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. 2012:2012:412736.
doi: 10.1155/2012/412736. Epub 2012 Jul 11.

In Vitro and In Vivo Genotoxicity Assessment of Aristolochia manshuriensis Kom

Youn-Hwan Hwang  1 , Taesoo Kim, Won-Kyung Cho, Hye Jin Yang, Dong Hoon Kwak, Hyunil Ha, Kwang Hoon Song, Jin Yeul Ma
Affiliations

In Vitro and In Vivo Genotoxicity Assessment of Aristolochia manshuriensis Kom

Youn-Hwan Hwang et al. Evid Based Complement Alternat Med. 2012.

Abstract

Arisolochiae species plants containing aristolochic acids I and II (AA I and AA II) are well known to cause aristolochic acid nephropathy (AAN). Recently, there are various approaches to use AAs-containing herbs after the removal of their toxic factors. However, there is little information about genotoxicity of Arisolochiae manshuriensis Kom. (AMK) per se. To obtain safety information for AMK, its genotoxicity was evaluated in accordance with OECD guideline. To evaluate genotoxicity of AMK, we tested bacterial reverse mutation assay, chromosomal aberration test, and micronucleus test. Here, we also determined the amounts of AA I and II in AMK (2.85 ± 0.08 and 0.50 ± 0.02 mg/g extract, resp.). In bacterial reverse mutation assay, AMK dose-dependently increased revertant colony numbers in TA98, TA100 and TA1537 regardless of metabolic activation. AMK increased the incidence of chromosomal aberration in Chinese hamster ovary-K1 cells, but there was no statistically significant difference. The incidences of micronucleus in bone marrow erythrocyte were significantly increased in mice after oral administration of AMK (5000 mg/kg), comparing with those of vehicle group (P < 0.05). The results of three standard tests suggest that the genotoxicity of AMK is directly related to the AAs contents in AMK.

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Figures

Figure 1
Figure 1
Chemical structure of aristolochic acid I (R=OCH3) and II (R=H).
Figure 2
Figure 2
HPLC chromatogram of Aristolochiae manshuriensis Kom. (AMK) at 240 nm. (a) Aristolochic acid I (AA I, 38.263 min) and aristolochic acid II (AA II, 36.804 min); (b) amount of AA I (2.85 ± 0.08 mg/g extract) and AA II (0.50 ± 0.02 mg/g extract) in AMK.
Figure 3
Figure 3
Effect of Aristolochiae manshuriensis Kom. (AMK) on bacterial reverse mutation in the presence (+S9) or absence (−S9) of rat liver S9 mix. (−), vehicle control; (+), positive control.
Figure 4
Figure 4
Effect of Aristolochiae manshuriensis Kom. (AMK, 0, 1250, 2500, and 5000 mg/kg body weight, oral administration) on the incidence (%) of micronucleated polychromatic erythrocyte (MNPCE, histogram bar, left Y-axis) and the PCE/NCE (polychromatic/normochromatic erythrocyte) ratio (curve with dot, right Y-axis) in preliminary ((a), n = 3) and main study ((b), n = 6). (−), vehicle control; (+), positive control (mitomycin C, MMC, 2 mg/kg). Asterisks denote statistically differences (*P < 0.05, **P < 0.01).
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