Long-term outcome of acute renal injury induced by Aristolochia manshuriensis Kom in rats. (1/31)

AIM: To investigate the long-term functional and morphological changes of the kidney induced by acute intoxication of Aristolochia manshuriensis Kom in rats. METHODS: Experimental model of acute renal injury was established in the Sprague-Dawley rats with oral administration of decoctions of Chinese herb, Aristolochia manshuriensis Kom, at dosages of 50 g.kg-1.d-1 and 30 g.kg-1.d-1 for 7 consecutive days, and 20 g.kg-1.d-1 for 15 consecutive days. Renal function was assayed at months 0 (right after treatment), 1, 3, and 6 of the experiment. Renal histological examination was also performed. RESULTS: 1) At month 0, the renal functional changes of acute renal injury included azotemia, low molecular weight proteinuria, glycosuria, hypoosmotic urine, and NAG enzymuria. Histopathological changes showed acute tubular necrosis, predominantly at the corticomedullary junction. 2) At months 1 and 3, the renal function of rats of the experiment was gradually restored and histopathologic examination suggested that the tubular lesions gradually recovered. In HE sections, basophilic deposits were observed in the tubular cytoplasm. And interstitial infiltration of inflammatory cells was not prominent. 3) At months 6, renal preneoplastic lesions, renal tumors, and extrarenal tumors occurred in rats. The occurrence of renal preneoplastic lesions at dosages of 50 g.kg-1.d-1, 30 g.kg-1.d-1, and 20 g.kg-1.d-1 were 100.0% at all three doses, renal tumors 42.8%, 25.0%, and 0%, respectively, extrarenal tumors 14.4%, 12.5%, and 12.5%, respectively, and systemic tumors 57.2%, 37.5%, and 12.5%, respectively. The occurrence of basophilic deposits, renal preneoplastic lesions, renal tumors, and extrarenal tumors in normal control group was nil. CONCLUSIONS: 1) Administration of large dosage of Aristolochia manshuriensis Kom induces acute renal failure in rats. 2) The long-term renal function and histopathologic changes of acute renal injury induced by Aristolochia manshuriensis Komrecover spontaneously. 3) Aristolochia manshuriensis Kom has been proved to be oncogenic for the first time.  (+info)

Progression rate of Chinese herb nephropathy: impact of Aristolochia fangchi ingested dose. (2/31)

BACKGROUND: Renal failure after ingestion of Chinese herbs between 1990 and 1992 was related to the replacement of Stephania tetrandra by Aristolochia fangchi (ST-AF), containing nephrotoxic and carcinogenic aristolochic acids. However, the relationship between ST-AF and renal failure is still a matter of debate. We therefore tested the impact of the ST-AF ingested dose on the progression of renal function deterioration. METHODS: Analysis of medical charts and prescriptions between 1990 and 1992 was carried out to determine the presence of risk factors for kidney failure and the cumulative dose of pill components. Individual progression rate of renal impairment was studied by the time-course of the inverse of blood creatinine level (1/P(creat)). RESULTS: Patients were divided into an end-stage renal disease (ESRD) group (n=44) and a chronic renal failure (CRF) group (n=27) according to their P(creat) at the time of this study. The mean number of risk factors (+/-SD) was equally distributed within both groups (1.50+/-0.18 vs 1.59+/-0.17, P=0.74). Patients from the ESRD group ingested significantly higher cumulative doses of ST--AF (192+/-13.1 g vs 138+/- 16.3 g), Magnolia officinalis, (80.1+/-6.3 g vs 59.8+/-11.7 g), diethylpropion (14.7+/-1.4 g vs 10.0+/-1.4 g) and fenfluramine (14.1+/-1.6 g vs 8.7+/-1.3 g). In the ESRD group, some patients who had received steroids had a slower progression to ESRD than the others. In multiple regression analysis, ST-AF emerged as the only significant drug predicting the slope of the progression of renal failure. Moreover, hypothesizing a linear dose-response relationship, the risk of developing ESRD linearly increased with ST-AF doses. CONCLUSIONS: The relationship between the cumulative ST-AF dose and the renal failure progression rate confirms that regular ingestion of Aristolochia sp. extracts is causally involved in the onset of chronic interstitial nephropathy leading to ESRD.  (+info)

