RESUMO
Tens of thousands of people in southern Europe suffer from Balkan endemic nephropathy (BEN), and four times as many are at risk. Incidental ingestion of aristolochic acids (AAs), stemming from the ubiquitousAristolochia clematitis(birthwort) weed in the region, leads to DNA adduct-induced toxicity in kidney cells, the primary cause of BEN. Numerous cofactors, including toxic organics and metals, have been investigated, but all have shown small contributions to the overall BEN relative to non-BEN village distribution gradients. Here, we reveal that combustion-derived pollutants from wood and coal burning in Serbia also contaminate arable soil and test as plausible causative factors of BEN. Using a GC-MS screening method, biomass-burning-derived furfural and coal-burning-derived medium-chain alkanes were detected in soil samples from BEN endemic areas levels at up to 63-times and 14-times higher, respectively, than in nonendemic areas. Significantly higher amounts were also detected in colocated wheat grains. Coexposure studies with cultured kidney cells showed that these pollutants enhance DNA adduct formation by AA, - the cause of AA nephrotoxicity and carcinogenicity. With the coincidence of birthwort-derived AAs and the widespread practice of biomass and coal burning for household cooking and heating purposes and agricultural burning in rural low-lying flood-affected areas in the Balkans, these results implicate combustion-derived pollutants in promoting the development of BEN.
Assuntos
Nefropatia dos Bálcãs , Inundações , Nefropatia dos Bálcãs/induzido quimicamente , Nefropatia dos Bálcãs/epidemiologia , Humanos , Carvão Mineral , Sérvia , Poluentes do Solo/toxicidade , Ácidos Aristolóquicos , Animais , Aristolochia/química , Península Balcânica , Madeira , Nefropatias/induzido quimicamenteRESUMO
Aristolochic acids (AAs) are nephrotoxic and carcinogenic nitrophenanthrene carboxylic acids produced naturally by plants from the Aristolochia and Asarum genera, which have been used extensively as herbal medicines. In addition to consuming AA-containing herbal medicinal products, there is emerging evidence that humans are also exposed to AA through the environment. In 2022, the World Health Organization (WHO) called for global action to remove AA exposure sources and to implement preventative measures against the development of AA-associated cancers. Herein, we report the development of a simple and efficient iron powder-packed reduction column that allows online post-column conversion of the nonfluorescing AA to its corresponding strongly fluorescing aristolactam (AL), facilitating the sensitive and selective detection of AA in herbal medicinal products, food grain, arable soil, or groundwater samples by high-performance liquid chromatography with fluorescence detection. Moreover, AL, a group of naturally occurring derivatives of AA that have demonstrated toxicity to cultured bacteria, human cells, and rats, is monitored and quantified simultaneously with AA in one single run without sacrificing sensitivity. In comparison with existing analytical methods for AA measurement, the newly developed method is not only inexpensive and less laborious, but it also offers improved sensitivity. We believe this novel method will find wide application in identifying the presence of AA in food, herbal medicines, and environmental samples, thus assisting in the identification and removal of AA exposure sources.
Assuntos
Ácidos Aristolóquicos , Medicamentos de Ervas Chinesas , Plantas Medicinais , Humanos , Ratos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Aristolóquicos/análise , Plantas Medicinais/química , Medicina Herbária , Medicamentos de Ervas Chinesas/análiseRESUMO
Prolonged exposure to aristolochic acids (AAs) through AA-containing herbal medicine or AA-contaminated food is associated with the development of aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN), both public health risks to which the World Health Organization is calling for global action to remove exposure sources. The AA exposure-induced DNA damage is believed to be related to both the nephrotoxicity and carcinogenicity of AA observed in patients suffering from BEN. While the chemical toxicology of AA is well-studied, we investigated in this study the understated effect of different nutrients, food additives, or health supplements on DNA adduct formation by aristolochic acid I (AA-I). By culturing human embryonic kidney cells in an AAI-containing medium enriched with different nutrients, results showed that cells cultured in fatty acid-, acetic acid-, and amino acid-enriched media produced ALI-dA adducts at significantly higher frequencies than that cultured in the normal medium. ALI-dA adduct formation was most sensitive to amino acids, indicating that amino acid- or protein-rich diets might lead to a higher risk of mutation and even cancer. On the other hand, cells cultured in media supplemented with sodium bicarbonate, GSH, and NAC reduced ALI-dA adduct formation rates, which sheds light on their potential use as risk-mitigating strategies for people at risk of AA exposure. It is anticipated that the results of this study will help to better understand the effect of dietary habits on cancer and BEN development.
