Biotransformation and Toxicities of Aristolochic Acids

Sidorenko, Viktoriya S.

doi:10.1007/978-3-030-41283-8_9

Cited by 12 publications

(7 citation statements)

References 163 publications

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“…While various modes of toxicities of AA have recently been extensively reviewed, 51 the study presented here identifies specific and complex mRNA:miRNA networks of the AAN‐associated UTUC, supported by adduct analysis, with components of key affected pathways further validated by high‐throughput tissue microarray immunohistochemistry. Sequencing of patient exomes and transcriptomes confirmed a burden of somatic A:T>T:A transversions in UTUC and provided insights into deleteriously mutated expressed genes.…”

Section: Discussionmentioning

confidence: 91%

Molecular profiles and urinary biomarkers of upper tract urothelial carcinomas associated with aristolochic acid exposure

Karanović

Ardin

Tang

et al. 2021

Intl Journal of Cancer

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Recurrent upper tract urothelial carcinomas (UTUCs) arise in the context of nephropathy linked to exposure to the herbal carcinogen aristolochic acid (AA). Here we delineated the molecular programs underlying UTUC tumorigenesis in patients from endemic aristolochic acid nephropathy (AAN) regions in Southern Europe. We applied an integrative multiomics analysis of UTUCs, corresponding unaffected tissues and of patient urines. Quantitative microRNA (miRNA) and messenger ribonucleic acid (mRNA) expression profiling, immunohistochemical analysis by tissue microarrays and exome and transcriptome sequencing were performed in UTUC and nontumor tissues. Urinary miRNAs of cases undergoing surgery were profiled before and after tumor resection. Ribonucleic acid (RNA) and protein levels were analyzed using appropriate statistical tests and trend assessment. Dedicated bioinformatic tools were used for analysis of pathways, mutational signatures and result visualization. The results delineate UTUC‐specific miRNA:mRNA networks comprising 89 miRNAs associated with 1,862 target mRNAs, involving deregulation of cell cycle, deoxyribonucleic acid (DNA) damage response, DNA repair, bladder cancer, oncogenes, tumor suppressors, chromatin structure regulators and developmental signaling pathways. Key UTUC‐specific transcripts were confirmed at the protein level. Exome and transcriptome sequencing of UTUCs revealed AA‐specific mutational signature SBS22, with 68% to 76% AA‐specific, deleterious mutations propagated at the transcript level, a possible basis for neoantigen formation and immunotherapy targeting. We next identified a signature of UTUC‐specific miRNAs consistently more abundant in the patients' urine prior to tumor resection, thereby defining biomarkers of tumor presence. The complex gene regulation programs of AAN‐associated UTUC tumors involve regulatory miRNAs prospectively applicable to noninvasive urine‐based screening of AAN patients for cancer presence and recurrence.

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Section: Discussionmentioning

confidence: 91%

Molecular profiles and urinary biomarkers of upper tract urothelial carcinomas associated with aristolochic acid exposure

Karanović

Ardin

Tang

et al. 2021

Intl Journal of Cancer

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“…While mitochondria are the sole major source of reactive oxygen species (ROS) in animal cells, chloroplasts generate an abundant additional ROS flow in plants [9,10]. Last, but not least, plants produce a wide variety of genotoxic secondary metabolites, of which psoralens, topoisomerase inhibitors (camptothecins, podophyllotoxins), and aristolochic acid are probably the best-studied examples [11][12][13][14][15]. Moreover, some widespread plant protein toxins, such as ribosome-inactivating proteins, also damage DNA on top of their primary mode of action [16].…”

Section: Dna Damage Specifics In Plantsmentioning

confidence: 99%

Base Excision DNA Repair in Plants: Arabidopsis and Beyond

Grin,

Petrova,

Endutkin

et al. 2023

IJMS

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Base excision DNA repair (BER) is a key pathway safeguarding the genome of all living organisms from damage caused by both intrinsic and environmental factors. Most present knowledge about BER comes from studies of human cells, E. coli, and yeast. Plants may be under an even heavier DNA damage threat from abiotic stress, reactive oxygen species leaking from the photosynthetic system, and reactive secondary metabolites. In general, BER in plant species is similar to that in humans and model organisms, but several important details are specific to plants. Here, we review the current state of knowledge about BER in plants, with special attention paid to its unique features, such as the existence of active epigenetic demethylation based on the BER machinery, the unexplained diversity of alkylation damage repair enzymes, and the differences in the processing of abasic sites that appear either spontaneously or are generated as BER intermediates. Understanding the biochemistry of plant DNA repair, especially in species other than the Arabidopsis model, is important for future efforts to develop new crop varieties.

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“…UM medicines are available in powder and boluses forms and preparing with honey [2]. Recently, UM formula is removed Aristolochia stem due to toxicity and carcinogenicity of aristolochic acid contained [3,4]. Three herbal ingredients, chebulic myrobalan, beleric myrobalan and Indian gooseberry fruits are similar to Indian and Thai Ayurveda formula or "Triphala", which commonly treatment various chronic diseases, such as cardiovascular disease, hypertension, lipidaemia, liver diseases, asthma, intestinal inflammation and chronic ulcer.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Biological Activities From Thai Herbal Lozenges

2022

pnr

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UM-MA-RUEK-KA-VA-TEE (UM) is multi-herbal formula as antitussive and expectorant. New UM formula was prepared in lozenge for simply use. The research was proposed to evaluate bioactive constituents and biological activities of lozenge herbal mixture, including liquorice root, Indian gooseberry, coriander seed, gall of chebulic myrobalans, cumin, belleric myrobalan and karanda fruit. Phenolic, flavonoid and saponin contents were determined by spectrophotometric methods. Antioxidant activity was evaluated by DPPH and NO radical scavenging and reduction of lipid peroxidation. Anti-inflammation was evaluated by inhibition of albumin degradation and NO production of LPS-induced macrophages. Cytotoxicity was evaluated against human dermal fibroblasts. Herbal mixture (10%) and other ingredients was performed to lozenge. Reduction of oral microbials was determined in healthy volunteers (N = 30) before and after use lozenges by a modified dip-slide test. Total phenolic, total flavonoid and saponin contents were 188.34±2.96 mg of GAE/g, 19.24±1.59 mg of QE/g and 534.80±34.18 mg of SE/g, respectively. Herbal mixture was strongly inhibited DPPH and NO radicals, and potently reduced NO production from macrophages and without cytotoxicity. Oral microbials, including Mutans streptococci and Candida sp. were significantly decreased after lozenge use. New UM formula was contained saponins as most bioactive compound, and antioxidant, antiinflammation and anti-microbial activities was preferable.

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Biotransformation and Toxicities of Aristolochic Acids

Cited by 12 publications

References 163 publications

Molecular profiles and urinary biomarkers of upper tract urothelial carcinomas associated with aristolochic acid exposure

Molecular profiles and urinary biomarkers of upper tract urothelial carcinomas associated with aristolochic acid exposure

Base Excision DNA Repair in Plants: Arabidopsis and Beyond

Evaluation of Biological Activities From Thai Herbal Lozenges

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