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已发表论文

五味子 B-和五味子药材油引起的肝毒性的时间与剂量关系以及小鼠肝脏和血清甘油三酯水平相关的抬高

 

Authors Zhang Y, Pan SY, Zhou SF, Wang XY, Sun N, Zhu PL, Chu ZS, Yu ZL, Ko KM

Published Date September 2014 Volume 2014:8 Pages 1429—1439

DOI http://dx.doi.org/10.2147/DDDT.S67518

Received 10 May 2014, Accepted 10 June 2014, Published 19 September 2014



Background: Schisandrin B (Sch B), a dibenzocyclooctadiene compound, is isolated from schisandrae fructus (SF). This study was conducted to compare the time- and dose-response between Sch B- and SF oil (SFO)-induced changes in hepatic and serum parameters in mice.
Methods: Institute of Cancer Research (ICR) mice were given a single oral dose of Sch B (0.125–2 g/kg) or SFO (0.3–5 g/kg). Serum alanine aminotransferase (ALT) activity, hepatic malondialdehyde, and triglyceride (TG) levels were measured at increasing time intervals within 6–120 hours postdosing.
Results: Serum ALT activity was elevated by 60%, with maximum effect (E max) =45.77 U/L and affinity (K D) =1.25 g/kg at 48–96 hours following Sch B, but not SFO, treatment. Sch B and SFO treatments increased hepatic malondialdehyde level by 70% (E max =2.30 nmol/mg protein and K D =0.41 g/kg) and 22% (E max =1.42 nmol/mg protein and K D =2.56 g/kg) at 72 hours postdosing, respectively. Hepatic index was increased by 16%–60% (E max =11.01, K D =0.68 g/kg) and 8%–32% (E max =9.88, K D =4.47 g/kg) at 12–120 hours and 24–120 hours after the administration of Sch B and SFO, respectively. Hepatic TG level was increased by 40%–158% and 35%–85%, respectively, at 12–96 hours and 6–48 hours after Sch B and SFO treatment, respectively. The values of E max and K D for Sch B/SFO-induced increase in hepatic TG were estimated to be 22.94/15.02 µmol/g and 0.78/3.03 g/kg, respectively. Both Sch B and SFO increased serum TG (up to 427% and 123%, respectively), with the values of E max =5.50/4.60 mmol/L and K D =0.43/2.84 g/kg, respectively.
Conclusion: The findings indicated that Sch B/SFO-induced increases in serum/hepatic parameters occurred in a time-dependent manner, with the time of onset being serum TG level < hepatic TG level < hepatic index < serum ALT activity. However, the time of recovery of these parameters to normal values varied as follow: serum TG level < hepatic TG level and liver injury < hepatic index. The E max and affinity of Sch B on tissue/enzyme/receptor were larger than those of SFO.
Keywords: pharmacodynamics, hepatomegaly, alanine aminotransaminase, affinity, maximum effect



视频地址：Schisandrin B/schisandrae fructus and hepatotoxicity


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