Trypanocidal constituents in plants 1. Evaluation of some Mexican plants for their trypanocidal activity and active constituents in Guaco, roots of Aristolochia taliscana. (3/31)

Crude extracts of Mexican medicinal plants were screened for trypanocidal activity against Trypanosoma cruzi, which is the etiological agent for Chagas' disease, one of the most serious protozoan diseases in Latin America. There were 43 kinds of methanolic and other organic extracts from 39 plants which were examined by the preliminary screening test to see immobilization of epimastigotes of T. cruzi in vitro. Eighteen of them showed activity at the concentration of 2 mg/ml after incubation for 2 h, while 13 showed activity at the concentration of 1 mg/ml after incubation for 48 h. Among them, the MeOH extract of roots of Aristolochia taliscana (Aristolochiaceae), locally known as "Guaco," immobilized all the epimastigotes even at lower concentration of 0.5 mg/ml (48 h). In order to identify principal compounds for this activity, the MeOH extract of Guaco was subjected to bioassay-guided fractionation. From the active fractions, four neolignans, eupomatenoid-7 (1), licarin A (2), eupomatenoid-1 (5) and licarin B (6), and two lignans, austrobailignan-7 (3) and fragransin E1 (4) were isolated. Compounds 1-4 immobilized all the epimastigotes at the minimum concentration of 25-75 microg/ml after incubation for 48 h, while compounds 5 and 6 were inactive. Corresponding concentration of gossypol, berberine chloride and harmine was 280 microg/ml, 300 microg/ml and >500 microg/ml, respectively.  (+info)

Neuroprotective effects of 2,5-diaryl-3,4-dimethyltetrahydrofuran neolignans. (4/31)

We previously reported the neurotrophic effects of talaumidin (1) from Aristolochia arcuata MASTERS. In the present study, we compared the neurotrophic and neuroprotective effects of six other 2,5-diaryl-3,4-dimethyltetrahydrofuran neolignans isolated from the same plant, veraguensin (2), galgravin (3), aristolignin (4), nectandrin A (5), isonectandrin B (6), and nectandrin B (7), with compound 1 in primary cultured rat neurons. Compounds 3-7 promoted neuronal survival and neurite outgrowth, among which compounds 6 and 7 showed neurotrophic activity comparable with that of 1. Furthermore, compounds 1-7 protected hippocampal neurons against amyloid beta peptide (Abeta25-35)-induced cytotoxicity, while compounds 1 and 4-7 protected against neuronal death from 1-methyl-4-phenylpyridinium ion (MPP+)-induced toxicity in cultured rat hippocampal neurons.  (+info)

Endemic nephropathy: the case for chronic poisoning by aristolochia. (5/31)

