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23
Figure legends
Figure 1. Uptake of [14C]TEA in HEK-hOCT2 and HEK-vector cells. HEK-hOCT2
(closed column) or HEK-vector (open column) cells were incubated with [14C]TEA (5 µM,
pH 7.4) for 2 min at 37°C. Each point represents the mean ± S.E. of three separate
experiments using three monolayers. ***: p < 0.001 compared with HEK-vector cells. When
the standard errors of the means are small, they are contained within the columns.
Figure 2. Time course of cisplatin uptake in HEK-hOCT2 cells. HEK-hOCT2 (closed
circles) or HEK-vector (open circles) cells were incubated with cisplatin (10 µM, pH 7.4) for
the specified duration (2, 15, 30, and 60 min) at 37°C. Each point represents the mean ± S.E.
of three separate experiments using three monolayers. **: p < 0.01, ***: p < 0.001 compared
with HEK-vector cells. When the standard errors of the means were small, error bars are
hidden behind the symbols.
Figure 3. Inhibition of LPZ and cimetidine on hOCT2-mediated transport of cisplatin.
HEK-hOCT2 cells were incubated at 37°C for 5 min with cisplatin (1 µM) in the absence or
presence of LPZ (100 µM) or cimetidine (100 µM). Each point represents the mean ± S.E. of
three separate experiments using three monolayers. ***: p < 0.001 compared with Control
(vehicle).
Figure 4. Time course of Pt uptake in rat renal slices. Renal slices were incubated with
cisplatin (50 µM, pH 7.5) at 25ºC (closed circles) and 4ºC (open circles) for the specified
duration (5, 10, and 20 min). Each point represents the mean ± S.E. of three separate
experiments using three slices. **: p < 0.01, ***: p < 0.001 compared with 4ºC. When the
standard deviation of the means were small, error bars are hidden behind the symbols.
24
Figure 5. Inhibition of LPZ and cimetidine on the uptake of Pt in rat renal slices. Renal
slices were incubated with cisplatin (50 µM, pH 7.5) at 25ºC for 5 min in the absence or
presence of LPZ (100 μM) or cimetidine (100 µM). Each point represents the mean ± S.E. of
three separate experiments using three slices. **: p < 0.01 compared with Control.
Figure 6. Effect of concomitant LPZ administration on renal Pt accumulation at 72 h
after cisplatin (7.5 mg/kg, i.p.) administration in rats. Each column represents the mean ±
S.D. of five rats. **: p < 0.01, ***: p < 0.001 compared with cisplatin rats.
Figure 7. Effect of concomitant LPZ (2 mg/kg) and cimetidine (20 mg/kg)
administration on the pharmacokinetics of Pt within 3 min after cisplatin (1 mg/kg)
intravenous administration in rats. (A) Plasma concentration-time profiles of Pt. (B) Renal
Pt accumulation. Each point and column represent the mean ± S.D. of five rats. *: p < 0.05, **:
p < 0.01 compared with Control (cisplatin only) rats. Control rats (open circles), Cisplatin +
LPZ rats (closed circles), and Cisplatin + Cimetidine rats (closed squares)
25
Table
Table 1. Renal functions in rats at 72 h after intraperitoneal administration cisplatin
Pcr (mg/dL)
Cisplatin + LPZ
Cisplatin + LPZ
(1 mg/kg)
(2 mg/kg)
Sham
Cisplatin
0.4 ± 0.0
1.3 ± 0.1***
1.1 ± 0.2 ***, #
0.8 ± 0.1 *** ,### ,††
4.0 ± 0.4
1.3 ± 0.2 ***
2.2 ± 0.3 ***, ##
2.8 ± 0.3 ***, ###, †
11 ± 1
97 ± 7 ***
51 ± 17 ***, ###
37 ± 9 **, ###
2.3 ± 1.3
76.4 ± 31.2 ***
2.9 ± 1.8 ###
2.6 ± 2.4 ###
CLcr
(mL/min/kg)
BUN (mg/dL)
Urinary L-FABP
(µg/g creatinine)
Results are mean ± S.D. of five rats. **: p < 0.01, ***: p < 0.001 compared with Sham rats, #: p
< 0.05,
##
: p < 0.01,
###
: p < 0.001 compared with Cisplatin rats, †: p < 0.05,
††
: p < 0.01
compared with Cisplatin + LPZ (1 mg/kg) rats.
BUN: blood urea nitrogen, CLcr: creatinine clearance, L-FABP: liver-type fatty acid binding
protein, LPZ: lansoprazole, Pcr: plasma creatinine
26
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