Screening of allergic components mediated by H(1)R in homoharringtonine injection through H(1)R/CMC-HPLC/MS.
It has been reported that the histamine H1 receptor (H(1)R) gene is up-regulated in patients with allergic rhinitis and H(1)R expression level strongly correlates with the severity of allergy symptoms. Drugs for therapy should avoid allergy symptoms, especially for patients with over-expressed H(1)R. Therefore, screening of the components which could induce H(1)R activation is urgently needed for drug safety evaluation. Homoharringtonine injection is a preparation for acute nonlymphocytic leukemia, which is approved by China Food and Drug Administration (CFDA) and US Food and Drug Administration. However, severely adverse reactions often occur with intravenous injection of the preparation. In present study, an H(1)R/CMC model was applied for capturing membrane retained components which could induce H(1)R activation. Retention components were enriched and analyzed by H(1)R/CMC-HPLC/MS. Homoharringtonine was recognized, separated and identified in homoharringtonine injection. Ca(2+) flux assay and p-IP3R expression founded that homoharringtonine retained by the H1 R/CMC model increased phosphorylation of IP3R and promoted cytosolic free Ca(2+) elevation in a dose-dependent manner which further verified the activity of homoharringtonine in activating the H1 R. In conclusion, homoharringtonine was screened and identified as a potential allergic factor. This provides an indication that a patient with over-expressed H1 R should be aware of possible allergic reaction when applying homoharringtonine injection.
School of Medicine, Xi'an Jiaotong University, 76#, Yantan Westroad, Xi'an, 710061, China.
Ying
Y
Guo
Shengli
S
Han
Jingjing
J
Cao
Qi
Q
Liu
Tao
T
Zhang
D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D004342:Drug Hypersensitivity / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006248:Harringtonines / Q000009:adverse effects* / Q000276:immunology* / Q000378:metabolism; D000077863:Homoharringtonine; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D010766:Phosphorylation / Q000187:drug effects; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D006248:Harringtonines; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011969:Receptors, Histamine H1; D011994:Recombinant Proteins; D000077863:Homoharringtonine; D002118:Calcium
Ca2+ flux; cell membrane chromatography; herbal medicine injection; histamine H1 receptor; homoharringtonine