Urinary Metabonomic Study on N-Acetylcysteine-Protected Rats with Chronic Renal Failure from Gd-Diethylenetriamine Pentaacetic Acid Administration / 分析化学

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.

Preparation of Novel Biocompatible Macromolecular Magnetic Resonance Imaging Contrast Agent / 分析化学

Poly ( aspartic acid-co-leucine) was synthesized, modified via ethylenediamine, conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and finally chelated with gadoliniumⅢ, yielding PL-A2-DOTA-Gd. The T1-relaxivity (15. 3 mmol-1 ·L·s-1 ) of PL-A2-DOTA-Gd was 2. 6 times than that of Gd-DOTA (5. 8 mmol-1·L·s-1) in D2O. The results of magnetic resonance imaging experiments showed significant enhancement in the rat liver after intravenous administration of PL-A2-DOTA-Gd, which persisted longer than Gd-DOTA. The mean percentage enhancements of liver parenchyma were 65. 1%±5. 2%and 21. 3%±4. 9%, for PL-A2-DOTA-Gd and Gd-DOTA, respectively.