Metabolomic approach for the identification of therapeutic targets of erythropoietin against sepsis in rat models

X. Shi, F. Yang, Y.-N. Zheng, H. Zhang, X.-X. Wang, G.-J. Shao, X.-L. Lai

Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai, China. shaoguojian_wz@163.com

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• Pharmacology

OBJECTIVE: Owing to a lack of effective treatment approaches, sepsis is considered a life-threatening clinical syndrome worldwide. Many therapeutic interventions combating sepsis have been evaluated in animal models and clinical cases over the past few decades. Due to the pleiotropic characteristics of EPO, many studies have shown that erythropoietin (EPO) would be used to alleviate sepsis-induced tissue injury beyond the hemoglobin elevation effect. Nevertheless, the organ protective activity of EPO could not be supported by all of the results. In order to address the unanswered questions, a new methodical approach is necessary to be considered. The latest progress in metabolomics could be helpful to interpret the underlying mechanisms of EPO on sepsis, via metabolite profiling, to bring in some potent predictable fact for clinical application.

MATERIALS AND METHODS: Twenty-one male Sprague-Dawley rats were divided into 3 groups of 7 rats each. Sepsis was induced by cecal ligation and puncture (CLP). Rats in the sepsis group were injected with equal volume of saline post-CLP. Rats from the EPO group were treated twice with EPO (immediately and 24 hours after CLP, 3750 IU/kg). The rats in the sham group were subjected to a sham surgery and injected with saline at the same time as the sepsis group. Serum samples were collected for biochemical and metabolomic analysis 72 hours post-CLP.

RESULTS: Biochemistry analysis revealed that erythropoietin improved the condition of multiple organs damaged by sepsis. Fifty-eight serum metabolites, including amino acids and fatty acids, displayed significant differences between the sepsis and sham groups. EPO treatment was found to attenuate the metabolic imbalances induced by CLP.

CONCLUSIONS: This study indicated that the metabolomic approach provided a comprehensive insight towards the metabolic targets of EPO treatment of sepsis.

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