Protective Effects Of "Shaoyao Ruangan Heji" On Chemotherapy-induced Liver Injury

"Shaoyao Ruangan Heji" (SYRG), a liquid pharmaceutical formulation of traditional Chinese medicine, has been used clinically for the prevention and treatment of chemotherapy-induced liver injury in Zhejiang Cancer Hospital (China) for 37 years. However, its underlying therapeutic mechanism is still unclear.ObjectiveTo evaluate the protective effect of SYRG on chemotherapy-induced liver injury, so as to provide evidence for the use of SYRG in treatment of chemotherapy-induced liver injure in clinic.Methods1. SYRG’s free radical scavenging activities were determined by DPPH radical, hydroxyl radical and superoxide anion radical, its antioxidant activities were evaluated by total antioxidative capacity (T-AOC), lipid peroxidation inhibitory activity and metal ions chelating capacity.2. The protective effects of SYRG on 18 commonly used chemotherapeutic agents-induced hepatocellular injury were evaluated in human liver-derived L-02 cells. The cell viability was determined by MTT method.3. In vivo hepatoprotective activity of SYRG was evaluated on cyclophosphamide-induced liver injure in zebrafish by three specific phenotypic endpoints (liver size change, liver transparency and yolk sac retention) and histopathological studies.4. The effects of SYRG on chemotherapeutic agents-induced oxidative stress in hepatocytes were measured through ROS levels by using DCFH-DA.Results1. SYRG had significant DPPH radical, superoxide anion radical and hydroxyl radical scavenging capacity, total antioxidative capacity (T-AOC), lipid peroxidation inhibitory activity and metal ions chelating capacity.2. Pretreatment with SYRG ameliorated fourteen chemotherapeutic agents-induced L-02 cells death, which indicated that SYRG protected against chemotherapeutic agents-induced hepatocellular injury in vitro.3. SYRG reduced cyclophosphamide-induced liver swelling and delay of yolk sac absorption while increased liver transparency, which indicated that SYRG protected against cyclophosphamide-induced hepatocellular injury in zebrafish.4. Pretreatment with SYRG inhibited fourteen chemotherapeutic agents-induced increases of ROS in L-02 cells, which suggested that SYRG reduced chemotherapeutic agents-induced oxidative stress in hepatocytes.Conclusions1. SYRG has protective effects against chemotherapy-induced hepatocellular injury in vitro and in vivo.2. SYRG has significant free radical scavenging and antioxidative capacity, which is correlated directly with its hepatoprotective effect.