Metabonomic approaches investigate diosbulbin B-induced pulmonary toxicity and elucidate its underling mechanism in male mice

Autor: Naining Song, Haishan Li, Hainan Ji, Chan Zhao, Baoliang Xu, Chang Liu, Na Tong, Hua Li, Guolin Shen
Rok vydání: 2021
Předmět:
Zdroj: Toxicol Res (Camb)
ISSN: 2045-4538
DOI: 10.1093/toxres/tfab014
Popis: Air Potato Yam is widely used in the treatment of many conditions such as cancer, inflammation, and goiter. Diosbulbin B (DIOB) is the primary active component of Air Potato Yam, and it exhibits anti-tumor and anti-inflammatory properties. The main purpose of this study was to determine the mechanism by which DIOB induces lung toxicity, using metabonomics and molecular biology techniques. The results showed that the lung toxicity induced by DIOB may occur because of a DIOB-induced increase in the plasma levels of long-chain free fatty acids and endogenous metabolites related to inflammation. In addition, treatment with DIOB increases the expression of the cyp3a13 enzyme, which leads to enhanced toxicity in a dose-dependent manner. The molecular mechanism underlying toxicity in mouse lung cells is the DIOB-mediated inhibition of fatty acid β-oxidation, partial glycolysis, and the TCA cycle, but DIOB treatment can also compensate for the low Adenosine triphosphate (ATP) supply levels by improving the efficiency of the last step of the glycolysis reaction and by increasing the rate of anaerobic glycolysis. Using metabonomics and other methods, we identified the toxic effects of DIOB on the lung and clarified the underlying molecular mechanism.
Databáze: OpenAIRE