Study On The Mutagenicity And Inhibition Of Atractyloside On Oxidative Phosphorylation

Atractyloside is the main toxic component of Xanthium sibiricum Patr. The fruit of Xanthium sibiricum Patr. is an important Chinese herb. It is widely used in traditional Chinese medicine. Its poisoning because of its misapplication sometimes occurrs in China. The genetic toxicity of atractyloside, however, has few studies, and its toxic mechanism just has a few studies. In this paper, genetic toxicity of atractyloside was studied with Ames test, and the mechanism of its inhibition on oxidative phosphorylation was also studied with MTT test, assaying PTP open rate, activities of respiratory chain complexs and ATPase in mitochondria.The results of Ames test showed that the mutagenic activities of atractyloside at the concentrations within0.8-250μg per plate were not observed in TA97, TA100, and TA102with or without S9. Its mutagenicity on TA98was observed at the concentrations within4-250μg per plate in the presence of S9. The result may caused by toxicity of atractyloside metabolites.The results of assaying mitochondria showed that atractyloside can inhibit the activity of rat hepatic mitochondria. In a certain concentration range, the inhibiton is related to atractyloside concentration.Atractyloside can depress the activities of respiratory chain complex I and IV. This effect has a correlationship with the dose. The activities of respiratory chain complex II and complex III have not evidently changed compared with controls. ROT can inhibit the activity of complex I. but NAC can abate the inhibition. Atractyloside can collaborate with ROT to inhibit complex INa+-K+-ATPase and Ca2+-Mg2+-ATPase had a downward trends compared with controls. The downward trends were relevant to the dose. These two kinds of ATP enzyme activities declined not obviously at20μM of atractyloside. but they declined significantly at100μM.It suggested that atractyloside can inhibit the activites of ATP enzymes, complex I and IV at initating point and end point of respiratory chain separately. The results reduced generating the adenosine triphosphate (ATP).