Urine metabolomics study on the liver injury in rats induced by raw and processed Polygonum multiflorum integrated with pattern recognition and pathways analysis

Zhang, Cong-En; Niu, Ming; Qi, Li; Yan, Zhao; Ma, Zhi-Jie; Xiong, Yin; Dong, Xiaoping; Li, Ruiyu; Feng, Wuwen; Dong, Qing; Ma, Xiao; Zhu, Yichao; Zou, Zhengsheng; Cao, Junling; Wang, Jiabo

doi:10.1016/j.jep.2016.09.011

Cited by 44 publications

(31 citation statements)

References 31 publications

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“…Clinical observations and the published PM‐DILI literature do not reveal any clustering characteristics of specific preparations or formulas of PM; PM‐DILI cases occur with the use of general preparations or formulas of PM. Additionally, our previous studies and published data showed that either PM or preparations containing PM could induce liver injury, but the concomitant components in the preparations and formulas did not . Thus, we consider the allele found in this study to be primarily associated with PM.…”

Section: Discussionsupporting

confidence: 54%

“…Recent studies have indicated that PM‐DILI might be an IDILI related to immune reaction . Previous studies have attempted to find biomarkers for the diagnosis and prevention of PM‐DILI by evaluating cytochrome 450 polymorphisms and metabolomics in various models. Unfortunately, no satisfactory biomarkers are currently available to identify human populations susceptible to this injury.…”

Section: Discussionmentioning

confidence: 99%

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HLA‐B*35:01 Allele Is a Potential Biomarker for Predicting Polygonum multiflorum–Induced Liver Injury in Humans

Rao

Chen

et al. 2019

Hepatology

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Polygonum multiflorum (PM) is a well‐known Chinese herbal medicine that has been reported to induce inflammation‐associated idiosyncratic liver injury. This study aimed to identify the genetic basis of susceptibility to PM‐drug‐induced liver injury (PM‐DILI) and to develop biological markers for predicting the risk of PM‐DILI in humans. The major histocompatibility complex (MHC) regions of 11 patients with PM‐DILI were sequenced, and all human leukocyte antigen (HLA)–type frequencies were compared to the Han‐MHC database. An independent replication study that included 15 patients with PM‐DILI, 33 patients with other DILI, and 99 population controls was performed to validate the candidate allele by HLA‐B PCR sequence‐based typing. A prospective cohort study that included 72 outpatients receiving PM for 4 weeks was designed to determine the influence of the risk allele on PM‐DILI. In the pilot study, the frequency of HLA‐B*35:01 was 45.4% in PM‐DILI patients compared with 2.7% in the Han Chinese population (odds ratio [OR], 30.4; 95% confidence interval [CI], 11.7‐77.8; P = 1.9 × 10−10). In the independent replication study and combined analyses, a logistic regression model confirmed that HLA‐B*35:01 is a high‐risk allele of PM‐DILI (PM‐DILI versus other DILI, OR, 86.5; 95% CI, 14.2‐527.8, P = 1.0 × 10−6; and PM‐DILI versus population controls, OR, 143.9; 95% CI, 30.1‐687.5, P = 4.8 × 10−10). In the prospective cohort study, an asymptomatic increase in transaminase levels was diagnosed in 6 patients, representing a significantly higher incidence (relative risk, 8.0; 95% CI, 1.9‐33.2; P < 0.02) in the HLA‐B*35:01 carriers (37.5%) than in the noncarriers (4.7%). Conclusion: The HLA‐B*35:01 allele is a genetic risk factor for PM‐DILI and a potential biomarker for predicting PM‐DILI in humans.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

HLA‐B*35:01 Allele Is a Potential Biomarker for Predicting Polygonum multiflorum–Induced Liver Injury in Humans

Rao

Chen

et al. 2019

Hepatology

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“…In accordance with the Trp level, 4-pyridoxic acid and salicylic acid were reduced in OG sheep in the current study. Lower levels of 4-pyridoxic acid reflect vitamin B6 dysfunction [43]. The active form of vitamin B6 is involved in various enzyme reactions that are related to amino acid and lipid metabolism [34].…”

Section: Discussionmentioning

confidence: 99%

Comparative metabolome analysis of serum changes in sheep under overgrazing or light grazing conditions

