1. Volume 73, Issue 11, Pages 1231-1239 (June 2008)
Hepatic cytochrome P450s metabolize aristolochic acid and reduce its kidney toxicity 
Y. Xiao, M. Ge, X. Xue, C. Wang, H. Wang, X. Wu, L. Li, L. Liu, X. Qi, Y. Zhang, Y. Li, H. Luo, T. Xie, J. Gu, J. Ren 
Kidney International 
Volume 73, Issue 11, Pages (June 2008)
DOI: /ki
Copyright © 2008 International Society of Nephrology Terms and Conditions

2. Figure 1
Survival rate in the WT, Null, and MC-pretreated wild-type (MC-WT) mice. Two-month-old male WT, Null, and MC-WT mice were observed for mortality within 14 days after a single injection of AAI at various doses. (a) 10 mg kg−1 AAI, n=10 in each group, (b) 20 mg kg−1 AAI, n=8 in each group, (c) 30 mg kg−1 AAI, n=8 in each group, the MC-WT group was pretreated with 60 mg kg−1 MC 24 h before the AAI injection.
Kidney International  , DOI: ( /ki )
Copyright © 2008 International Society of Nephrology Terms and Conditions

3. Figure 2
Comparison of AAI-induced kidney toxicity in the Null, WT, and MC-WT mice. All mice received a single intraperitoneal injection of AAI at 10 mg kg−1. (a–c) Body weight during 14 days after the treatment. Values presented are mean±s.d., n=5. **P<0.01 versus control mice. Histological examination of the kidney in AAI-treated Null (d), WT (e), and MC-WT (f) mice at 14 days (h and e stain, original magnifications × 200). (g) Representative kidney gross morphology in WT and Null mice at 14 days after the AAI treatment. (h) Serum BUN and (i) creatinine at 14 days. Values presented are mean±s.d., n=5. **P<0.01 versus control mice. ##P<0.01 versus WT mice.
Kidney International  , DOI: ( /ki )
Copyright © 2008 International Society of Nephrology Terms and Conditions

4. Figure 3
The serum levels of AAI in the Null, WT, and MC-WT mice. Two-month-old male mice received a single intraperitoneal injection of AAI at 10 mg kg−1 (a) and 20 mg kg−1 (b). Tail blood samples were collected from individual mice at nine time points after dosing, for determination of AAI concentrations, as described in Materials and Methods. Values presented are mean±s.d. n=6 for Null and WT mice, n=5 for MC-WT mice. **P<0.01 versus WT mice.
Kidney International  , DOI: ( /ki )
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5. Figure 4
The levels of AAI and its major metabolites in liver and kidney of the Null, WT, and MC-WT mice. The tissues were collected from 2-month-old male mice at 30 min after a single intraperitoneal injection of AAI at 10 or 20 mg kg−1. Tissues were processed for the determination of AAI, AAIa, and ALI as described in Materials and Methods. Typical HPLC chromatograms were obtained from the samples of mice treated with 20 mg kg−1 AAI (a, e). The AAI levels in liver and kidney (b, f). The AAIa levels in the liver and kidney (c, g). The ALI levels in liver and kidney (d, h). Quantity of the metabolites was expressed as the peak area (mAU·min) of the AAIa and ALI peak in the HPLC chromatogram. Values presented are mean±s.d. n=4, **P<0.01 versus WT mice. ND, not detected.
Kidney International  , DOI: ( /ki )
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6. Figure 5
Comparison of metabolic abilities of the microsomes isolated from liver of the Null, WT, and MC-WT mice. (a) Representative HPLC chromatograms were collected from the samples from the microsomal reactions with AAI. (b) Relative concentration of AAI after incubating with microsomes. (c) Quantity of AAIa formed after the incubation was expressed as the peak area (mAU·min) of the AAIa peak in the HPLC chromatogram. (d) Western blot analysis of microsomal preparations from the liver and kidney of the Null, WT, and MC-WT mice. The effect of MC on (e) CYP1A1 activity (EROD) and (f) CYP1A2 activity (MROD) in the liver and kidney microsomes from MC-WT and WT mice in reactions containing 1 mg ml−1 microsomal proteins and 10 μM 7-ethoxy- or 7-methoxyresorufin, and a NADPH generating system with an incubation at 37°C for 2 h. Values presented are mean±s.d. n=4, **P<0.01 versus WT mice.
Kidney International  , DOI: ( /ki )
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7. Figure 6
In vitro cytotoxicity assay for determining the toxic potency of AAI and ALI in human renal tubular epithelial cells (HK2). (a) Cell viability was determined in HK2 cells at 24 h after the treatment with AAI and ALI at concentrations of 25, 50, and 100 μM. **P<0.01 versus ALI-treated group. (b) The effect of S9 fraction treatment on AAI-induced cytotoxicity in HK2. Concentration of AAI and ALI in the culture was 50 μM. Values presented are mean±s.d., **P<0.01 versus AAI-treated group. The results are representative of three individual experiments.
Kidney International  , DOI: ( /ki )
Copyright © 2008 International Society of Nephrology Terms and Conditions