RT Journal Article
SR Electronic
T1 Structural Changes in Albumin Are a Possible Mechanism for Fluctuation of Cefazorin and Ibuprofen Plasma Protein Binding in Rats with Carcinogen-induced Osteosarcoma
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2063
OP 2069
VO 35
IS 4
A1 YUKARI ITAKURA
A1 SHINO TAGA
A1 CHIEKO IWATA
A1 HITOMI TERAMACHI
A1 KEN-ICHI MIYAMOTO
A1 HIROYUKI TSUCHIYA
A1 TAKASHI WADA
A1 RYO MATSUSHITA
YR 2015
UL http://ar.iiarjournals.org/content/35/4/2063.abstract
AB Background/Aim: It is known that the protein-unbound fraction (fp) of warfarin fluctuates in the plasma of cancer patients and the fluctuation of fp is correlated with albumin concentration. However, this mechanism remains unclear. The present study was performed with the objective of elucidating variations in the protein-binding rate of specific drugs in the presence of cancer, as well as the mechanisms involved. Materials and Methods: Experiments were performed using Fisher 344 model rats, that we have used in previous studies. A single i.v. injection of cefazolin (CEZ) 20 mg/kg or ibuprofen (IB) 10 mg/kg was administered to both tumor-bearing and control groups. We compared relevant pharmacokinetics. Purified albumin was checked for purity with SDS-PAGE and was used in experiments on protein binding of CEZ and IB. Results: The fp of CEZ in plasma from the tumor-bearing group increased approximately 2.9-fold and the fp of IB also increased about 2.7-fold. For that reason, we purified albumin from plasma and examined its spectroscopic signature. We showed that conformational changes (i.e., decreases in the hydrophobic region, increases in endogenous tryptophan fluorescence intensity and decrease in α-helical content) had occurred in albumin in the tumor-bearing group. Conclusion: In the present study, we confirmed that, in a state of cancer morbidity, fp was elevated for site I high-affinity CEZ and site II high-affinity IB. Moreover, our findings indicated that, as a cause of those elevations, a decrease in the albumin concentration and conformational changes due to an oxidation are involved.