Time-resolved metabolomics analysis of individual differences during the early stage of lipopolysaccharide-treated rats.
Lipopolysaccharide (LPS) can lead to uncontrollable cytokine production and eventually cause fatal sepsis syndrome. Individual toxicity difference of LPS has been widely reported. In our study we observed that two thirds of the rats (24/36) died at a given dose of LPS, while the rest (12/36) survived. Tracking the dynamic metabolic change in survival and non-survival rats in the early stage may reveal new system information to understand the inter-individual variation in response to LPS. As the time-resolved datasets are very complex and no single method can elucidate the problem clearly and comprehensively, the static and dynamic metabolomics methods were employed in combination as cross-validation. Intriguingly, some common results have been observed. Lipids were the main different metabolites between survival and non-survival rats in pre-dose serum and in the early stage of infection with LPS. The LPS treatment led to S-adenosly-methionine and total cysteine individual difference in early stage, and subsequent significant perturbations in energy metabolism and oxidative stress. Furthermore, cytokine profiles were analyzed to identify potential biological associations between cytokines and specific metabolites. Our collective findings may provide some heuristic guidance for elucidating the underlying mechanism of individual difference in LPS-mediated disease.
Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Die
D
Dai
Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Yiqiao
Y
Gao
Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Jiaqing
J
Chen
Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Yin
Y
Huang
Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.|State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China.
Zunjian
Z
Zhang
Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.|State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China.
Fengguo
F
Xu
D000818:Animals; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides
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