001% (7.63 μM). This was the first thorough study revealing the interactions between Tween 80 and P-gp or MRP1 at a molecular level and these findings suggested that Tween 80 was a potential candidate for future combinatorial regimens applied in the "drug resistance" issue.

Repositioning application of polyoxyethylene (20) sorbitan monooleate on ocular drug resistance and cancer multi-drug resistance by inhibiting the ATPase activity of human multidrug resistance protein 1 and P-glycoprotein.

Li-Hung Chen

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