Schalkwijk C G, Posthuma N, ten Brink H J, ter Wee P M, Teerlink T
Department of Clinical Chemistry, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Perit Dial Int. 1999 Jul-Aug;19(4):325-33.
To study the presence of 1,2-dicarbonyl compounds in peritoneal dialysis (PD) fluids, their concentration in effluents with increasing dwell time, and their role in the formation of advanced glycation end-products (AGEs).
Dicarbonyl compounds in heat- and filter-sterilized PD fluids were quantified by reverse-phase high performance liquid chromatography (HPLC) after derivatization to dimethoxyquinoxaline derivatives. Kinetics of the in vitro formation of AGEs upon incubation of 1,2-dicarbonyl compounds or PD fluids with albumin, with or without aminoguanidine, were measured by AGE fluorescence (excitation/emission wavelengths of 350 nm/430 nm).
AGEs and dicarbonyl compounds were measured in effluents collected from standardized 4-hour dwells from 8 continuous cycling peritoneal dialysis patients.
In PD fluids, 3-deoxyglucosone (3-DG) has been identified as the major dicarbonyl compound formed during the process of heat sterilization. The process also formed glyoxal (GO) and methylglyoxal (MGO), with the amount of 3-DG being approximately 25-60 times higher than GO and MGO. When incubated with albumin, the identified 1,2-dicarbonyl compounds rapidly formed AGEs. The formation of AGEs was more pronounced in conventional heat-sterilized PD fluids compared with filter-sterilized PD fluids, and was completely inhibited by aminoguanidine. In effluents, the concentration of MGO, GO, and 3-DG decreased with increasing dwell time, with a concomitant increase in AGE fluorescence.
The dicarbonyl compounds 3-DG, MGO, and GO are potent promoters of AGE formation. The presence of these and possibly other dicarbonyl compounds formed during heat sterilization of glucose-based PD fluids is, to a large extent, responsible for the in vitroAGE formation by these fluids, as evidenced by the speed of AGE formation in PD fluids and the complete inhibition by aminoguanidine. Because 3-DG, MGO, and GO are rapidly cleared from PD fluids during dialysis, these compounds may contribute to the in vivo AGE formation in PD patients.
研究腹膜透析(PD)液中1,2 - 二羰基化合物的存在情况、其在随着驻留时间增加的流出液中的浓度,以及它们在晚期糖基化终产物(AGEs)形成中的作用。
经过加热和过滤灭菌的PD液中的二羰基化合物在衍生化为二甲氧基喹喔啉衍生物后,通过反相高效液相色谱(HPLC)进行定量。通过AGE荧光(激发/发射波长为350 nm/430 nm)测量1,2 - 二羰基化合物或PD液与白蛋白一起孵育时(有无氨基胍)体外AGE形成的动力学。
从8名持续循环腹膜透析患者的标准化4小时驻留中收集的流出液中测量AGEs和二羰基化合物。
在PD液中,3 - 脱氧葡萄糖酮(3 - DG)已被鉴定为热灭菌过程中形成的主要二羰基化合物。该过程还形成了乙二醛(GO)和甲基乙二醛(MGO),3 - DG的量比GO和MGO高约25 - 60倍。与白蛋白一起孵育时,鉴定出的1,2 - 二羰基化合物迅速形成AGEs。与过滤灭菌的PD液相比,传统加热灭菌的PD液中AGEs的形成更明显,并且被氨基胍完全抑制。在流出液中,MGO、GO和3 - DG的浓度随着驻留时间的增加而降低,同时AGE荧光增加。
二羰基化合物3 - DG、MGO和GO是AGE形成的有效促进剂。基于葡萄糖的PD液热灭菌过程中形成的这些以及可能的其他二羰基化合物的存在,在很大程度上导致这些液体在体外形成AGEs,PD液中AGE形成的速度以及氨基胍的完全抑制证明了这一点。由于3 - DG、MGO和GO在透析过程中会迅速从PD液中清除,这些化合物可能有助于PD患者体内AGE的形成。