Aristolochic acid I as an emerging biogenic contaminant involved in chronic kidney diseases: A comprehensive review on exposure pathways, environmental health issues and future challenges

Lukinich-Gruia, Alexandra Teodora; Nortier, Joëlle; Pavlović, Nikola M.; Мilоvаnоvić, Drаgаn; Popović, Miloš; Drăghia, Lavinia Paula; Păunescu, Virgil; Tatu, Calin A.

doi:10.1016/j.chemosphere.2022.134111

Cited by 23 publications

(17 citation statements)

References 87 publications

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“…CKD can be caused by various factors, including the inappropriate use of drugs ( Romagnani et al, 2017 ) and prolonged exposure to a toxicant–contaminated environment (i.e., Balkan endemic nephropathy due to AAI) ( Lukinich-Gruia et al, 2022 ). Aristolochic acids (AAs), which are produced by Aristolochia and Asarum , have been widely used as herbal TCMs ( Anger et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological mechanisms of Fuzheng Huayu formula for Aristolochic acid I–induced kidney fibrosis through network pharmacology

Wang

et al. 2022

Front. Pharmacol.

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Renal fibrosis, characterized by the destruction of renal tubules and interstitial capillaries and the accumulation of extracellular matrix proteins, is a common outcome of chronic renal diseases and has a wide spectrum of etiologies. Fibrosis can affect any organ and has similar pathological mechanisms. Fuzheng Huayu formula (FZHY), as the approved anti-liver fibrosis medicine in China, also can inhibit the kidney fibrosis induced by HgCl2 or unilateral ureteral obstruction. However, little is known about the mechanisms underlying the beneficial effects of FZHY on renal fibrosis. This study aimed to identify the mechanisms of FZHY acts on renal fibrosis through network pharmacological analysis and in vivo experiments. Data from online databases were mined and screened to predict the target related genes of FZHY acts on renal fibrosis. The STRING and Cytoscape were used to construct the protein-protein interaction (PPI) networks for FZHY and CKD target proteins. Mouse models with CKD induced by Aristolochic Acid I (AAI) were used to validate the effects of FZHY on renal fibrosis and their underlying mechanisms by detecting kidney function, renal fibrosis, and related intersection genes. A total of 129 FZHY–CKD crossover proteins were filtered and constructed into a protein–protein interaction network complex and designated as the potential targets of FZHY. One of the highest-scoring genes, FOS, and its related signaling pathways were more activated in CKD. The results demonstrated that FZHY can exert an anti-renal fibrosis effect by improving the levels of serum creatinine and blood urea nitrogen and alleviating excessive collagen deposition in kidney tissue, FZHY also could reduce the levels of TNF-α, IL-1β, and IL-6 and inhibit the expression of MAPK/FOS signal molecules. Our study findings provide insights into predicting the effects of FZHY on CKD through network pharmacology. FZHY can protect the kidney from inflammatory injury caused by AAI and can antagonize inflammatory factor-stimulated MAPK/FOS activation in fibrotic kidneys. These effects constitute the mechanisms of FZHY for renal fibrosis.

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Section: Discussionmentioning

confidence: 99%

Pharmacological mechanisms of Fuzheng Huayu formula for Aristolochic acid I–induced kidney fibrosis through network pharmacology

Wang

et al. 2022

Front. Pharmacol.

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“…Aristolochic acids are reported to exert their toxicological effects as phytotoxins through the common use of Aristolochia as an ingredient in formulations to reduce body weight, nowadays called aristolochic acid nephropathy (Gifford et al, 2017). Relevant literature confirms the toxicological profile of aristolochic acids, which are recognized as highly carcinogenic and toxic metabolites with potential health implications both directly, in their interactions in culinary and medicinal uses, as well as indirectly, in the form of environmental pollutants (Lukinich-Gruia et al, 2022). Many countries do not allow the use of Aristolochia as herbal medicines or food supplements due to the toxicity of aristolochic acid constituents.…”

