Serum metabolomics of Bama miniature pigs bitten by Bungarus multicinctus

Zhi Huang; Meng Zhang; Dongling He; Pengshu Song; Caifeng Mo; Xiaoyang Cheng; Tianlin Song; Yalan Li; Xuerong Zhang; Ming Liao

doi:10.1016/j.toxlet.2021.07.017

Serum metabolomics of Bama miniature pigs bitten by Bungarus multicinctus

Toxicol Lett. 2021 Oct 10:350:225-239. doi: 10.1016/j.toxlet.2021.07.017. Epub 2021 Jul 31.

Authors

Zhi Huang¹, Meng Zhang², Dongling He³, Pengshu Song⁴, Caifeng Mo³, Xiaoyang Cheng³, Tianlin Song³, Yalan Li³, Xuerong Zhang³, Ming Liao⁵

Affiliations

¹ Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, PR China; Guangxi Medical University, Nanning, 530021, PR China.
² The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China.
³ Guangxi Medical University, Nanning, 530021, PR China.
⁴ Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, 530003, PR China.
⁵ Guangxi Medical University, Nanning, 530021, PR China. Electronic address: liaominggx@126.com.

PMID: 34343594
DOI: 10.1016/j.toxlet.2021.07.017

Abstract

Bungarus multicinctus is one of the top ten venomous snakes in China, and its bite causes acute and severe diseases, but its pathophysiology remains poorly elucidated. Thus, an animal model of Bungarus multicinctus bite was established by intramuscular injection of 30μg/kg of Bungarus multicinctus venom, and then the serum metabolites were subsequently screened, identified and validated by ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) methods to explore the potential biomakers and possible metabolic pathways. Untargeted metabolomics analysis showed that 36 and 38 endogenous metabolites levels changed in ESI+ and ESI-, respectively, KEGG pathway analysis showed that 5 metabolic pathways, including mineral absorption, central carbon metabolism in cancer, protein digestion and absorption, aminoacyl-tRNA biosynthesis and ABC transporters might be closely related to Bungarus multicinctus bite. Targeted metabolomics analysis showed that there were significant differences in serum D-proline, L-leucine and L-glutamine after Bungarus multicinctus bite (P < 0.05). In addition, receiver operating characteristic (ROC) analysis showed that the diagnostic efficiency of L-Glutamine was superior to other potential biomarkers and the AUC value was 0.944. Moreover, we found evidence for differences in the pathophysiology of glutamine between Bungarus multicinctus bite group and normal group, specifically with the content of glutamine synthetase (GS) and glutaminase (GLS). Taken together, the current study has successfully established an animal model of Bungarus multicinctus bite, and further identified the links between the metabolic perturbations and the pathophysiology and the potential diagnostic biomakers of Bungarus multicinctus bite, which provided valuable insights for studying the mechanism of Bungarus multicinctus bite.

Keywords: Bama miniature pigs; Bungarus multicinctus bite; Metabolic pathways; Metabolites; Metabolomics.

MeSH terms

Animals
Bungarus*
China
Elapid Venoms / blood*
Elapid Venoms / metabolism*
Elapid Venoms / toxicity*
Female
Male
Metabolic Networks and Pathways / drug effects*
Metabolomics*
Mice
Models, Animal
Swine
Swine, Miniature / blood*

Substances

Elapid Venoms