Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1.
This study was performed to elucidate the possible involvement of organic anion transporter 3 (OAT3) in cephaloridine (CER)-induced nephrotoxicity and compare the substrate specificity between rOAT3 and rat OAT1 (rOAT1) for various cephalosporin antibiotics, using proximal tubule cells stably expressing rOAT3 (S2 rOAT3) and rOAT1 (S2 rOAT1). S2 rOAT3 exhibited a CER uptake and a higher susceptibility to CER cytotoxicity than did mock, which was recovered by probenecid. Various cephalosporin antibiotics significantly inhibited both estrone sulfate uptake in S2 rOAT3 and para-aminohippuric acid uptake in S2 rOAT1. The Ki values of CER, cefoperazone, cephalothin and cefazolin for rOAT3- and rOAT1-mediated organic anion transport ranged from 0.048 to 1.14 mM and from 0.48 to 1.32 mM, respectively. These results suggest that rOAT3, at least in part, mediates CER uptake and CER-induced nephrotoxicity as rOAT1. There was some difference of affinity between rOAT3 and rOAT1 for cephalosporin antibiotics.
Jung
Kyu Yong
KY
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka-shi, Tokyo, Japan. endouh@kyorin-u.ac.jp
Takeda
Michio
M
Shimoda
Minoru
M
Narikawa
Shinichi
S
Tojo
Akihiro
A
Kim
Do Kyung
DK
Chairoungdua
Arthit
A
Choi
Bong Kyu
BK
Kusuhara
Hiroyuki
H
Sugiyama
Yuichi
Y
Sekine
Takashi
T
Endou
Hitoshi
H
D000818:Animals; D002509:Cephaloridine / Q000633:toxicity*; D002511:Cephalosporins / Q000633:toxicity*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects*; D051379:Mice; D029362:Organic Anion Transporters, Sodium-Independent / Q000032:analysis / Q000502:physiology*; D051381:Rats
D002511:Cephalosporins; D029362:Organic Anion Transporters, Sodium-Independent; C421102:Slco1a1 protein, rat; C421143:Slco1a5 protein, rat; D002509:Cephaloridine