Section: Introduction 1the Genus Aristolochia: Between Poison and Med...mentioning

confidence: 99%

Ethnomedical uses of Yawar Panga (Aristolochia didyma) in a therapeutic community dedicated to the treatment of drug addiction in the Peruvian Amazon

Politi¹,

Simonet²,

Kube³

et al. 2023

NRFHH

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Aristolochia didyma (Yawar Panga) and other Aristolochia species are used as traditional herbal remedies with potent emetic properties. Scientific data for such Yawar Panga species, however, are scarce in the literature. The aim of this study was to describe the use of Yawar Panga within the context of the therapeutic community Takiwasi, in which the plant is used as part of the protocol for the rehabilitation of individuals with drug addiction. Fieldwork with experts in the administration of Yawar Panga at Takiwasi Center, as well as a retrospective qualitative analysis of experiences with this plant remedy in a residential inpatient population were performed. In-silico analysis of the main constituents of A. didyma as represented in the literature was completed in order to identify its putative pharmacological targets. The therapists interviewed consider Yawar Panga to be the most potent purga at Takiwasi and consider it especially useful in attenuating addiction withdrawal syndrome. From the patient’s perspective, this plant induces strong physical effects, and commonly precipitates effects in the oneiric and emotional dimensions. GABA B seems to be the receptor involved in the emesis induced by the phytochemicals contained in this plant species. Despite some relevant concerns related to the safety of the genus Aristolochia in modern western pharmacopoeias, some species, including A. didyma, are routinely used in the context of traditional herbal medicine in the Peruvian Amazon. Further phyto-pharmacological investigations would be helpful to elaborate this species’ medical utility, especially within the context of addiction treatment.

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“…It is not known whether aristolochic acid, a compound with strong carcinogenicity and nephrotoxicity to humans, will become a new environmental pollutant. Balkan endemic nephropathy (BEN) is a known chronic interstitial nephritis disease in the Balkans of southeastern Europe [ 11 , 21 ]. A. clematitis L is widely distributed in cultivated soils in Serbia, and AAs may be the cause of BEN [ 20 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Uptake, Translocation, and Fate of Carcinogenic Aristolochic Acid in Typical Vegetables in Soil−Plant Systems

Zhang

Wang

et al. 2022

Molecules

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When Aristolochia plants wilt and decay, aristolochic acids (AAs) are released into the soil, causing soil contamination. It has been demonstrated that aristolochic acid can be accumulated and enriched in crops through plant uptake. However, there is a lack of systematic studies on the migration and accumulation of AAs in a realistic simulated soil environment. In this study, Aristolochia herbal extracts were mixed with soil for growing three typical vegetables: lettuce, celery, and tomato. The contents of AAs in the above-mentioned plants were determined by an established highly sensitive LC-MS/MS method to study the migration and accumulation of AAs. We found that AAs in the soil can be transferred and accumulated in plants. AAs first entered the roots, which were more likely to accumulate AAs, and partially entered the above-ground parts. This further confirms that AAs can enter the food chain through plants and can have serious effects on human health. It was also shown that plants with vigorous growth and a large size absorbed AAs from the soil at a faster rate. The more AAs present in the soil, the more they accumulated in the plant.

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Aristolochic acid I as an emerging biogenic contaminant involved in chronic kidney diseases: A comprehensive review on exposure pathways, environmental health issues and future challenges

Cited by 23 publications

References 87 publications

Pharmacological mechanisms of Fuzheng Huayu formula for Aristolochic acid I–induced kidney fibrosis through network pharmacology

Pharmacological mechanisms of Fuzheng Huayu formula for Aristolochic acid I–induced kidney fibrosis through network pharmacology

Ethnomedical uses of Yawar Panga (<i>Aristolochia didyma</i>) in a therapeutic community dedicated to the treatment of drug addiction in the Peruvian Amazon

Uptake, Translocation, and Fate of Carcinogenic Aristolochic Acid in Typical Vegetables in Soil−Plant Systems

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