Study of the Cardiotoxicity of Venenum Bufonis in Rats using an 1H NMR-Based Metabolomics Approach

被引:91
作者
Dong, Ge [1 ]
Wei, Dandan [1 ]
Wang, Junsong [2 ]
Guo, Pingping [1 ]
Li, Minghui [2 ]
Yang, Minghua [1 ]
Kong, Lingyi [1 ]
机构
[1] China Pharmaceut Univ, Dept Nat Med Chem, State Key Lab Nat Med, Nanjing, Jiangsu, Peoples R China
[2] Nanjing Univ Sci & Technol, Ctr Mol Metab, Sch Environm & Biol Engn, Nanjing, Jiangsu, Peoples R China
基金
美国国家科学基金会;
关键词
TRADITIONAL CHINESE MEDICINE; TOAD VENOM; MASS-SPECTROMETRY; TOXICITY; BUFADIENOLIDES; METABONOMICS; SERUM; CHROMATOGRAPHY; THIOACETAMIDE; SPECTROSCOPY;
D O I
10.1371/journal.pone.0119515
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Venenum Bufonis, a well-known traditional Chinese medicine, has been widely used in Asia and has gained popularity in Western countries over the last decade. Venenum Bufonis has obvious side effects that have been observed in clinical settings, but few studies have reported on its cardiotoxicity. In this work, the cardiotoxicity of Venenum Bufonis was investigated using a H-11 NMR-based metabolomics approach. The H-1 NMR profiles of the serum, myocardial extracts and liver extracts of specific-pathogen-free rats showed that Venenum Bufonis produced significant metabolic perturbations dose-dependently with a distinct time effect, peaking at 2 hr after dosing and attenuating gradually. Clinical chemistry, electrocardiographic recordings, and histopathological evaluation provided additional evidence of Venenum Bufonis-induced cardiac damage that complemented and supported the metabolomics findings. The combined results demonstrated that oxidative stress, mitochondrial dysfunction, and energy metabolism perturbations were associated with the cardiac damage that results from Venenum Bufonis.
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页数:22
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