Assuntos
Ácidos Aristolóquicos , Nefropatia dos Bálcãs , Nefropatias , Neoplasias , Humanos , Ácidos Aristolóquicos/toxicidade , Adutos de DNA/efeitos adversos , Nefropatia dos Bálcãs/induzido quimicamente , Nefropatias/induzido quimicamente , Dieta/efeitos adversosRESUMO
Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephropathy affecting residents of rural farming areas in many Balkan countries. Although it is generally believed that BEN is an environmental disease caused by multiple geochemical factors with much attention on aristolochic acids (AAs), its etiology remains controversial. In this study, we tested the hypothesis that environmental contamination and subsequent food contamination by polycyclic aromatic hydrocarbons (PAHs) and phthalate esters are AA toxicity factors and important to BEN development. We identified significantly higher concentrations of phenanthrene, anthracene, diethyl phthalate (DEP), dibutyl phthalate (DBP), and benzyl butyl phthalate (BBP) in both maize and wheat grain samples collected from endemic villages than from nonendemic villages. Other PAHs and phthalate esters were also detected at higher concentrations in the soil samples from endemic villages. Subsequent genotoxicity testing of cultured human kidney cells showed an alarming phenomenon that phenanthrene, DEP, BBP, and DBP can interact synergistically with AAs to form elevated levels of AA-DNA adducts, which are associated with both the nephrotoxicity and carcinogenicity of AAs, further increasing their disease risks. This study provides direct evidence that prolonged coexposure to these environmental contaminants via dietary intake may lead to greater toxicity and accelerated development of BEN.
Assuntos
Ácidos Aristolóquicos , Nefropatia dos Bálcãs , Hidrocarbonetos Policíclicos Aromáticos , Ácidos Aristolóquicos/análise , Ácidos Aristolóquicos/toxicidade , Nefropatia dos Bálcãs/induzido quimicamente , Nefropatia dos Bálcãs/epidemiologia , Península Balcânica , Adutos de DNA , Ésteres , Humanos , Ácidos Ftálicos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , SoloRESUMO
Aristolochic acid I (AAI) is a potent nephrotoxic and carcinogenic compound produced by plants of the Aristolochiaceae family and thoroughly investigated as a main culprit in the etiology of Balkan endemic nephropathy (BEN). So far, the AAI exposure was demonstrated to occur through the consumption of Aristolochia clematitis plants as traditional remedies, and through the contamination of the surrounding environment in endemic areas: soil, food and water contamination. Our study investigated for the first time the level of AAI contamination in 141 soil and vegetable samples from two cultivated gardens in non-endemic areas, A. clematitis being present in only one of the gardens. We developed and validated a simple and sensitive ultra-high-performance liquid chromatography-ion trap mass spectrometry method for qualitative and quantitative AAI analysis. The results confirmed the presence of AAI at nanogram levels in soil and vegetable samples collected from the non-endemic garden, where A. clematitis grows. These findings provide additional evidence that the presence of A. clematitis can cause food crops and soil contamination and unveil the pathway through which AAI could move from A. clematitis to other plant species via a common matrix: the soil. Another issue regarding the presence of AAI, in a non-endemic BEN area from Romania, could underlie a more widespread environmental exposure to AAI and explain certain BEN-like cases in areas where BEN has not been initially described.
