Valvular heart disease and Chinese-herb nephropathy

Vanherweghem, Jean‐Louis; Cuykens, J. J.; Vandenbergh, Ph; Bouman, KP; Hagers, Yves

doi:10.1016/s0140-6736(05)60661-7

Cited by 9 publications

(2 citation statements)

References 9 publications

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“…Although no other significant risk factor was identified, since most of the patients were treated with appetite suppressants as well as acetazolamide, it cannot be excluded that the former drugs, with vasoconstrictive properties (De Broe, 1999), or the latter agents, which alkalize the urine (Violon, 1997), enhance the toxicity of AA. Indeed, aortic insufficiency was reported in a few Belgian AAN patients (Reginster et al, 1997) and it was suggested that this valvular heart disease was more likely caused by the concomitant intake of appetite suppressants such as fenfluramine (Vanherweghem, 1997;van Ypersele de Strihou, 1998).…”

Section: Aa Nephropathy and Urothelial Cancermentioning

confidence: 99%

Aristolochic acid as a probable human cancer hazard in herbal remedies: a review

Arlt

Stiborová²,

Schmeiser³

2002

Mutagenesis

439

411

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The old herbal drug aristolochic acid (AA), derived from Aristolochia spp., has been associated with the development of a novel nephropathy, designated aristolochic acid nephropathy (AAN), and urothelial cancer in AAN patients. There is clear evidence that the major components of the plant extract AA, aristolochic acid I (AAI) and aristolochic acid II (AAII), both nitrophenanthrene carboxylic acids, are genotoxic mutagens forming DNA adducts after metabolic activation through simple reduction of the nitro group. Several mammalian enzymes have been shown to be capable of activating both AAI and AAII in vitro and in cells. The activating metabolism has been elucidated and is consistent with the formation of a cyclic nitrenium ion with delocalized charge leading to the preferential formation of purine adducts bound to the exocyclic amino groups of deoxyadenosine and deoxyguanosine. The predominant DNA adduct in vivo, 7-(deoxyadenosin-N(6)-yl)aristolactam I (dA-AAI), which is the most persistent of the adducts in target tissue, is a mutagenic lesion leading to AT-->TA transversions in vitro. This transversion mutation is found at high frequency in codon 61 of the H-ras oncogene in tumours of rodents induced by AAI, suggesting that dA-AAI might be the critical lesion in the carcinogenic process in rodents. DNA-binding studies confirmed that both AAs bind to the adenines of codon 61 in the H-ras mouse gene and preferentially to purines in the human p53 gene. In contrast, the molecular mechanism of renal interstitial fibrosis in humans after chronic administration of AA remains to be explored. However, preliminary findings suggest that DNA damage by AA is not only responsible for the tumour development but also for the destructive fibrotic process in the kidney. It is concluded that there is significant evidence that AA is a powerful nephrotoxic and carcinogenic substance with an extremely short latency period, not only in animals but also in humans. In particular, the highly similar metabolic pathway of activation and resultant DNA adducts of AA allows the extrapolation of carcinogenesis data from laboratory animals to the human situation. Therefore, all products containing botanicals known to or suspected of containing AA should be banned from the market world wide.

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Section: Aa Nephropathy and Urothelial Cancermentioning

confidence: 99%

Aristolochic acid as a probable human cancer hazard in herbal remedies: a review

Arlt

Stiborová²,

Schmeiser³

2002

Mutagenesis

439

411

View full text Add to dashboard Cite

show abstract

“…Auch die unter dem Schlankheitsregime aufgetretenen Fälle von Aorteninsuffizienz wurden teilweise den chinesischen Kräutern angelastet, doch dieser Vorwurf war nicht haltbar [55,65].…”

Section: Besonderheit Der Belgischen Nephropathiefälleunclassified

Über die Aristolochia-Nephropathie - Phytotherapie -

Wiebrecht¹

2000

Dt Ztschr f Akup

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Chinese herbs nephropathy-associated slimming regimen induces tumours in the forestomach but no interstitial nephropathy in rats

Cosyns

Goebbels

Liberton

et al. 1998

Archives of Toxicology

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Chinese herbs nephropathy (CHN), a rapidly progressive interstitial fibrosis of the kidney, has been described in approximately 100 young Belgian women who had followed a slimming regimen containing some Chinese herbs. In 4 patients multifocal transitional cell carcinomas (TCC) were observed. Aristolochic acid (AA), suspected as the causal factor of CHN, is a well known carcinogen but its ability to induce fibrosis has never been demonstrated. The objective of this study was to evaluate the latter using doses of AA, durations of intoxication and delays of sacrifice known to yield tumours in rats. We also tested the hypothesis that a possible fibrogenic role of AA was enhanced by the other components of the slimming regimen. Male and female rats were treated orally with 10 mg isolated AA/kg per day for 5 days/week, or with approximately 0.15 mg AA/ kg per day 5 days/week contained in the herbal powder together with the other components prescribed in the slimming pills for 3 months. The animals were killed respectively 3 and 11 months later. At sacrifice, animals in both groups had developed the expected tumours but not fibrosis of the renal interstitium. Whether the fibrotic response observed in man is due to species and/or strain related differences in the response to AA or to other factors, remains to be determined. Interestingly, despite the addition of fenfluramine and diethylpropion, two drugs incriminated in the development of valvular heart disease, no cardiac abnormalities were observed.

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Valvular heart disease and Chinese-herb nephropathy

Cited by 9 publications

References 9 publications

Aristolochic acid as a probable human cancer hazard in herbal remedies: a review

Aristolochic acid as a probable human cancer hazard in herbal remedies: a review

Über die Aristolochia-Nephropathie - Phytotherapie -

Chinese herbs nephropathy-associated slimming regimen induces tumours in the forestomach but no interstitial nephropathy in rats

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