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

• Published in: PloS one Vol. 10; no. 3; p. e0119515
• Main Authors: Dong, Ge, Wei, Dandan, Wang, Junsong, Guo, Pingping, Li, Minghui, Yang, Minghua, Kong, Lingyi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.03.2015; Public Library of Science (PLoS)
• Subjects: Amino acids; Animals; Bioengineering; Biomarkers; Bufanolides - toxicity; Cardiotoxicity; Cardiotoxins - toxicity; Chemistry; Chinese medicine; Damage assessment; Dose-Response Relationship, Drug; Energy metabolism; Experiments; Heart; Heart diseases; Herbal medicine; Laboratory animals; Liver; Magnetic Resonance Spectroscopy; Male; Metabolism; Metabolites; Metabolome - drug effects; Metabolomics; Mitochondria; Myocardium - metabolism; Myocardium - pathology; NMR; Nuclear magnetic resonance; Oxidative stress; Pharmaceutical sciences; Rats; Rodents; Side effects; Toxicity; Traditional Chinese medicine; Urine; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0119515

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 11H NMR-based metabolomics approach. The 1H 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.