Experimental Study Of Amphetamine To Rat Hepatotoxicity

PURPOSEThe most researchs about amphetamine (AP) now are mainly focused on its reaction aboutcentral nervous system and the relative products, however, the toxicity of the drug and itsmetabolic rules inside body organs are real few.Our experiment was to study the toxicity role of AP to rat liver. We built up model of ratsinjected by AP, in order to observe the morphological changes of liver and the expression of fattyacid synthase under the conditions of different doses and different times.METHODSSD rats were randomly divided into control and model groups. The control group has 5 ratsand was treated intramuscularly with normal saline every day. The model group was divided intolow(0.5mg/kg), medium(2.5mg/kg) and high(5mg/kg) dose groups, each group with 20 rats. APwas injected intramuscularly in the model group every day. At 14d, 28d and 42d, rats in everygroup were sacrificed (n=5 each time). The morphological changes of liver were analyzed by HEstained, and change of the number of fatty acid synthase(FAS)-positive cells was examined byimmunohistochemical method, and then change of the content of the FAS were measured withWestern Blot.RESULTSThe hepatic sinus were narrowing or disappeared with histological disturbance. Hepatocyteswere swollen and lipid droplets were founded in the cytoplasma. Steatosis was locally ordiffused in the hepatic tissue. In severe cases, hepatocytes were ballooning with the nuclearpyknosis. The hepatotoxicity was dependent on the drug dose and adminstration time.The FAS positive cells were stained with brown yellow in the cytoplasma byimmunohistochemical method. The number were decreased with the increase of the drug doseand adminstration time.The content of FAS was demonstrated a decrease with the increase of dose and time byWestern Blot. CONCLUSIONSAP has an obvious toxical action on liver. The hepatotoxic action mainly showed the cellularsteatosis and edema. At the mean time, the number of FAS-positive cells and the content of FASwere decreased with the increase of the drug dose and administration time.