Schisandra chinensis extract decreases chloroacetaldehyde production in rats and attenuates cyclophosphamide toxicity in liver, kidney and brain

Abstract

Ethnopharmacological relevanceSchisandra chinensis (Turcz.) Baill (S. chinensis) has been used for thousands years in China, and is usually applied in treatment of urinary tract disorders and liver injury. S. chinensis extract (SCE) has board protective effects on liver, kidney and nervous system. Schisandra lignans are generally considered as the bioactive components of SCE. Aim of the studyTo investigate the pharmacokinetic herb-drug interactions (HDIs) between SCE and cyclophosphamide (CTX). To evaluate the protective effects of SCE against CTX induced damage in rat liver, kidney and brain. Materials and methodsThe pharmacokinetic HDIs between SCE and CTX were investigated by determining plasma concentrations of CTX and three metabolites, namely 4-ketocyclophosphamide (4-Keto), 2-dechloroethylcyclophosphamide (DCCTX) and carboxyphosphamide (CPM) using a previously developed UPLC-MS/MS method. To evaluate the protective effects of SCE pretreatment, toxicity and oxidation stress assessments along with histology investigations were carried out in rat liver, kidney and brain. ResultsThe equimolar produced metabolite DCCTX was chosen to reflect chloroacetaldehyde (CAA, a toxic metabolite of CTX) production in rats. Single-dose pretreatment of SCE significantly reduced CAA production and decreased the Cmax and AUC0–24h of DCCTX by 69% and 49% respectively (P < 0.05). After pretreated with SCE for 7 consecutive days, the Cmax and AUC0–24h of DCCTX were still decreased (−25% and −37%, P < 0.05) when compared with CTX alone group. Parallel toxicity and oxidation stress investigations showed that single-dose SCE pretreatment significantly decreased plasma BUN and Cr levels (−12% and −46%, respectively) and reduced liver AST activity (−32%). Moreover, SCE pretreatment potently increased the brain GSH content by 7.8-fold, and reduced MDA levels in rat liver, kidney and brain by 39%, 28% and 31%, respectively (compared with CTX alone group). The protective effects of SCE were also supported by histological observations. ConclusionOur experiment results suggest that S. chinensis may find use as a complementary medicine in CTX treatment.