Assuntos
Aristolochia , Ácidos Aristolóquicos , Nefropatia dos Bálcãs , Ácidos Aristolóquicos/toxicidade , Nefropatia dos Bálcãs/induzido quimicamente , Produtos AgrícolasRESUMO
Balkan endemic nephropathy (BEN) is a slowly progressive interstitial fibrotic disease affecting numerous people living along the Danube River in the Balkan Peninsula, of which aristolochic acids (AAs) produced naturally in Aristolochia plants are key etiological agents. However, the exposure biology of the disease remains poorly understood. Initially, the high incidence of BEN in the Balkan Peninsula was thought to occur through ingestion of bread prepared from flour made with wheat grains comingled with the seeds of Aristolochia clematitis L., an AA-containing weed that grows abundantly in the wheat fields of the affected areas. In this study, by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, we show for the first time that vegetables, in particular root vegetables of endemic areas, are extensively contaminated with AAs taken up through root absorption from the AA-tainted soil. Furthermore, we found a pH dependence of the n-octanol/water partition coefficient (Kow) of AAs, which resulted in a dramatically higher hydrophobicity-driven plant uptake efficiency of AAs into food crops in endemic areas, characterized by higher acidity levels, compared to non-endemic areas. We believe the results of this study have significantly unraveled the mystery surrounding the uneven distribution of BEN incidence.
Assuntos
Ácidos Aristolóquicos/efeitos adversos , Ácidos Aristolóquicos/análise , Nefropatia dos Bálcãs/induzido quimicamente , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/análise , Contaminação de Alimentos/análise , Aristolochia/química , Cromatografia Líquida de Alta Pressão , Abastecimento de Alimentos , Humanos , Concentração de Íons de Hidrogênio , Estrutura Molecular , Sementes/química , Espectrometria de Massas em Tandem , Verduras/químicaRESUMO
RATIONALE: Over the past six decades, residents of farming villages in multiple countries of the Balkan peninsula have been suffering from a unique type of chronic renal disease, Balkan endemic nephropathy (BEN). It was speculated that environmental pollution by aristolochic acids (AAs) produced naturally by Aristolochia clematitis L., a weed that grows in the area, was causing the disease. However, the human exposure pathway to this class of phytotoxin remains obscure. Knowledge of the sink and stability of AAs in the environment would assist in the formulation of policy reducing exposure risk. METHODS: Using our newly developed liquid chromatography/tandem mass spectrometry method of high sensitivity and selectivity, we analysed over 130 soil samples collected from cultivation fields in southern Serbia for the presence of AAs. The environmental stability of AAs was also investigated by incubating soil samples spiked with AAs at various temperatures. RESULTS: The analysis detected AA-I in over two-fifths of the tested samples at sub-µg/kg to µg/kg levels, with higher concentrations observed in more acidic farmland soil. Furthermore, analysis of soil samples incubated at various temperatures revealed half-lives of over 2 months, indicating that AAs are relatively resistant to degradation. CONCLUSIONS: Cultivation soil in southern Serbia is being extensively contaminated with AAs released from the decomposition of A. clematitis weeds. Since AAs are resistant to degradation, it is possible that AAs could have been taken up by root absorption and transported to the edible part of food crops. Prolonged exposure to AA-contaminated food grown from polluted soil could be one of the main aetiological mechanisms of BEN observed in the area.
Assuntos
Aristolochia/química , Ácidos Aristolóquicos/análise , Nefropatia dos Bálcãs/epidemiologia , Solo/química , Nefropatia dos Bálcãs/induzido quimicamente , Cromatografia Líquida , Produtos Agrícolas/química , Humanos , Sérvia/epidemiologia , Espectrometria de Massas em TandemRESUMO
Aristolochic acids (AAs) have been known as potent nephrotoxins since the use of AA-containing herbal medicines was linked with a series of sporadic renal fibrotic nephropathy cases, and yet an estimated 100 million people worldwide are still at risk today because of continued use of similar medicines. However, a similar nephropathic condition is endemic in the rural Balkan regions (e.g., Serbian farming villages) and AAs were again found to be the causative agents. In the case of this Balkan endemic nephropathy, AAs were found to have originated from a widespread local weed Aristolochia clematitis L. In this study, we tested the hypothesis that AAs released from decomposition of A. clematitis were also being leached into groundwater, thus polluting the drinking water of local residents. We initiated the study by developing a dispersive solid-phase extraction-based sample preparation method for water samples suspected of AA contamination. The validated method was then coupled with a liquid chromatography-tandem mass spectrometric method to measure AAs in groundwater samples collected from Serbia. Our study revealed for the first time that groundwater in Serbia is extensively contaminated with AA-I, at ng/L levels. Results also showed that AAs are long-lived water contaminants, with no observable concentration changes over a 2-month period of sample storage.
