RESUMO
N-Acetylcysteine (NAC) protects rats administrated with gadolinium-based contrast agents from renal injury, however, the underlying mechanisms remain unclear.A 1H NMR-based metabolomics approach coupled with OPLS-DA (orthogonal projection to latent structure with discriminant analysis) was used to analyze the effect of NAC on urinary metabolic changes for Chronic Renal Failure Rats administrated with Gd-DTPA (Gd-Diethylenetriamine pentaacetic acid).Combined with univariate analysis of integral area, the significantly changed metabolites were selected to screen out the potential metabolic disturbances that induced by Gd-DTPA and NAC.These researches may attribute to study of the protective effect of NAC from renal failure induced by gadolinium-based contrast agents.The disturbance of energy metabolism, urea cycle and kynurenine metabolism were observed from the CRF group.Gd-DTPA caused the reduction of urinary choline, TMAO, o-HPA, p-HPA, hippurate, glycine, nicotinate and taurine accompanied with the elevation of allantoin.Metabonomic recovery in the NAC group was observed, which implied that NAC protects rats with chronic renal failure from Gd-DTPA induced disturbances of gut microbiota metabolism, liver mitochondria metabolism and kynurenine metabolism.The replenishment of glutathione in cells and the recovery of urea cycle that caused by NAC may protect rats from oxidative damage and renal injury.
RESUMO
Wistar rats were intragastrically administered with different doses (2, 5 and 10 g / kg body weight) of haematitum. 1H NMR-based metabonomic analysis coupled with multivariate statistical analysis (principal component analysis and partial least squares-discriminant analysis) was used to analyze the metabolic profiles of the urine samples collected from the treated rats. Univariate analysis on the 1H NMR spectra of urine (1 d before administration, 1-5 d post administration) was used to screen out the potential features of haematitum. Significant treatment related changes were observed for the levels of citrate, tuarine, creatinine,α-ketoglutarate, succinate and dimethylglycine, which could be used as potential features of haematitum. A trend of recovery in connection with dose levels was observed overtime. Such biochemical changes indicated that haematitum treatment at the dose of 2, 5 and 10 g / kg body weight affected the Krebs cycle and glucose metabolism, energy metabolism, choline metabolism and dimethylglycine metabolism in rats. These changes may attribute to the disturbances of hepatic function in 10 g / kg body weight group.
