二苯甲酰甲烷对二甲基甲酰胺致小鼠急性肝损伤的保护作用

Protective effects of dibenzoylmethane against N,N-dimethylformamide-induced acute hepatotoxicity in mice

目的研究二苯甲酰甲烷(DBM)是否可以作为预防和治疗二甲基甲酰胺(DMF)中毒的药物。方法采用DMF(2.5g.kg-1,ip)致小鼠肝损伤模型。预防性给药时分别给小鼠igDBM200,400和800mg.kg-1.d-1,共5d,d4给药30min后,用DMF染毒造模。治疗性给药时在DMF染毒造模30min后分别igDBM100,200和400mg.kg-1.d-1,共2d。染毒48h后,测定血清中谷丙转氨酶(GPT)、谷草转氨酶(GOT)和乳酸脱氢酶(LDH)的活性。留取肝脏组织,常规石蜡包埋切片,HE染色,光镜观察肝脏组织病理变化;制备肝匀浆,测定还原型谷胱甘肽(GSH)和氧化型谷胱甘肽含量。结果与正常组比较,模型组小鼠血清中GPT,GOT和LDH活性明显升高,肝脏组织出现明显的肝细胞变性坏死;预防性和治疗性给予DBM的各剂量组小鼠血清中GPT,GOT和LDH活性与模型组比较显著降低,肝脏组织病理损伤明显减轻,肝匀浆中GSH含量升高。结论DBM对DMF引起的小鼠急性肝损伤具有明显的保护作用。

AIM To evaluate the possibility of dibenzoylmethane （DBM） on prevention and treatment of N, N-dimethylformamide （ DMF ） toxicosis. METHODS Animal experimental models of hepatotoxicity induced by DMF were applied to investigate the preventive and remedial effects respectively. In the preventive experiment, male ICR mice were administered （ig） with DBM 200, 400 and 800 mg· kg^ -1· d^-1, respectively, for 5 d. DMF （2. 5 g· kg^ -1 ） was given （ip） into the mice 30 min after DBM administration experiment, male ICR on d 4. In the remedial mice were given （ip） DMF （2.5 g· kg^ -1 ） , and 30 min later followed by DBM （ig） 100, 200 and 400 mg· kg^ -1·d^-1 for 2 d. The mice serum was prepared and the mice were then euthanized after ip DMF for 48 h. The activities of serum glutamic-pyruvic transaminase （ GPT ） , glutamic-oxaloacetic transaminase （GOT） and lactate dehydrogenase （LDH） were determined, and the liver tissues were collected for histopathological assessment （HE staining ） under light microscope. The levels of glutathione （GSH） and glutathione disulfide in liver homogenate were also quantified. RESULTS After the administration of DMF, the activities of serum GPT, GOT and LDH were significantly increased, and the degeneration and necrosis in liver tissue were observed. In contrast, the activities of these serum enzymes were dominantly decreased in both DBM pretreatment group and posttreatment group compared to that in DMF model group. The histopathological changes in liver were also significantly ameliorated after pretreatment and posttreatment of DBM. Additionally, the content of GSH in liver homogenate was markedly reduced. CONCLUSION DBM had an obvious protective effect against DMF-induced acute hepatotoxicity in mice.