Assuntos
Ácidos Aristolóquicos , Nefropatia dos Bálcãs , Água Subterrânea , Península Balcânica , Humanos , SérviaRESUMO
Aristolochic acid released from decaying Aristolochia clematitis weed is contaminating soil and food crops in Eastern Europe and is one of the major causes to Balkan endemic nephropathy. Measures should be taken to prevent people from being exposed to these highly potent phytotoxins. Research needs to develop remediation methods.
Assuntos
Aristolochia/química , Ácidos Aristolóquicos/toxicidade , Nefropatia dos Bálcãs/etiologia , Poluentes do Solo/química , Aristolochia/crescimento & desenvolvimento , Aristolochia/metabolismo , Produtos Agrícolas/efeitos dos fármacos , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Humanos , Poluentes do Solo/toxicidade , Poluentes da Água/química , Poluentes da Água/toxicidadeRESUMO
Aristolochic acids (AAs) are carcinogenic and nephrotoxic plant alkaloids present in Aristolochia species, used in traditional medicine. Recent biomolecular and environmental studies have incriminated these toxins as an etiological agent in Balkan endemic nephropathy (BEN), a severe kidney disease occurring in the Balkan Peninsula. The questions on how the susceptible populations are exposed to these toxins have not yet been clearly answered. Exposure to AAs through the food chain, and environmental pollution (soil/dust), could provide an explanation for the presence of BEN in the countries where no folkloric use of the plant has been documented (Bulgaria, Croatia). Additional exposure pathways are likely to occur, and we have shown previously that AAs can contaminate crop plants through absorption from soil, under controlled laboratory environment. Here, we attempt to provide additional support to this potential exposure pathway, by revealing the presence of AAI in soil and soil organic matter samples collected from BEN and non-BEN areas. The samples were processed in order to be analyzed by high-pressure liquid chromatography, and ion trap mass spectrometry. Our results showed the presence of AAI in small concentrations, both in BEN and non-BEN soils, especially where Aristolochia plants and seeds were present.
Assuntos
Ácidos Aristolóquicos/toxicidade , Nefropatia dos Bálcãs/induzido quimicamente , Exposição Ambiental , Substâncias Húmicas , Poluentes do Solo/toxicidade , Ácidos Aristolóquicos/análise , Cromatografia Líquida de Alta Pressão , Produtos Agrícolas , Humanos , Espectrometria de Massas , Estações do Ano , Poluentes do Solo/análise , Espectrofotometria UltravioletaRESUMO
Balkan endemic nephropathy (BEN) is a chronic kidney disease that predominantly affects inhabitants of rural farming communities along the Danube River tributaries in the Balkans. Long-standing research has identified dietary exposure to aristolochic acids (AAs) as the principal toxicological cause. This study investigates the pathophysiological role of anemia in BEN, noting its earlier and more severe manifestation in BEN patients compared to those with other chronic kidney diseases. Utilizing a mouse model, our research demonstrates that prolonged exposure to aristolochic acid I (AA-I) (the most prevalent AA variant) leads to significant red blood cell depletion through DNA damage, such as DNA adduct formation in bone marrow, prior to observable kidney function decline. Furthermore, in vitro experiments with kidney cells exposed to lowered oxygen and pH conditions mimicking an anemia environment show enhanced DNA adduct formation, suggesting increased AA-I mutagenicity and carcinogenicity. These findings indicate for the first time a positive feedback mechanism of AA-induced anemia, DNA damage, and kidney impairment in BEN progression. These results not only advance our understanding of the underlying mechanisms of BEN but also highlight anemia as a potential target for early BEN diagnosis and therapy.
