当前位置： SCI文献检索 > TOXICOLOGY AND APPLIED PHARMACOLOGY期刊下所有文献 > Untargeted LC-MS-based metabonomics revealed that aristolochic acid I induces testicular toxicity by inhibiting amino acids metabolism, glucose metabolism, β-oxidation of fatty acids and the TCA cycle in male mice.

Untargeted LC-MS-based metabonomics revealed that aristolochic acid I induces testicular toxicity by inhibiting amino acids metabolism, glucose metabolism, β-oxidation of fatty acids and the TCA cycle in male mice.

Abstract：

:As the main toxic component of aristolochic acid, aristolochic acid I (AAI) is primarily found in Aristolochiaceae plants such as Aristolochia, Aristolochia fangchi and Caulis aristolochiae manshuriensis. AAI has been proven to be carcinogenic, mutagenic and nephrotoxic. Although the role of AAI in testicular toxicity has been reported, its mechanism of action is unknown. Using metabonomics and molecular biology techniques, we tried to identify the differential endogenous metabolites of AAI that may affect the changes in testicular function in mice, map the network of metabolic pathways, and systematically reveal the molecular mechanism of AAI-induced testicular toxicity. We found that AAI inhibited amino acid metabolism in mouse testicular cells, impeded the uptake and oxidative decomposition of fatty acids, prevented normal glucose uptake by testicular cells, which inhibited glycolysis and gluconeogenesis, affected the mitochondrial tricarboxylic acid (TCA) cycle, which impaired the ATP energy supply, decreased the number of spermatogenic cells and sperm in the testes, induced changes in the mitochondrial state of spermatogonial cells, and ultimately led to physiological and pathological changes in the testes. AAI also regulated the testicular physiological activity by regulating the androgen receptor and hormone levels. This study used metabonomics and other methods to elucidate the mechanism of AAI-induced testicular toxicity from a new angle.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Cui Y,Han J,Ren J,Chen H,Xu B,Song N,Li H,Liang A,Shen G

doi

10.1016/j.taap.2019.04.014

subject

Has Abstract

pub_date

2019-06-15 00:00:00

pages

26-38

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(19)30146-2

journal_volume

373

pub_type

杂志文章

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