Nephrotoxicity of Natural Products: Aristolochic Acid and Fungal Toxins

Bunel, Valérian; Souard, Florence; Antoine, Marie-Hélène; Stévigny, Caroline; Nortier, Joëlle

doi:10.1016/b978-0-12-801238-3.64093-x

Cited by 11 publications

(15 citation statements)

References 367 publications

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“…Finally, there is no evidence of general OTA toxicity in human beings. 16 The AA hypothesis was first launched in 1969 by Ivi c, 5 who observed that the plant A clematitis grew much more abundantly in Serbian-endemic than in nonendemic areas. Ivi c 5 realized that farmers unaware of the plant's toxicity brought grain contaminated by Aristolochia seeds for grinding into flour and concluded that the bread of those peasants was poisonous.…”

Section: Epidemiology and Etiology Of Benmentioning

confidence: 99%

“…The plant extract AA is a mixture of structurally related nitrophenanthrene carboxylic acids, with aristolochic acid I (8-methoxy-6-nitro-phenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic acid; AAI) and aristolochic acid II (6-nitro-phenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic acid; AAII) being the major components. 16 Both compounds are mutagenic and genotoxic, 52 but AAI is considered to be responsible for AA-mediated nephropathy. Although AAI might directly cause interstitial nephropathy, enzymatic activation of AAI is required to exert its genotoxic (ie, DNA damaging) properties.…”

Section: Dna Adducts Formed By Aa As Markers Of Exposure and Early Phase Of Utucmentioning

confidence: 99%

“…13 In fact, their first use to stimulate the expulsion of the placenta during childbirth was responsible for coining the name "Aristos lokos" or "excellent delivery." 16 Because the plants also were recommended for treating snake bites, Aristolochia were included in the preparation of theriac. As a result, they were prescribed for treating gout (Dutchman's pipe).…”

mentioning

confidence: 99%

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Balkan Endemic Nephropathy and the Causative Role of Aristolochic Acid

Jelaković

Dika

Arlt

et al. 2019

Seminars in Nephrology

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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 homebaked 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.

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Section: Epidemiology and Etiology Of Benmentioning

confidence: 99%

Section: Dna Adducts Formed By Aa As Markers Of Exposure and Early Phase Of Utucmentioning

confidence: 99%

mentioning

confidence: 99%

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Balkan Endemic Nephropathy and the Causative Role of Aristolochic Acid

Jelaković

Dika

Arlt

et al. 2019

Seminars in Nephrology

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“…Aristolochic acids (AAs) are active compounds contained in medicinal plants from the Aristolochia and Asarum species. The consumption of AAs is now recognized as a cause of iatrogenic and environmental chronic kidney disease (CKD), namely, aristolochic acid nephropathy (AAN) [1,2]. The onset and progression of renal fibrosis are experimentally characterized by an acute phase (i.e., tubular necrosis of the S3 segment of the proximal tubule reflecting acute kidney injury (AKI)) followed by marked tubular atrophy and interstitial fibrosis leading to end-stage kidney disease [3].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells

Antoine

Husson

Yankep

et al. 2022

Toxins

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Aristolochic acids (AAs) are powerful nephrotoxins that cause severe tubulointerstitial fibrosis. The biopsy-proven peritubular capillary rarefaction may worsen the progression of renal lesions via tissue hypoxia. As we previously observed the overproduction of reactive oxygen species (ROS) by cultured endothelial cells exposed to AA, we here investigated in vitro AA-induced metabolic changes by 1H-NMR spectroscopy on intracellular medium and cell extracts. We also tested the effects of nebivolol (NEB), a β-blocker agent exhibiting antioxidant properties. After 24 h of AA exposure, significantly reduced cell viability and intracellular ROS overproduction were observed in EAhy926 cells; both effects were counteracted by NEB pretreatment. After 48 h of exposure to AA, the most prominent metabolite changes were significant decreases in arginine, glutamate, glutamine and glutathione levels, along with a significant increase in the aspartate, glycerophosphocholine and UDP-N-acetylglucosamine contents. NEB pretreatment slightly inhibited the changes in glutathione and glycerophosphocholine. In the supernatants from exposed cells, a decrease in lactate and glutamate levels, together with an increase in glucose concentration, was found. The AA-induced reduction in glutamate was significantly inhibited by NEB. These findings confirm the involvement of oxidative stress in AA toxicity for endothelial cells and the potential benefit of NEB in preventing endothelial injury.

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“…Despite warnings from the Food and Drug Administration (FDA), the European Medicines Agency (EMA) and IARC regarding the safety of products containing AA, AAN cases remain frequently described worldwide [5,15,16]. Moreover, given the fact that the nephrotoxic effect of AA is irreversible and that chronic kidney failure as well as carcinogenic effects may develop very slowly after the initial exposure, AAN and associated cancers are likely to become a major public health issue in the next few years [15,16,17].…”

Section: Introductionmentioning

confidence: 99%

A Translational Metabonomic Assessment of Aristolochic Acid- Induced Nephropathies

Jadot¹,

Duquesne²,

Declèves³

et al. 2018

Advances in Nephropathy

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Aristolochic acid nephropathy (AAN) is a global term including any form of toxic interstitial nephropathy that is caused either by the ingestion of plants containing aristolochic acids (AA) as part of traditional phytotherapies or by the environmental contaminants in food. Originally, AAN was reported in Belgium in individuals having ingested slimming pills containing powdered root extracts of a Chinese herb, Aristolochia fangchi. However, it is estimated that exposure to AA affects thousands of people all over the world, particularly in the Balkans, Taiwan and China. Despite warnings from the Regulatory Agencies regarding the safety of products containing AA, many AAN cases remain frequently described worldwide. This chapter aims at giving a global picture of AAN through the descriptions of clinical cases and animal models, which were developed to better understand the mode of action of AA when inducing acute/chronic kidney diseases. Major advances in the translational research on biomarkers of AAN are reviewed, with an intended emphasis on the "omics" assessment of this nephrotoxicity.

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Nephrotoxicity of Natural Products: Aristolochic Acid and Fungal Toxins

Cited by 11 publications

References 367 publications

Balkan Endemic Nephropathy and the Causative Role of Aristolochic Acid

Balkan Endemic Nephropathy and the Causative Role of Aristolochic Acid

Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells

A Translational Metabonomic Assessment of Aristolochic Acid- Induced Nephropathies

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