Studies On The Toxicology Of Phoxim To Rats' Liver

To investigate the effects and mechanism of low concentration phoxim on the liver of rat, in this paper we studied the toxicity and oxidative damage on testes under the exposure of phoxim especially the phoxim of chronic intragastric administration. The microstructure and ultra-microstructure changes of liver were examined and the changes of ChE,antioxidase and production of lipid peroxidation were detected. In addition, we also exposed phoxim to primary cultures of rat hepatocytes. To explore the induction of phoxim on the apoptosis,necrosis of hepatocytes and the effect of ROS on the induction of apoptosis. Apoptotic cells were observed by scanning electron microscope(SEM) and fluorescence microscope, apoptotic rates were determined in flow cytometry (FCM) by Annexin-V,PI double labeling and intra-cellular ROS levels by dihydrorhodamine 123.The research results showed that the activity of ChE excessively decreased in plasma and liver under the chronic phoxim exposure, but no clinical symptom obviously was observed. The activity of ChE in high dose group decreased to 22% and 75% in plasma and liver respectively compared to the control. It can be concluded that appearance of toxicity clinical symptom was not only with the degree of the ChE reduction but mainly with the speed of reduction. The activity of SOD and GSH-Px both decreased in plasma and the content of MDA increased in plasma and liver along with the exposed time extended. Histopathological changes showed fatty degeneration in liver cells of rats. It was concluded that rats exposed to phoxim successively could induce oxidative stress and lesions of structure in the liver.Different dose of phoxim was exposed to primary cultured hepatocytes of rat, It was found that phoxim could damage the hepatocytes directly. The rates of cell apoptosis and death were obviously enhanced and the change was dose-time-dependent. The results showed that intracellular Reactive oxygen species (ROS) levels were advanced with the dose of phoxim. The apoptotic rate was directly correlated with the level of intracellular ROS. It suggested that ROS plays an important role in phoxim inducing apoptosis of hepatocytes.