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- Publisher Website: 10.1007/s00204-021-03129-6
- Scopus: eid_2-s2.0-85112482129
- PMID: 34390356
- WOS: WOS:000684912200002
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Article: Developing urinary pyrrole–amino acid adducts as non-invasive biomarkers for identifying pyrrolizidine alkaloids-induced liver injury in human
Title | Developing urinary pyrrole–amino acid adducts as non-invasive biomarkers for identifying pyrrolizidine alkaloids-induced liver injury in human |
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Authors | |
Keywords | Biomarker Hepatotoxicity Non-invasive Pyrrole-amino acid adducts Pyrrolizidine alkaloids-induced liver injury |
Issue Date | 2021 |
Citation | Archives of Toxicology, 2021, v. 95, n. 10, p. 3191-3204 How to Cite? |
Abstract | Pyrrolizidine alkaloids (PAs) have been found in over 6000 plants worldwide and represent the most common hepatotoxic phytotoxins. Currently, a definitive diagnostic method for PA-induced liver injury (PA-ILI) is lacking. In the present study, using a newly developed analytical method, we identified four pyrrole-amino acid adducts (PAAAs), namely pyrrole-7-cysteine, pyrrole-9-cysteine, pyrrole-9-histidine, and pyrrole-7-acetylcysteine, which are generated from reactive pyrrolic metabolites of PAs, in the urine of PA-treated male Sprague Dawley rats and PA-ILI patients. The elimination profiles, abundance, and persistence of PAAAs were systematically investigated first in PA-treated rat models via oral administration of retrorsine at a single dose of 40 mg/kg and multiple doses of 5 mg/kg/day for 14 consecutive days, confirming that these urinary excreted PAAAs were derived specifically from PA exposure. Moreover, we determined that these PAAAs were detected in ~ 82% (129/158) of urine samples collected from ~ 91% (58/64) of PA-ILI patients with pyrrole-7-cysteine and pyrrole-9-histidine detectable in urine samples collected at 3 months or longer times after hospital admission, indicating adequate persistence time for use as a clinical test. As direct evidence of PA exposure, we propose that PAAAs can be used as a biomarker of PA exposure and the measurement of urinary PAAAs could be used as a non-invasive test assisting the definitive diagnosis of PA-ILI in patients. |
Persistent Identifier | http://hdl.handle.net/10722/342631 |
ISSN | 2023 Impact Factor: 4.8 2023 SCImago Journal Rankings: 1.236 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Zhu, Lin | - |
dc.contributor.author | Zhang, Chunyuan | - |
dc.contributor.author | Zhang, Wei | - |
dc.contributor.author | Xia, Qingsu | - |
dc.contributor.author | Ma, Jiang | - |
dc.contributor.author | He, Xin | - |
dc.contributor.author | He, Yisheng | - |
dc.contributor.author | Fu, Peter P. | - |
dc.contributor.author | Jia, Wei | - |
dc.contributor.author | Zhuge, Yuzheng | - |
dc.contributor.author | Lin, Ge | - |
dc.date.accessioned | 2024-04-17T07:05:09Z | - |
dc.date.available | 2024-04-17T07:05:09Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Archives of Toxicology, 2021, v. 95, n. 10, p. 3191-3204 | - |
dc.identifier.issn | 0340-5761 | - |
dc.identifier.uri | http://hdl.handle.net/10722/342631 | - |
dc.description.abstract | Pyrrolizidine alkaloids (PAs) have been found in over 6000 plants worldwide and represent the most common hepatotoxic phytotoxins. Currently, a definitive diagnostic method for PA-induced liver injury (PA-ILI) is lacking. In the present study, using a newly developed analytical method, we identified four pyrrole-amino acid adducts (PAAAs), namely pyrrole-7-cysteine, pyrrole-9-cysteine, pyrrole-9-histidine, and pyrrole-7-acetylcysteine, which are generated from reactive pyrrolic metabolites of PAs, in the urine of PA-treated male Sprague Dawley rats and PA-ILI patients. The elimination profiles, abundance, and persistence of PAAAs were systematically investigated first in PA-treated rat models via oral administration of retrorsine at a single dose of 40 mg/kg and multiple doses of 5 mg/kg/day for 14 consecutive days, confirming that these urinary excreted PAAAs were derived specifically from PA exposure. Moreover, we determined that these PAAAs were detected in ~ 82% (129/158) of urine samples collected from ~ 91% (58/64) of PA-ILI patients with pyrrole-7-cysteine and pyrrole-9-histidine detectable in urine samples collected at 3 months or longer times after hospital admission, indicating adequate persistence time for use as a clinical test. As direct evidence of PA exposure, we propose that PAAAs can be used as a biomarker of PA exposure and the measurement of urinary PAAAs could be used as a non-invasive test assisting the definitive diagnosis of PA-ILI in patients. | - |
dc.language | eng | - |
dc.relation.ispartof | Archives of Toxicology | - |
dc.subject | Biomarker | - |
dc.subject | Hepatotoxicity | - |
dc.subject | Non-invasive | - |
dc.subject | Pyrrole-amino acid adducts | - |
dc.subject | Pyrrolizidine alkaloids-induced liver injury | - |
dc.title | Developing urinary pyrrole–amino acid adducts as non-invasive biomarkers for identifying pyrrolizidine alkaloids-induced liver injury in human | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1007/s00204-021-03129-6 | - |
dc.identifier.pmid | 34390356 | - |
dc.identifier.scopus | eid_2-s2.0-85112482129 | - |
dc.identifier.volume | 95 | - |
dc.identifier.issue | 10 | - |
dc.identifier.spage | 3191 | - |
dc.identifier.epage | 3204 | - |
dc.identifier.eissn | 1432-0738 | - |
dc.identifier.isi | WOS:000684912200002 | - |