Abstract
Realgar and indigo naturalis are clinically combined to treat varieties of leukemia. Exploring the drug-drug interactions might be beneficial to find active substances and develop new targeted drugs. This study aimed at exploring the change of arsenic concentration in mice and across MDCK-MDR1 cells and the cytotoxicity on K562 cells when realgar and indigo naturalis were combined. In the presence or absence of indigo naturalis, pharmacokinetics and cell-based permeability assays were used to evaluate the change of arsenic concentration, and K562 cell line was applied to evaluate the change of cytotoxicity. The drug concentration-time profiles exhibited that the combination medication group generated higher AUC, thalf, and longer MRT for arsenic, compared with the single administration of realgar. The apparent permeability coefficients (Papp) of bidirectional transport in MDCK-MDR1 cell permeability experiments showed that arsenic permeability obviously went up when indigo naturalis was incubated together. The combination medication significantly decreased the cell viability of K562 cells when both the concentration of realgar and the concentration of indigo naturalis were nontoxic. The pharmacokinetic research, the MDCK-MDR1 based permeability study, and the K562 cytotoxicity study were united together to verify the combination medication of realgar and indigo naturalis enhanced the absorption and the permeability across cells for arsenic and effectively inhibited the proliferation of K562 cell line. The molecular binding of As4S4 and indirubin was analyzed by computational study. It is predicted that the formation of the complex [As4S4…Indirubin] involves noncovalent interaction that changes the concentration of arsenic.
Highlights
Arsenicals such as As2O3 and realgar (As4S4) have been used to treat hematological malignancy widely in both Eastern and Western world [1, 2]
The MDCK-MDR1 based permeability results were consistent with the pharmacokinetic study
The phenomenon which occurred in the pharmacokinetic study illustrated that the combination medication of realgar and indigo naturalis enhanced the arsenic AUC in blood
Summary
Arsenicals such as As2O3 and realgar (As4S4) have been used to treat hematological malignancy widely in both Eastern and Western world [1, 2]. One of the most famous arsenicals is the ATO injection (As2O3), Trisenox, which shows remarkable effect against APL after being approved by FDA [3]. Another famous arsenical is realgar, which has been proved to be as effective as arsenic trioxide with less irritation according to the clinical trials and treatments [4, 5]. Realgar and indigo naturalis are a common combination regimen therapeutically used in the treatment of different types of leukemia [8,9,10]. There are four main types of leukemia, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML), as well as a number of less common types [5, 6, 13, 14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Evidence-Based Complementary and Alternative Medicine
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
