Application of UPLC-QTOF-MS in Analysis of Non-targeted Urine Metabolomics in Rats with Yunaconitine Poisoning

doi:10.12116/j.issn.1004-5619.2020.301003

Abstract

Abstract: Objective

To explore the possible mechanism of Yunaconitine poisoning by studying the changes of urine metabolic profile in rats chronically poisoned by Yunaconitine via non-targeted metabolomics.

Methods

A rat model of Yunaconitine poisoning was established, and a metabolomics method based on UPLC-QTOF-MS technology was used to obtain the urine metabolic profile. Principal component analysis （PCA）, orthogonal projections to latent structures-discriminant analysis （OPLS-DA）, variable importance in projection （VIP） value greater than 1, fold change （FC） value greater than 3 or less than 0.33 and P value less than 0.05 were used to screen potential biomarkers related to the toxicity of Yunaconitine. The metabolic pathway analysis was performed through the MetaboAnalyst website and pathological changes of related tissues were observed.

Results

Sixteen potential biomarkers including L-isoleucine were screened, which mainly involved six metabolic pathways including the biosynthesis and degradation of valine, leucine and isoleucine, pentose and glucuronate interconversions, and propanoate metabolism, alanine, aspartate and glutamate metabolism, tyrosine metabolism. Pathological studies showed that rat toxic change in nervous system, liver and cardiac caused by Yunaconitine.

Conclusion

Yunaconitine may cause neurotoxicity, hepatotoxicity and cardiotoxicity by affecting amino acid and glucose metabolism.

Key words: forensic toxicology, metabolomics, poisoning, Yunaconitine, ultra performance liquid chromatography coupled with quadrupole-time of flight-mass spectrometry, urine, rats

CLC Number:

DF795.1

Hui-xia ZHOU, Huan LIU, Xue HAN, Sheng-jie NIE, Rong-ping ZHANG, Jian-yun YU, Shu-hua LI. Application of UPLC-QTOF-MS in Analysis of Non-targeted Urine Metabolomics in Rats with Yunaconitine Poisoning[J]. Journal of Forensic Medicine, 2021, 37(5): 653-660.

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URL: http://www.fyxzz.cn/EN/10.12116/j.issn.1004-5619.2020.301003

http://www.fyxzz.cn/EN/Y2021/V37/I5/653

Figures/Tables 8

References 18

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序号	生物学标志物	相对分子质量	分子式	FC_橄榄油	FC_稀盐酸
1	L-异亮氨酸	131.09	C₆H₁₃NO₂	5.15	11.82
2	羟基异己二酸	132.08	C₆H₁₂O₃	11.69	18.19
3	甲基丙二酸	118.03	C₄H₆O₄	3.48	5.63
4	腺苷琥珀酸	463.07	C₁₄H₁₈N₅O₁₁P	4.34	3.30
5	N-乙酰基-D-苯丙氨酸	207.23	C₁₁H₁₃NO₃	4.01	3.42
6	3-甲氧基酪胺	167.09	C₉H₁₃NO₂	4.94	3.54
7	D-木糖	150.05	C₅H₁₀O₅	3.08	4.08
8	2-C-甲基-D-赤藓糖醇2，4-环二磷酸酯	278.09	C₅H₁₂O₉P₂	0.29	0.33
9	6-磷酸-D-山梨醇	262.15	C₆H₁₅O₉P	0.18	0.28
10	酵母氨酸	276.29	C₁₁H₂₀N₂O₆	8.23	7.40
11	丙酸	70.01	C₃H₂O₂	3.51	3.10
12	尿囊素	158.04	C₄H₆N₄O₃	8.94	18.90
13	N-乙酰基-DL-甲硫氨酸	191.25	C₇H₁₃NO₃S	3.37	6.22
14	4-硝基喹啉-1-氧化物	190.16	C₉H₆N₂O₃	3.58	6.03
15	二氢硫辛酸酯	208.06	C₈H₁₆O₂S₂	9.31	3.55
16	硫酸吲哚酚	213.01	C₈H₇NO₄S	5.63	4.50

序号	生物学标志物	相对分子质量	分子式	FC_橄榄油	FC_稀盐酸
1	L-异亮氨酸	131.09	C₆H₁₃NO₂	5.15	11.82
2	羟基异己二酸	132.08	C₆H₁₂O₃	11.69	18.19
3	甲基丙二酸	118.03	C₄H₆O₄	3.48	5.63
4	腺苷琥珀酸	463.07	C₁₄H₁₈N₅O₁₁P	4.34	3.30
5	N-乙酰基-D-苯丙氨酸	207.23	C₁₁H₁₃NO₃	4.01	3.42
6	3-甲氧基酪胺	167.09	C₉H₁₃NO₂	4.94	3.54
7	D-木糖	150.05	C₅H₁₀O₅	3.08	4.08
8	2-C-甲基-D-赤藓糖醇2，4-环二磷酸酯	278.09	C₅H₁₂O₉P₂	0.29	0.33
9	6-磷酸-D-山梨醇	262.15	C₆H₁₅O₉P	0.18	0.28
10	酵母氨酸	276.29	C₁₁H₂₀N₂O₆	8.23	7.40
11	丙酸	70.01	C₃H₂O₂	3.51	3.10
12	尿囊素	158.04	C₄H₆N₄O₃	8.94	18.90
13	N-乙酰基-DL-甲硫氨酸	191.25	C₇H₁₃NO₃S	3.37	6.22
14	4-硝基喹啉-1-氧化物	190.16	C₉H₆N₂O₃	3.58	6.03
15	二氢硫辛酸酯	208.06	C₈H₁₆O₂S₂	9.31	3.55
16	硫酸吲哚酚	213.01	C₈H₇NO₄S	5.63	4.50

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