Assuntos
Anemia , Ácidos Aristolóquicos , Nefropatia dos Bálcãs , Adutos de DNA , Ácidos Aristolóquicos/toxicidade , Ácidos Aristolóquicos/efeitos adversos , Nefropatia dos Bálcãs/induzido quimicamente , Nefropatia dos Bálcãs/metabolismo , Nefropatia dos Bálcãs/genética , Adutos de DNA/metabolismo , Animais , Camundongos , Humanos , Anemia/induzido quimicamente , Anemia/metabolismo , Anemia/genética , Masculino , Dano ao DNA/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Rim/efeitos dos fármacos , Rim/metabolismo , FemininoRESUMO
Aristolochic acids (AAs) are nephrotoxic and carcinogenic derivatives found in several Aristolochia species. To date, the toxicity of AAs has been inferred only from the effects observed in patients suffering from a kidney disease called "aristolochic acid nephropathy" (AAN, formerly known as "Chinese herbs nephropathy"). More recently, the chronic poisoning with Aristolochia seeds has been considered to be the main cause of Balkan endemic nephropathy, another form of chronic renal failure resembling AAN. So far, it was assumed that AAs can enter the human food chain only through ethnobotanical use (intentional or accidental) of herbs containing self-produced AAs. We hypothesized that the roots of some crops growing in fields where Aristolochia species grew over several seasons may take up certain amounts of AAs from the soil, and thus become a secondary source of food poisoning. To verify this possibility, maize plant (Zea mays) and cucumber (Cucumis sativus) were used as a model to substantiate the possible significance of naturally occurring AAs' root uptake in food chain contamination. This study showed that the roots of maize plant and cucumber are capable of absorbing AAs from nutrient solution, consequently producing strong peaks on ultraviolet HPLC chromatograms of plant extracts. This uptake resulted in even higher concentrations of AAs in the roots compared to the nutrient solutions. To further validate the measurement of AA content in the root material, we also measured their concentrations in nutrient solutions before and after the plant treatment. Decreased concentrations of both AAI and AAII were found in nutrient solutions after plant growth. During this short-term experiment, there were much lower concentrations of AAs in the leaves than in the roots. The question is whether these plants are capable of transferring significant amounts of AAs from the roots into edible parts of the plant during prolonged experiments.
Assuntos
Ácidos Aristolóquicos/metabolismo , Nefropatia dos Bálcãs/etiologia , Cucumis sativus/metabolismo , Doenças Transmitidas por Alimentos/complicações , Zea mays/metabolismo , Ácidos Aristolóquicos/toxicidade , Cromatografia Líquida de Alta Pressão , Cucumis sativus/intoxicação , Humanos , Raízes de Plantas/metabolismo , Zea mays/intoxicaçãoRESUMO
Described in the 1950s, Balkan Endemic Nephropathy (BEN) has been recognized as a chronic kidney disease (CKD) with clinical peculiarities and multiple etiological factors. Environmental contaminants - aromatic compounds, mycotoxins and phytotoxins like aristolochic acids (AAs) - polluting food and drinking water sources, were incriminated in BEN, due to their nephrotoxic and carcinogenic properties. The implication of AAs in BEN etiology is currently a highly debated topic due to the fact that they are found within the Aristolochiaceae plants family, used around the globe as traditional medicine and they were also incriminated in Aristolochic Acid Nephropathy (AAN). Exposure pathways have been investigated, but it is unclear to what extent AAs are acting alone or in synergy with other cofactors (environmental, genetics) in triggering kidney damage. Experimental studies strengthen the hypothesis that AAI, the most studied compound in the AAs class, is a significant environmental contaminant and a most important causative factor of BEN. The aim of this review is to compile information about the natural exposure pathways to AAI, via traditional medicinal plants, soil, crop plants, water, food, air. Data that either supports or contradicts the AAI theory concerning BEN etiology was consolidated and available solutions to reduce human exposure were discussed. Because AAI is a phytotoxin with physicochemical properties that allow its transportation in environmental matrices from different types of areas (endemic, nonendemic), and induce CKDs (BEN, AAN) and urinary cancers through bioaccumulation, this review aims to shed a new light on this compound as a biogenic emerging pollutant.