Zhang

Gao

Guo

et al. 2019

Preprint

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Background Overgrazing is a primary contributor to severe reduction in forage quality and production in Inner Mongolia, leading to extensive ecosystem degradation, sheep health impairment and growth performance reduction. Further studies to identify serum biomarkers that reflect changes in sheep health and nutritional status following overgrazing would be beneficial. We hereby hypothesize that reduced sheep growth performance under overgrazing conditions would be associated with metabolic and immune response alterations. This study used an untargeted metabolomics analysis by conducting ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) of sheep serum under overgrazing and light grazing conditions to identify metabolic disruptions in response to overgrazing. Results The sheep body weight gains as well as serum biochemical variables associated with immune responses and nutritional metabolism (immunoglobulin G, albumin, glucose, and nonesterified fatty acids) were significantly decreased with overgrazing compared with light grazing condition. In contrast, other serum parameters such as alanine and aspartate aminotransferase, alkaline phosphatase, total bilirubin, blood urea nitrogen, and interleukin-8 were markedly higher in the overgrazing group. Principal component analysis discriminated the metabolomes of the light grazing from the overgrazing group. Multivariate and univariate analyses revealed changes in the serum concentrations of 15 metabolites (9 metabolites exhibited a marked increase, whereas 6 metabolites showed a significant decrease) in the overgrazing group. Major changes of fatty acid oxidation, bile acid biosynthesis, and purine and protein metabolism were observed. Conclusions These findings offer metabolic evidence for putative biomarkers for overgrazing-induced changes in serum metabolism. Target-identification of these particular metabolites may potentially increase our knowledge of the molecular mechanisms of altered immune responses, nutritional metabolism, and reduced sheep growth performance under overgrazing conditions.

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“…Metabolomics is ideally positioned to address the challenges of toxicology in the twenty‐first century, as it provides accurate knowledge of disturbed biochemical pathways related to the extent of the toxic insult and its underlying mechanisms (Ramirez et al, ). For this reason, metabolomics has been widely applied in toxicological fields regarding both Western drugs and CMs, particularly to discover potential toxic biomarkers and elucidate the mechanisms of toxicity (Wang et al, ), including hepatotoxicity (Zhang et al, ), nephrotoxicity (Zhao & Lint, ), cardiotoxicity (Li et al, ) and reproductive toxicity (Huang et al, ). It was demonstrated that metabolomics could better reflect the growth and development of an embryo than the use of traditional morphology methods, particularly in pregnancy (Vergouw et al, ).…”

Section: Amniotic Fluid Metabolomicsmentioning

confidence: 99%

Metabolomics of the amniotic fluid: Is it a feasible approach to evaluate the safety of Chinese medicine during pregnancy?

Shan

Xie

Zhou

et al. 2018

J of Applied Toxicology

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The use of Chinese medicines (CMs) during pregnancy has long been a major public health concern. Although CMs have been shown to be effective in treating infertility and preventing miscarriage, their use has been restricted, mainly because of limited knowledge of their potential toxicity. Accurate toxicology data are urgently required to assess whether these CMs are safe for maternal health and fetal development. Amniotic fluid (AF) contains carbohydrates, lipids and phospholipids, urea and proteins, all of which aid in the growth of the fetus and reflect the mother's health status as well. The changes in metabolomic patterns of AF are related to pathophysiological occurrences during the course of pregnancy. In this review, we provide a summary of the research performed in recent years on metabolomic AF samples, and use our previous study as an example to explore the feasibility of metabolomics of AF to evaluate the safety of CMs during pregnancy. We believe that metabolomics of AF play a far more important role than traditional morphology methods in the safety evaluation of CMs for pregnancy, with a higher sensitivity and correlation.

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Urine metabolomics study on the liver injury in rats induced by raw and processed Polygonum multiflorum integrated with pattern recognition and pathways analysis

Cited by 44 publications

References 31 publications

HLA‐B*35:01 Allele Is a Potential Biomarker for Predicting Polygonum multiflorum–Induced Liver Injury in Humans

HLA‐B*35:01 Allele Is a Potential Biomarker for Predicting Polygonum multiflorum–Induced Liver Injury in Humans

Comparative metabolome analysis of serum changes in sheep under overgrazing or light grazing conditions

Metabolomics of the amniotic fluid: Is it a feasible approach to evaluate the safety of Chinese medicine during pregnancy?

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