Time and dose relationships between schisandrin B- and schisandrae fructus oil-induced hepatotoxicity and the associated elevations in hepatic and serum triglyceride levels in mice

Abstract

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.

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Keywords:

• pharmacodynamics
• hepatomegaly
• alanine aminotransaminase
• affinity
• maximum effect

Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (grant number 31071989).

Disclosure

The authors report no conflicts of interest in this work.