Assuntos
Ácidos Aristolóquicos , Nefropatia dos Bálcãs , Insuficiência Renal Crônica , Ácidos Aristolóquicos/toxicidade , Nefropatia dos Bálcãs/induzido quimicamente , Nefropatia dos Bálcãs/epidemiologia , Saúde Ambiental , Feminino , Humanos , Masculino , Insuficiência Renal Crônica/induzido quimicamenteRESUMO
Aristolochic acids (AAs) are persistent soil pollutants in the agricultural fields of the Balkan Peninsula that are endemic for Aristolochia clematitis L. This class of carcinogenic and nephrotoxic phytotoxins is taken up by crops through root absorption and contaminates staple foods across the peninsula. Human exposure to AAs via dietary intake has recently been recognized as a cause of Balkan endemic nephropathy. For the sake of public health, human exposure to AAs from all sources should be minimized in a timely manner. However, currently, there is no available remediation method to remove AAs from soil. In this study, we developed the first soil remediation method for AAs using Fenton's reagent (FR), a combination of ferrous ion and hydrogen peroxide, and optimized factors, including pH, temperature, time, and dose of FR, to achieve the best degradation performance. The maximum AA degradation efficiency was found to be >97% in soil with 500 µg kg-1 of AAs. We anticipate that this developed method, mediated via Fenton reaction, will be useful to effectively eliminate AAs from the Balkan farmlands.
Assuntos
Solo , Aristolochia , Ácidos Aristolóquicos , Nefropatia dos Bálcãs , Península Balcânica , Humanos , Peróxido de HidrogênioRESUMO
Prolonged dietary exposure to AA-contaminated food crops cultivated in contaminated farmland was shown to be one of the main culprits of Balkan endemic nephropathy. Ultra-sensitive methods for the detection of AA at trace levels are important for surveillance purposes. We report the development of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for AA-detection. One striking feature of the method is that the Zn/H+-induced nitroreduction convert AA into their respective aristolactams, which dramatically enhances their analytical sensitivity. The method was applied to quantitate AA in food grains and soil samples collected from farming villages of Serbia, and flour samples purchased from supermarkets. To the best of our knowledge, this is the first report of detecting AA in food ingredients available in supermarkets, which is alarming because it reveals AA poses insidious threats not only to residents of rural farming villages, but also to people residing in urban areas.
Assuntos
Ácidos Aristolóquicos/análise , Cromatografia Líquida , Exposição Dietética , Contaminação de Alimentos/análise , Poluentes do Solo/análise , Espectrometria de Massas em Tandem , Produtos Agrícolas/química , Farinha/análise , Análise de Alimentos , Limite de Detecção , Sensibilidade e Especificidade , Sérvia , Solo/químicaRESUMO
Aristolochic acids (AAs) are nitrophenanthrene carboxylic acids naturally produced by Aristolochia plants. These plants were widely used to prepare herbal remedies until AAs were observed to be highly nephrotoxic and carcinogenic to humans. Although the use of AA-containing Aristolochia plants in herbal medicine is prohibited in countries worldwide, emerging evidence nevertheless has indicated that AAs are the causative agents of Balkan endemic nephropathy (BEN), an environmentally derived disease threatening numerous residents of rural farming villages along the Danube River in countries of the Balkan Peninsula. This perspective updates recent findings on the identification of AAs in food as a result of the root uptake of free AAs released from the decayed seeds of Aristolochia clematitis L., in combination with their presence and fate in the environment. The potential link between AAs and the high prevalence of chronic kidney diseases in China is also discussed.
RESUMO
Balkan endemic nephropathy is a chronic tubulointerstitial disease with insidious onset, slowly progressing to end-stage renal disease and frequently associated with urothelial carcinoma of the upper urinary tract (UTUC). It was described in South-East Europe at the Balkan peninsula in rural areas around tributaries of the Danube River. After decades of intensive investigation, the causative factor was identified as the environmental phytotoxin aristolochic acid (AA) contained in Aristolochia clematitis, a common plant growing in wheat fields that was ingested through home-baked bread. AA initially was involved in the outbreak of cases of rapidly progressive renal fibrosis reported in Belgium after intake of root extracts of Aristolochia fangchi imported from China. A high prevalence of UTUC was found in these patients. The common molecular link between Balkan and Belgian nephropathy cases was the detection of aristolactam-DNA adducts in renal tissue and UTUC. These adducts are not only biomarkers of prior exposure to AA, but they also trigger urothelial malignancy by inducing specific mutations (A:T to T:A transversion) in critical genes of carcinogenesis, including the tumor-suppressor TP53. Such mutational signatures are found in other cases worldwide, particularly in Taiwan, highlighting the general public health issue of AA exposure by traditional phytotherapies.
