The Mitochondrial Damage Mechanism Of Hepatotoxicity On Mice Induced By Beryllium Sulfate

Objective：To observe beryllium sulfate (BeSO4·4H2O)-induced hepatotoxicity on mice viaanimal experiment, and explore possible mechanism about mitochondrial damage ofhepatotoxicity on mice induced by beryllium sulfate.Methods：1.30six-week-old healthy male Kunming (KM) mice were randomly dividedinto3groups of10each. Control group was designated sterile saline solution byintraperitoneal injection (0.1ml/10g body weight), treatment groups including lowdose group and high dose group were administered with solution of beryllium sulfateat following doses:1mg/kg b.w. and2mg/kg b.w. by intraperitoneal injectionrespectively, every other day for two weeks. The general instance of mice wereobserved.2. All mice were sacrificed by neck breaking method, serum alanine aminotransferase (ALT) and serum aspartate amino transferase (AST) activity were detectedby automated biochemistry analyzer; Integral liver were harvested, in order to accountthe level of liver organ coefficient; Hepatic histopathological change were observedunder light microscope by hematoxylin and eosin (HE) stainning.3. The mitochondria were isolated by differential centrifugation from liverhomogenate. Mitochondrial membrane potential (Δψm) were monitored byspectrofluorimeter with fluorescence dye Rhodamine123（Rh123）and the content ofROS were detected by spectrofluorimeter with fluorescence dye DCFH-DA;Mitochondrial permeability transition pore（PTP）opening extent were assessedmitochondria swelling via spectrophotometrically in absorbance at520nm (A520);The content of mitochondrial cytochrome c (Cytc), mitochondrial malondialdehyde (MDA) and the activity of mitochondrial glutathione peroxidase (GSH-Px) weremeasured by spectrophotography; The activity of mitochondrial superoxide dismutase(SOD) were detected using ultraviolet spectrophotometer.Results：1. The signs of mice in control group and treatment groups were not evidentdifference. Compared with the control group, the weight in treatment groups were notsignificant changed (P>0.05).2. The level of liver organ coefficient, serum ALT and AST activity in treatmentgroups were significantly higher than those in the control group (P<0.05); The liverhistopathology of control group showed hepatic cell morphosis normal; It was seenhepatocytes swollen and focal necrosis in low dose group; A strong vacuolardegeneration of cytoplasm and denaturation even necrosis were the main pathologicchanges in high dose group.3. Compared with the control group, mitochondrial Δψm decreased in treatmentgroups (P<0.05); The activity of mitochondrial SOD and GSH-Px in treatment groupswere significantly lower than those in the control group (P<0.05)；The treatmentgroups showing evident mitochondrial PTP opened (P<0.05); The content ofmitochondrial Cytc, mitochondrial ROS and mitochondrial MDA in treatment groupswere more higher than those in the control group (P<0.05).Conclusions：1. Beryllium sulfate can induce dysfunction of mice liver and the hepatic tissuespathologic changed obviously, beryllium sulfate can induce obvious hepatotoxicity onmice.2. The hepatic mitochondrial Δψm, the activity of mitochondrial SOD andGSH-Px were decreased by beryllium sulfate; The mitochondrial PTP opened, thecontent of mitochondrial Cytc, ROS and MDA were increased by beryllium sulfate.3. Mitochondrial dysfunction and mitochondrial oxidative damage maybe mainreason of beryllium sulfate-induced hepatotoxicity on mice, the mitochondria maybeappear to be a target point of hepatotoxicity when suffered toxicant from berylliumsulfate.