AIM: To explore the hypothesis that chronic dietary poisoning by aristolochic acid could account for the unique geographical distribution, specific pattern of tubulointerstitial fibrosis, occurrence of chronic renal insufficiency, and an increased risk of developing upper urothelial cancer, all of which are associated with endemic nephropathy. METHODS: This case-controlled epidemiologic study consisted of three groups of subjects residing in an endemic region of Croatia: (a) patients meeting WHO criteria for endemic nephropathy (n=28), (b) individuals who have been treated for renal insufficiency secondary to other forms of renal disease (n=30), and (c) apparently healthy residents of the endemic village (n= 30). A detailed questionnaire, designed to collect information on demographics, exposure to potentially toxic substances, diet, agricultural practices, and other factors potentially impacting endemic nephropathy was administered to the three study groups. The seeds of Aristolochia clematitis, obtained from plants growing in the endemic region, were extracted with ethanol and analyzed by high-performance liquid chromatography for their aristolochic acid content. RESULTS: The majority of subjects, including 90% of endemic nephropathy patients, recall that the plant Aristolochia clematitis (birthwort, vucja stopa in Croatian) was frequently found in local meadows and wheat fields between 20 and 30 years ago. At that time, endemic nephropathy patients encountered Aristolochia clematitis significantly more frequently than controls (P=0.035). Since then, all three study groups reported a significant increase in the use of herbicides (P<0.001) and reduction in the prevalence of Aristolochia clematitis (P<0.001). Chemical analysis established that the seeds of A. clematitis contain 0.65% aristolochic acid. It is likely that the harvesting process used by local farmers permitted the seeds of A. clematitis to mingle with the wheat grain. CONCLUSION: Flour used to bake bread, a dietary staple in the endemic region of Croatia, is derived from wheat grain which, in the past, is likely to have been contaminated with seeds of A. clematitis during harvesting. This observation supports the hypothesis that aristolochic acid, a major constituent of the seeds, plays a central role in the development of endemic nephropathy.  (+info)

Role of exposure analysis in solving the mystery of Balkan endemic nephropathy. (6/31)

We evaluated the role of exposure analysis in assessing whether ochratoxin A or aristolochic acid are the agents responsible for causing Balkan endemic nephropathy. We constructed a framework for exposure analysis using the lessons learned from the study of endemic goiter within the context of an accepted general model. We used this framework to develop an exposure analysis model for Balkan endemic nephropathy, evaluated previous findings from the literature on ochratoxin A and aristolochic acid in the context of this model, discussed the strength of evidence for each, and proposed approaches to address critical outstanding questions. The pathway for exposure to ochratoxin A is well defined and there is evidence that humans have ingested ochratoxin A. Factors causing differential exposure to ochratoxin A and how ochratoxin A is implicated in Balkan endemic nephropathy are not defined. Although there is evidence of human exposure to aristolochic acid and that its effects are consistent with Balkan endemic nephropathy, a pathway for exposure to aristolochic acid has been suggested but not demonstrated. Factors causing differential exposure to aristolochic acid are not known. Exposure analysis results suggest that neither ochratoxin A nor aristolochic acid can be firmly linked to Balkan endemic nephropathy. However, this approach suggests future research directions that could provide critical evidence on exposure, which when linked with findings from the health sciences, may be able to demonstrate the cause of this disease and provide a basis for effective public health intervention strategies. One of the key unknowns for both agents is how differential exposure can occur.  (+info)

Role of environmental toxins in endemic (Balkan) nephropathy. October 2006, Zagreb, Croatia. (7/31)

An international symposium, held in Zagreb, Croatia, in October 2006, brought together basic scientists and clinical investigators engaged in research on endemic (Balkan) nephropathy, a chronic renal tubulointerstitial disease of previously unknown cause that often is accompanied by upper urinary tract urothelial cancer. Although this disease is endemic in rural areas of Bosnia, Bulgaria, Croatia, Romania, and Serbia, a similar clinical entity occurs throughout Europe, Asia, and North America. Recent advances in the understanding of endemic nephropathy now favor the causative role of aristolochic acid over the ubiquitous mycotoxin known as ochratoxin A. Specifically, aristolactam-DNA adducts have been found in renal tissues and urothelial cancers of affected patients. A "signature" p53 mutation in the upper urothelial cancer associated with this disease provides evidence of long-term exposure to aristolochic acid. In addition, the renal pathophysiology and histopathology observed in endemic nephropathy most closely resemble the entity known as aristolochic acid nephropathy. Public health authorities in countries harboring this disease are encouraged to reduce the potential for dietary exposure to Aristolochia clematitis.  (+info)

Quantitative and qualitative changes in primary and secondary stem organization of Aristolochia macrophylla during ontogeny: functional growth analysis and experiments. (8/31)

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