127191-86-0

Usage

Uses

Used in Toxicology Research:
7-(deoxyadenosin-N(6)-yl)aristolactam I is used as a subject of study in toxicology research for understanding its role in the development of aristolochic acid-induced nephropathy and upper urinary tract carcinomas. The research aims to investigate the mechanisms of its genotoxicity and its potential as a biomarker for exposure to aristolochic acid.
Used in Regulatory and Safety Assessments:
dA-AL-I is utilized in regulatory and safety assessments to evaluate the risks associated with the presence of aristolochic acid in plants and herbal remedies. This helps in establishing guidelines and restrictions on the use of such substances to protect public health.
Used in Development of Detection Methods:
7-(deoxyadenosin-N(6)-yl)aristolactam I is used in the development of detection methods to identify and quantify the presence of aristolochic acid in various products. These methods are crucial for ensuring the safety and quality of herbal remedies and food products.
Used in Education and Awareness Programs:
dA-AL-I serves as a key component in educational and awareness programs aimed at informing the public and healthcare professionals about the potential risks of aristolochic acid exposure. This helps in promoting safer practices and avoiding the use of harmful substances in traditional medicine and supplements.

InChI:InChI=1/C27H22N6O7/c1-37-14-4-2-3-11-18(14)21(22-19-12(27(36)32-22)5-15-24(20(11)19)39-10-38-15)31-25-23-26(29-8-28-25)33(9-30-23)17-6-13(35)16(7-34)40-17/h2-5,8-9,13,16-17,34-35H,6-7,10H2,1H3,(H,32,36)(H,28,29,31)

Upstream product

• 313-67-7 aristolochic acid I 
• 958-09-8 2'-deoxy-D-adenosine 

Relevant academic research and scientific papers

Comparison of Aristolochic acid I derived DNA adduct levels in human renal toxicity models

Aristolochic acid (AA) dependent human nephropathy results either from environmental exposure to Aristolochiaceae plant subspecies or their use in traditional phytotherapy. The toxic components are structurally related nitrophenanthrene carboxylic acids, i.e. Aristolochic acid I (AAI) and II (AAII). AAI is considered to be the major cause of Aristolochic acid nephropathy, characterized by severe renal fibrosis and upper urothelial cancer. Following enzymatic activation in kidney and/or liver, AAI metabolites react with genomic DNA to form persistent DNA adducts with purines. To determine whether AAI can be activated in human renal cells to form DNA adducts, we exposed telomerase immortalized renal proximal tubular epithelial cells (RPTEC/TERT1), the human embryonic kidney (HEK293) cell line, as well as primary human kidney cells (pHKC) to AAI in vitro. We modified an isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (ID-UPLC-MS/MS) based method for the quantification of dA-AAI adducts in genomic DNA. In addition, time dependent accumulation of adducts in renal cortex and bladder tissue from AAI/II treated Eker rats were used to validate the detection method. AAI-induced toxicity in human renal cells was determined by dA-AAI adduct quantification, the impact on cell viability, and NQO1 expression and activity. Our findings demonstrated adduct formation in all cell lines, although only pHKC and RPTEC/TERT1 expressed NQO1. The highest adduct formation was detected in pHKC despite low NQO1 expression, while we observed much lower adduct levels in NQO1-negative HEK293 cells. Adduct formation and decreased cell viability correlated only weakly. Therefore, our data suggested that i.) enzymes other than NQO1 could be at least equally important for AA bioactivation in human renal proximal tubule cells, and ii.) the suggested correlation between adduct levels and viability appears to be questionable.