Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs

Jl, Vanherweghem; Tielemans, Christian; Abramowicz, Daniel; Depierreux, Michel; Vanhaelen-Fastré, Renée; Vanhaelen, Maurice; Dratwa, Max; Richard, C.; Vandervelde, Dominique; Verbeelen, D.; Jadoul, Michel

doi:10.1016/0140-6736(93)92984-2

Cited by 978 publications

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“…Likewise, highly significant correlations were found between the 7-ethoxyresorufin O-deethylase activities and the levels of individual AAI-DNA adducts (r 1 ϭ 0.904, p Ͻ 0.005 for dG-AAI; r 1 ϭ 0.895, p Ͻ 0.005 for dA-AAI; r 1 ϭ 0.921, p Ͻ 0.001 for dA-AAII). The correlations were calculated with data Numbers are averages Ϯ SEM (n ϭ 4) of duplicate in vitro incubations; each DNA sample was determined by 2 postlabeled analyses.- 1 The detection limit of RAL was 0.1/10 9 nucleotides.-2 Concentrations of NADH and NADPH were 1 mM.-3 Concentrations of arachidonic acid was 0.1 mM. …”

Section: Correlation Of Cyp-and Nadph:cyp Reductase-linked Enzyme Actmentioning

confidence: 99%

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Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:Cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid‐DNA adducts found in patients with urothelial cancer

Stiborová

Frei

Hodek

et al. 2004

Intl Journal of Cancer

135

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Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, has been associated with the development of urothelial cancer in humans. Understanding which human enzymes are involved in AA activation and/or detoxication is important in the assessment of an individual's susceptibility to this plant carcinogen. Using the 32 P postlabeling assay, we examined the ability of microsomal samples from 8 human livers and from 1 human kidney to activate AAI, the major component of the plant extract AA, to metabolites forming adducts in DNA. Microsomes of both organs generated DNA adduct patterns reproducing those found in renal tissues from humans exposed to AA. 7-(deoxyadenosin-N 6 -yl)aristolactam I, 7-(deoxyguanosin-N 2 -yl)aristolactam I and 7-(deoxyadenosin-N 6 -yl)aristolactam II were identified as AA-DNA adducts formed from AAI by all human hepatic and renal microsomes. To define the role of human microsomal enzymes in the activation of AAI, we investigated the modulation of AAI-DNA adduct formation by cofactors and selective inhibitors of microsomal reductases, cytochrome P450 (CYP) enzymes, NADPH:CYP reductase and NADH:cytochrome b 5 reductase. We also determined whether the activities of CYP and NADPH:CYP reductase in different human hepatic microsomal samples correlated with the levels of AAI-DNA adducts formed by the same microsomal samples. On the basis of these studies, we attribute most of the activation of AAI in human hepatic microsomes to CYP1A2. In contrast to human hepatic microsomes, in human renal microsomes NADPH:CYP reductase is more effective in AAI activation. In addition, prostaglandin H synthase is another enzyme activating AAI in renal microsomes. The results demonstrate for the first time the potential of microsomal enzymes in human liver and kidney to activate AAI by nitroreduction.

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Section: Correlation Of Cyp-and Nadph:cyp Reductase-linked Enzyme Actmentioning

confidence: 99%

“…1,2 About 100 cases have been identified so far in Belgium, half of which needed renal replacement therapy, mostly including renal transplantation. [3][4][5] The observed nephrotoxicity has been traced to the ingestion of Aristolochia fangchi containing carcinogenic and nephrotoxic aristolochic acid (AA) inadvertently included in slimming pills.…”

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confidence: 99%

Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:Cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid‐DNA adducts found in patients with urothelial cancer

Stiborová

Frei

Hodek

et al. 2004

Intl Journal of Cancer

135

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“…It was suggested that S. tetrandra was inadvertently replaced by A. fangchi. Thin-layer chromatography detection of AAs in these herbal preparations failed however [19]. Afterwards AAs were found in 11 of the 12 batches of S. tetrandra powder delivered to Belgian pharmacies during the treatment period [20].…”

Section: Introductionmentioning

confidence: 99%

Enforcement of the ban on aristolochic acids in Chinese traditional herbal preparations on the Dutch market

et al. 2007

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In traditional chinese medicine several Aristolochia species are used. Aristolochia spp. contain a mixture of aristolochic acids (AAs), mainly AA I and AA II which are nephrotoxicants and carcinogens. After AA-related nephropathy (AAN) and urothelial cancer were described in female patients in Belgium following intake of AA-contaminated herbal preparations, herbs with AAs were prohibited worldwide. Confusing nomenclature can cause AA contamination of certain Chinese traditional herbal preparations (THPs). Here we report the results of investigations by the Dutch Food and Consumer Product Safety Authority (VWA) into the presence of AAs in THPs sampled on the Dutch market using a liquid-chromatography--mass spectrometry method. Between 2002 and 2006 we sampled 190 Chinese THPs using recent information on Chinese THPs potentially containing AAs. AA I was found in 25 samples up to a concentration of 1,676 mg/kg. AA II was also found in 13 of these samples up to 444 mg/kg. All 25 positive samples including Mu Tong, Fang Ji, Tian Xian Teng and Xi Xin were part of a group of 68 THPs identified as possibly containing AAs. In a worst-case scenario, use of a sample of Mu Tong with the highest AA content over a 7-day period would result in the same intake levels of AAs which significantly raised the cancer risk in the Belgian AAN cases. Our results show that contaminated THPs still can be found on the market following worldwide publicity. Therefore, it can be concluded that testing of possibly AAcontaminated THPs is still essential.

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“…Half of the patients required kidney replacement therapy, mostly including renal transplantation [13]. This symptom was previously described as aristolochic acid nephropathy (AAN), a unique type of rapid progress renal fibrosis associated with the prolonged intake of AA-containing Chinese herbs [13][14][15]. DNA-AA adducts were detected in laboratory rodents [4 -12] and in patients suffering from AAN [16 -18].…”

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confidence: 99%

Liquid chromatography—tandem mass spectrometry analysis of the DNA adducts of aristolochic acids

Chan

Zheng

Cai

2007

J. Am. Soc. Mass Spectrom.

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Electrophilic attack of aristolactam-nitrenium ion by the C7 position to the exocyclic amino group in the DNA bases led to the formation of the major adducts. In this study, liquid chromatography coupled with electrospray ionization tandem mass spectrometry was applied to the study of DNA adducts of aristolochic acid (AA). When DNA (bases and CT-DNA) was incubated with AA, dG-AAI, dG-AAII, dA-AAI, dA-AAII, dC-AAI, and dC-AAII were detected and characterized. The dC adducts of AA were identified for the first time. The soft ionization technology allowed detection of the intact DNA adducts. High-resolution MS and MS-MS capabilities of a quadrupole time-of-flight mass spectrometer were shown to be efficient for DNA adducts analysis. DNA-AA adducts showed characteristic fragmentation patterns in MS-MS analysis. The dissociative loss of 116 Da from the DNA-AA adducts, which resulted from internal hydrogen transfer and cleavage at the CON glycosidic bond, provided a characteristic fragment for the structural elucidation. (J Am Soc Mass Spectrom 2007, 18, 642-650)

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Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs

Cited by 978 publications

References 0 publications

Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:Cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid‐DNA adducts found in patients with urothelial cancer

Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:Cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid‐DNA adducts found in patients with urothelial cancer

Enforcement of the ban on aristolochic acids in Chinese traditional herbal preparations on the Dutch market

Liquid chromatography—tandem mass spectrometry analysis of the DNA adducts of aristolochic acids

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