Assuntos
Ácidos Aristolóquicos/toxicidade , Nefropatia dos Bálcãs/induzido quimicamente , Carcinoma de Células de Transição/induzido quimicamente , Exposição Ambiental/efeitos adversos , Neoplasias Renais/induzido quimicamente , Neoplasias Ureterais/induzido quimicamente , Animais , Aristolochia , Nefropatia dos Bálcãs/diagnóstico , Nefropatia dos Bálcãs/patologia , Nefropatia dos Bálcãs/terapia , Carcinógenos/toxicidade , Adutos de DNA , Humanos , Programas de RastreamentoRESUMO
Balkan endemic nephropathy (BEN) occurs in Serbia, Bulgaria, Romania, Bosnia and Herzegovina, and Croatia. BEN has been characterized as a chronic, slowly progressive renal disease of unknown etiology. In this study, we examined the influence of soluble organic compounds in drinking water leached from Pliocene lignite from BEN-endemic areas on plasma lecithin-cholesterol acyltransferase (LCAT) activity. We found that changes for all samples were the most prominent for the dilution category containing 90% plasma and 10% of diluting media. Water samples from BEN villages from Serbia and Romania showed higher LCAT inhibiting activity (p=0.02) and (p=0.003), respectively, compared to deionised water and non-endemic water. A secondary LCAT deficiency could result from this inhibitory effect of the organic compounds found in endemic water supplies and provide an ethiopathogenic basis for the development of BEN in the susceptible population.
Assuntos
Nefropatia dos Bálcãs/etiologia , Carvão Mineral/análise , Compostos Orgânicos/toxicidade , Fosfatidilcolina-Esterol O-Aciltransferase/metabolismo , Nefropatia dos Bálcãs/enzimologia , HumanosRESUMO
Exposure to aristolochic acids (AAs) from Aristolochia plants is one of the major global causes of nephropathy, including Balkan endemic nephropathy (BEN); renal failure; and urothelial cancer. The high incidence of BEN on the Balkan Peninsula is assumed to result from consumption of Aristolochia clematitis L. seeds coharvested with crops. Here, we show that AAs are long-lived soil contaminants that enter wheat and maize plants by root uptake with strong pH dependence. Soil and crops from Serbian farms in areas endemic for A. clematitis were found to be extensively contaminated with AAs, with contamination strongly correlated with local incidence of BEN. The persistence of AAs as soil contaminants suggests that weed control for A. clematitis plants is needed to reduce the incidence of BEN and aristolochic acid nephropathy, systematic surveys of soil and crop AA levels would identify high-risk regions, and it is imperative to research soil-remediation methods.
Assuntos
Ácidos Aristolóquicos/efeitos adversos , Exposição Dietética/efeitos adversos , Nefropatias/induzido quimicamente , Poluentes do Solo/efeitos adversos , Humanos , Nefropatias/epidemiologia , Estrutura Molecular , Raízes de Plantas/química , Sérvia/epidemiologia , Triticum/química , Zea mays/químicaRESUMO
While to date investigations provided convincing evidence on the role of aristolochic acids (AAs) in the etiology of Balkan endemic nephropathy (BEN) and upper urothelial cancer (UUC), the exposure pathways by which AAs enter human bodies to cause BEN and UUC remain obscure. The goal of this study is to test the hypothesis that environmental pollution by AAs and root uptake of AAs in the polluted soil may be one of the pathways by which AAs enter the human food chain. The hypothesis driving this study was that the decay of Aristolochia clematitis L., a AA-containing herbaceous plant that is found growing widespread in the endemic regions, could release free AAs to the soil, which could be taken up by food crops growing nearby, thereby transferring this potent human nephrotoxin and carcinogen into their edible parts. Using the highly sensitive and selective high-performance liquid chromatography coupled with fluorescence detection method, we identified and quantitated in this study for the first time AAs in corn, wheat grain, and soil samples collected from the endemic village Kutles in Serbia. Our results provide the first direct evidence that food crops and soil in the Balkans are contaminated with AAs. It is possible that the presence of AAs in edible parts of crops originating from the AA-contaminated soil could be one of the major pathways by which humans become exposed to AAs.