Abstract
The side effects of cisplatin (CDDP), notably nephrotoxicity, greatly limited its use in clinical chemotherapy. HuangQi Injections (HI), a commonly used preparation of the well-known Chinese herbal medicine Astragali radix, appeared to be promising treatment for nephrotoxicity without compromising the anti-tumor activity of CDDP. In this study, the urinary metabolomics approach using liquid chromatography time of flight mass spectrometry (LC-TOF/MS) was developed to assess the toxicity-attenuation effects and corresponding mechanisms of HI on CDDP-exposed rats. As a result, successive administration of HI significantly recovered the decline of body weight and downregulated the abnormal increase of serum creatinine and urea. HI partly restored the CDDP-induced alteration of metabolic profiling back into normal condition. Totally 43 toxicity-attenuation potential biomarkers were screened and tentatively identified, which were involved in important metabolic pathways such as amino acid metabolism, TCA cycle, fatty acid metabolism, vitamin B6 metabolism and purine metabolism. The results clearly revealed that HI could alleviate CDDP-induced nephrotoxicity and improve the disturbed metabolic balance induced by repeated CDDP exposure. The present study provided reliable evidence for the protective effect of HI on CDDP-induced toxicity with the multi-target pharmacological characteristics.
Highlights
IntroductionAs a holistic approach reflecting comprehensive changes of endogenous metabolites in bio-fluids and tissues, metabolomics has been widely applied to the study of the pathogenesis of nephrotoxicity or kidney diseases and discover new biomarkers as well as effect of drug intervention and therapeutic mechanism[1,2,3,4]
Nephrotoxicity or renal toxicity has grown rapidly in the past ten years
It can be seen that remarkable decline of body weights (BWs) in Group CDDP were observed on day 11 and 20, while successive administration of HuangQi Injections (HI) for 16 days could significantly recover this decline
Summary
As a holistic approach reflecting comprehensive changes of endogenous metabolites in bio-fluids and tissues, metabolomics has been widely applied to the study of the pathogenesis of nephrotoxicity or kidney diseases and discover new biomarkers as well as effect of drug intervention and therapeutic mechanism[1,2,3,4]. The renoprotective effects of the layer of Poria cocos were systematically studied by using metabolomics approach[15,16,17]. These studies based on metabolomics technique demonstrated TCMs had a beneficial effect on treatment of kidney disease and highlighted the biochemical action mechanism of anti-tubulointerstitial fibrosis. The objective of the present study is to investigate the toxicity-attenuation effect of the commonly used RA preparation HuangQi Injections (HI) in the CDDP-exposed rats using LC-TOF/ MS-based urinary metabolomics method
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