Urinary metabolomics reveals the therapeutic effect of HuangQi Injections in cisplatin-induced nephrotoxic rats

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.

Metabolomic and biochemical characterization of a new model of the transition of acute kidney injury to chronic kidney disease induced by folic acid

“…It was found that some metabolic pathways were shared by some models, such as the citrate cycle, and taurine and hypotaurine metabolism. The same results had been previously reported in experimental models of aristocholic acid and cisplatin (Li et al, 2017; Zhang et al, 2016; Zhao et al, 2015). Simultaneously, glycine, serine and threonine metabolism, together with arginine and proline metabolism, had been reported in adenine and cisplatin model, respectively, (Li et al, 2017; Zhang et al, 2015).…”

Metabolic profiling of metformin treatment for low-level Pb-induced nephrotoxicity in rat urine

“…NMR-based metabolomics is a powerful tool for systematic investigation of potential biomarkers in biofluids 24 . Urine, a waste and filtrate from kidney, is non-invasive and directly reflects renal status 21 , 36 . Therefore, urinary metabolomics coupled with multivariate analysis provide a powerful approach to investigate metformin’s effect on Pb-induced renal injury.…”

“…Non-targeted and targeted strategies are commonly used for metabolomics analyses. The former are suitable for discovering unknown biomarkers, and the latter are used to quantify well-known targets 21 , 22 . One human serum metabolomics study showed that co-exposure to heavy metals disturbs lipid and amino acid metabolism 23 .…”

The Effects of Radix Astragali Water Abstract on Energy Metabolism in Rat Yang‐Deficiency Cold Syndrome Model through PPAR Signaling Pathway

“…RA membranaceus is widely used in clinical treatment of digestive system, respiratory system, cardiovascular diseases, endocrine diseases, and metabolic diseases. It has an enhancing effect on regulating energy metabolism and immune and metabolic functions [ 35 ]. RA also showed advantages including significant treatment effect, no toxic side effects, and less adverse reactions [ 36 – 40 ].…”