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Kidney Int ; 59(6): 2164-73, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11380818


BACKGROUND: Chinese herbs nephropathy (CHN) is a new type of subacute interstitial nephritis that is attributed to aristolochic acid (AA), which inadvertently has been included in slimming pills. The contribution of other simultaneously prescribed drugs remains disputed. In the present study, the effects of a chronic intake of AA given as a single drug was evaluated through renal histology and function in rabbits. METHODS: Female New Zealand White rabbits were injected intraperitoneally with either 0.1 mg AA/kg or with saline 5 days a week for 17 to 21 months. Body weight, renal function, and urinary excretion of glucose and low molecular weight proteins were monitored prior to sacrifice at the end of the study period. RESULTS: All animals given AA developed renal hypocellular interstitial fibrosis, which was classified into three patterns. Fibrosis was confined to medullary rays (MRs) in pattern I (N = 3), extended to the outer cortical labyrinth (OCL) in pattern II (N = 2), and eventually to the inner cortical labyrinth (ICL) in pattern III (N = 6). Fibrosis in MR and OCL was associated with mainly proximal tubular epithelial cell flattening. All treated animals displayed urothelial atypia. Three of them also developed tumors of the urinary tract. No significant pathologic changes were found in control rabbits. AA-treated animals differed from controls by an impaired growth, increased serum creatinine, glucosuria, tubular proteinuria, and anemia. CONCLUSION: The observed pattern of renal histopathological lesions and disorders of the renal function, as well as urothelial atypia and malignancy, are very reminiscent of CHN. Our observations therefore support a causal role of AA alone in the genesis of this new nephropathy.

Ácidos Aristolóquicos , Medicamentos Herbarios Chinos/toxicidad , Inhibidores Enzimáticos/toxicidad , Nefritis Intersticial/inducido químicamente , Fenantrenos/toxicidad , Animales , Modelos Animales de Enfermedad , Femenino , Fibrosis , Riñón/patología , Nefritis Intersticial/patología , Tamaño de los Órganos , Conejos , Estómago/patología
Arch Toxicol ; 72(11): 738-43, 1998 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9879812


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.

Fármacos Antiobesidad/toxicidad , Ácidos Aristolóquicos , Fibrina/efectos de los fármacos , Nefritis Intersticial/inducido químicamente , Fenantrenos/toxicidad , Neoplasias Gástricas/inducido químicamente , Animales , Carcinógenos/toxicidad , Medicamentos Herbarios Chinos/química , Femenino , Fibrina/metabolismo , Masculino , Ratas , Ratas Wistar