Amplication Influence of Deoxyschizandrin Towards Adverse Effect of Glioma Therapeutic Drug Irinotecan

Irinotecan is an effective drug for glioma treatment. Irinotecan-induced toxicity strongly limits its clinical utilization, and the glucuronidation of its active metabolite SN-38 is the key inducer for irinotecan-induced toxicity. The present study aims to investigate the influence of deoxyschizandrin towards the toxicity of irinotecan, and the potential mechanism was initially discussed. The pre-treatment of deoxyschizandrin significantly strengthened irinotecan-induced toxicity, indicated by the strengthened damage towards ileum tissue and increased body weight loss. Potential mechanism was investigated through determining the inhibition potential of deoxyschizandrin towards SN-38 glucuronidation. Concentration-dependent inhibition of deoxyschizandrin towards the metabolism of SN-38 was demonstrated. The inhibition type belonged to the competitive inhibition. Through nonlinear fitting using competitive equation, the inhibition kinetic parameter was calculated to be 43.6 mu M. In conclusion, the amplication influence of deoxyschizandrin towards adverse effect of glioma therapeutic drug irinotecan was demonstrated, and the inhibition of deoxyschizandrin towards SN-38 glucuronidation was indicated as the potential mechanism.