Simultaneous toxicokinetic studies of aristolochic acid I and II and aristolactam I and II using a newly-developed microdialysis liquid chromatography-tandem mass spectrometry

Su-Yin Chiang; Ming-Tsai Wey; Yu-Syuan Luo; Wei-Chung Shih; Dalaijamts Chimeddulam; Po-Chi Hsu; Hui-Fen Huang; Tung-Hu Tsai; Kuen-Yuh Wu

doi:10.1016/j.fct.2023.113856

Simultaneous toxicokinetic studies of aristolochic acid I and II and aristolactam I and II using a newly-developed microdialysis liquid chromatography-tandem mass spectrometry

Food Chem Toxicol. 2023 Jul:177:113856. doi: 10.1016/j.fct.2023.113856. Epub 2023 May 29.

Authors

Su-Yin Chiang¹, Ming-Tsai Wey², Yu-Syuan Luo³, Wei-Chung Shih², Dalaijamts Chimeddulam², Po-Chi Hsu¹, Hui-Fen Huang⁴, Tung-Hu Tsai⁵, Kuen-Yuh Wu⁶

Affiliations

¹ School of Chinese Medicine, College of Chinese Medicine, China Medical University, No. 91, Hsueh-Shih Rd, North Dist., Taichung, 404333, Taiwan.
² Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Zhongzheng Dist., Taipei, 100025, Taiwan.
³ Institute of Food and Health, College of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Zhongzheng Dist., Taipei, 404333, Taiwan.
⁴ School of Post-baccalaureate Chinese Medicine, Tzu Chi University, Hualien, 97004, Taiwan.
⁵ Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2. Linong St., Taipei, 100147, Taiwan.
⁶ Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Zhongzheng Dist., Taipei, 100025, Taiwan; Institute of Food and Health, College of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Zhongzheng Dist., Taipei, 404333, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Zhongzheng Dist., Taipei, 100025, Taiwan. Electronic address: kuenyuhwu@ntu.edu.tw.

PMID: 37257633
DOI: 10.1016/j.fct.2023.113856

Abstract

Aristolochic acids (AAs) are naturally occurring genotoxic carcinogens linked to Balkan endemic nephropathy and aristolochic acid nephropathy. Aristolochic acid I and II (AA-I and AA-II) are the most abundant AAs, and AA-I has been reported to be more genotoxic and nephrotoxic than AA-II. This study aimed to explore metabolic differences underlying the differential toxicity. We developed a novel microdialysis sampling coupled with solid-phase extraction liquid chromatography-tandem mass spectrometry (MD-SPE-LC-MS/MS) to simultaneously study the toxicokinetics (TK) of AA-I and AA-II and their corresponding aristolactams (AL-I and AL-II) in the blood of Sprague Dawley rats co-treated with AA-1 and AA-II. Near real-time monitoring of these analytes in the blood of treated rats revealed that AA-I was absorbed, distributed, and eliminated more rapidly than AA-II. Moreover, the metabolism efficiency of AA-I to AL-I was higher compared to AA-II to AL-II. Only 0.58% of AA-I and 0.084% of AA-II was reduced to AL-I and AL-II, respectively. The findings are consistent with previous studies and support the contention that differences in the in vivo metabolism of AA-I and AA-II may be critical factors for their differential toxicities.

Keywords: Aristolactam; Aristolochic acid; Balkan endemic nephropathy; In vivo microdialysis; Liquid chromatography-tandem mass spectrometry; Toxicokinetics.

MeSH terms

Animals
Aristolochic Acids* / chemistry
Aristolochic Acids* / toxicity
Balkan Nephropathy*
Chromatography, Liquid / methods
Kidney Diseases*
Microdialysis
Rats
Rats, Sprague-Dawley
Tandem Mass Spectrometry / methods
Toxicokinetics

Substances

aristolochic acid I
aristolactam I
Aristolochic Acids