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Volume 56, Issue 6, Pages (December 1999)

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Presentation on theme: "Volume 56, Issue 6, Pages (December 1999)"— Presentation transcript:

1 Volume 56, Issue 6, Pages 2128-2136 (December 1999)
Role of organic anion transporter 1 (OAT1) in cephaloridine (CER)-induced nephrotoxicity  Michio Takeda, Akihiro Tojo, Takashi Sekine, Makoto Hosoyamada, Yoshikatsu Kanai, Hitoshi Endou  Kidney International  Volume 56, Issue 6, Pages (December 1999) DOI: /j x Copyright © 1999 International Society of Nephrology Terms and Conditions

2 Figure 1 Effect of probenecid (A) and cephaloridine (CER) (B) on para-aminohippuric acid (PAH) uptake in S3 rat organic anion transporter 1 (rOAT1). Each bar represents the mean ±SE for four experiments. *P < 0.05, **P < 0.01 and ***P < vs. control. Kidney International  , DOI: ( /j x) Copyright © 1999 International Society of Nephrology Terms and Conditions

3 Figure 2 Immunocytochemical staining illustrating rOAT1 expression in S3 rOAT1 and S3 pcDNA3.1 stained with antibody against rOAT1. (a) S3 rOAT1 (×450), (b) S3 pcDNA 3.1 (×450), (c) high magnification of longitudinal section of S3 rOAT1 (×1000), (d) immunoelectron micrograph of S3 rOAT1 (×6000). Kidney International  , DOI: ( /j x) Copyright © 1999 International Society of Nephrology Terms and Conditions

4 Figure 3 Cephaloridine (CER) uptake and efflux. (A) Uptake studies in S3 rOAT1 (□) and S3 pcDNA 3.1 (▪). (B) CER efflux from S3 rOAT1 preincubated with [14C]-CER. After 30 minutes incubation at 37°C with 50 μM [14C]-CER, the monolayers were incubated at 37°C in the absence (□) or presence (▪) of 1 mM CER. The amount of [14C]-CER within the supernatant was determined. Each bar represents the mean ±SE for four experiments. *P < 0.05 vs. control and **P < 0.01 vs. control. Kidney International  , DOI: ( /j x) Copyright © 1999 International Society of Nephrology Terms and Conditions

5 Figure 4 Effect of cephaloridine (CER) on the viability of S3 rOAT1 (▪) and S3 pcDNA3.1 (□). The cells were exposed to 0.5 mM (A) or 1.0 mM (B) CER for 6∼72 hours. Each bar represents the mean ±SE for four experiments. *P < 0.05 and **P < 0.01 vs. S3 pcDNA 3.1. Kidney International  , DOI: ( /j x) Copyright © 1999 International Society of Nephrology Terms and Conditions

6 Figure 5 Effect of probenecid and probucol on the viability of S3 rOAT1 exposed to 1 mM cephaloridine (CER) for 48 hours. Each bar represents the mean ±SE for four experiments. *P < 0.01 vs. control and **P < 0.05 vs. CER. Kidney International  , DOI: ( /j x) Copyright © 1999 International Society of Nephrology Terms and Conditions

7 Figure 6 Effect of cephaloridine (CER) on the amount of lipid peroxidation in S3 rOAT1 and S3 pcDNA3.1 in the absence or presence of probenecid or probucol. The cells were exposed to various concentrations of CER for 24 hours in the absence or presence of probenecid or probucol. Each bar represents the mean ±SE for five experiments. *P < 0.05 vs. control, **P < 0.01 vs. control and ***P < 0.05 vs. CER. Kidney International  , DOI: ( /j x) Copyright © 1999 International Society of Nephrology Terms and Conditions

8 Figure 7 Relationship between the effects of various cephalosporin antibiotics on PAH uptake by and viability of S3 rOAT1. Each bar represents the mean ±SE for four experiments. Symbols are: (1) CER, (2) cefadroxil, (3) cefotaxime, (4) cefamandole, (5) cefoperazone, (6) ceftriaxone, (7) cephalexin, (8) cephalothin, and (9) cefazolin (N = 4; r = 0.626; P < 0.05). Kidney International  , DOI: ( /j x) Copyright © 1999 International Society of Nephrology Terms and Conditions


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