Metabolic Changes in Paraquat Poisoned Patients and Support Vector Machine Model of Discrimination

Wang, Xianqin; Zhang, Meiling; Ma, Jianshe; Zhang, Yuan; Hong, Guangliang; Sun, Fa; Lin, Gen‐Min; Hu, Lufeng

doi:10.1248/bpb.b14-00781

Cited by 36 publications

(34 citation statements)

References 22 publications

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“…Since Wang et al [44] reported that the plasma levels of cholesterol significantly increased in PQ poisoned patients in comparison to healthy volunteers, we hypothesize that PQ toxicity may also be associated with the changes of cholesterol metabolism. Considerable evidence indicates that LXRs are crucial regulators of cholesterol metabolism and play an important role in the pathway of reverse cholesterol transport, in which excess cholesterol is transported in high-density lipoprotein (HDL) particles from peripheral cells to the liver for excretion in bile [45].…”

Section: Discussionmentioning

confidence: 85%

Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-κB and JNK/p38 MAPK Signal Pathways

Shen

Wang

et al. 2017

BioMed Research International

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Paraquat (PQ) is a widely used herbicide with extremely high poisoning mortality mostly from acute lung injury (ALI) or progressive pulmonary fibrosis. Toxicity mechanisms remain unclear, but a redox cycling process that generates reactive oxygen species (ROS) is involved, as are inflammation and cell apoptosis. We established an ALI mouse model by intraperitoneal injection of PQ (28 mg/kg) and then investigated the effects of a potent liver X receptor (LXR) agonist, TO901317 (5 or 20 mg/kg), injected intraperitoneally 30 min after PQ administration. Poisoned mice exhibited severe lung tissue lesions and edema, significant neutrophilic (PMNs) infiltration, and release of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). PQ administration also decreased activity of antioxidases, including superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferases (GSTs), and increased lipid peroxidation as evaluated by malondialdehyde (MDA) levels. PQ exposure induced upregulation of the proapoptotic gene Bax and downregulation of the antiapoptotic gene Bcl-2, leading to marked cell apoptosis in the lung tissues. TO901317 treatment reversed all these effects through inhibition of PQ-induced nuclear factor kappa B (NF-κB) and JNK/p38 mitogen-activated protein kinase (MAPK) activation. The LXR agonist TO901317 had potent antioxidant, anti-inflammatory, and antiapoptotic effects against PQ-induced ALI.

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Section: Discussionmentioning

confidence: 85%

Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-κB and JNK/p38 MAPK Signal Pathways

Shen

Wang

et al. 2017

BioMed Research International

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“…, determinate coefficient; HCT, hematocrit; PLT, blood platelet; HB, hemoglobin; RBCVD, red blood cell volume distribution; THR, thrombocytocrit; MPL, mean platelet volume; AVM, absolute value of monocyte; MCH, mean corpuscular hemoglobin; PLC, percentage of leukomonocyte. study, this prediction model may be developed in further studies, such as back-propagation artificial neural network (19) and extreme learning machine (10) models, and support vector machine (20) to improved predictive capabilities.…”

Section: Discussionmentioning

confidence: 99%

Association of blood glucose and lipid levels with complete blood count indices to establish a regression model

et al. 2017

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Abstract. Hyperglycemia and hyperlipidemia, which are usually diagnosed by analysis of blood glucose (GLU) and lipid levels, are two of the most common diseases in modern society. The purpose of the current study was to investigate the potential association between blood GLU and lipid levels with complete blood count (CBC) indices in overweight and healthy individuals and establish a regression model. There were 456 healthy and 421 overweight participants in the study. Data were collected on triglyceride (TG), total cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood GLU and CBC. The distribution characteristics and differences between healthy and overweight subjects were analyzed. Subsequently, the associations between TG, CHO, HDL, LDL and GLU with CBC were analyzed using correlation analysis and multiple linear regression (MLR). Significant differences were identified between the healthy and overweight individuals in TG, CHO, HDL, LDL, GLU and in the majority of the CBC indices. The correlation analysis indicated that there were strong correlations between TG, LDL, HDL, CHO and GLU with CBC indices in the healthy and overweight subjects. The MLR demonstrated that the regression models of TG, LDL, HDL and CHO, but no GLU, were statistically significant in the two groups (P<0.001). The HDL regression model exhibited the best regression parameters; the multiple correlation coefficients (R) were 0.351 and 0.308 in the healthy and overweight subjects, respectively. In the overweight and healthy subjects, there were strong correlations between TG, LDL, HDL and CHO with CBC indices, with HDL being the most relevant to the CBC indices. The CBC demonstrated statistical significance in the diagnosis of hyperlipidemia.

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“…MS detection was conducted in EI mode with electron energy of 70 eV, and then in full-scan mode with m/z of 50-550 by splitless mode injection. Detailed information on the procedure has been published previously [16,17]. …”

Section: Methodsmentioning

confidence: 99%

Fisher Discrimination of Metabolic Changes in Rats Treated with Aspirin and Ibuprofen

Zhang

Song²,

Jiang³

et al. 2017

Pharmacology

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Background: Aspirin and ibuprofen are the most frequently prescribed non-steroidal anti-inflammatory drugs in the world. However, both are associated with a variety of toxicities. We applied serum metabonomics and Fisher discrimination for the early diagnosis of its toxic reaction in order to help diagnose these toxicities. Methods: A total of 45 rats were randomly divided into Control group, Aspirin group, and Ibuprofen groups. The experiment groups were given intragastric aspirin (15 mg/kg) or ibuprofen (15 mg/kg) for 3 weeks. Liver function tests were performed and blood metabonomics were analyzed by gas chromatography-mass spectrometry. Results: The most important compounds altered were trihydroxybutyric acid and l-alanine in the aspirin group, and acetoacetic acid, l-alanine, and trihydroxybutyric acid in the ibuprofen group. With respect to metabolic profiles, all 3 groups were completely distinct from one another. Fisher discrimination showed that 91.1% of the original grouped cases were correctly classified by the third week. However, only 55.6% of liver function tests were able to classify grouped cases correctly. Conclusion: Trihydroxybutyric acid, l-alanine, and acetoacetic acid were the most significant indicators of altered serum metabolites following intragastric administration of aspirin and ibuprofen in rates. These metabolomic data may be used for classification of aspirin and ibuprofen toxicity.

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Metabolic Changes in Paraquat Poisoned Patients and Support Vector Machine Model of Discrimination

Cited by 36 publications

References 22 publications

Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-κB and JNK/p38 MAPK Signal Pathways

Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-κB and JNK/p38 MAPK Signal Pathways

Association of blood glucose and lipid levels with complete blood count indices to establish a regression model

Fisher Discrimination of Metabolic Changes in Rats Treated with Aspirin and Ibuprofen

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