Urinary Excretion of Differently Sized Polyethylene Glycols after Intravenous Administration in Uremic and Control Rats: Effects of Low- and High-Protein Diets

Abstract

The intestine constitutes a barrier towards potentially harmful agents in the intestinal lumen. Different-sized polyethylene glycols (PEGs; range 326–1,162 Da) have been used to study the intestinal permeability properties in ⁵/₆-nephrectomized rats on either a high- (22%) or low-protein (8%) diet. PEGs were administered intravenously, and the urinary recovery was measured. The 24-hour urinary recovery of PEGs was significantly reduced in the uremic groups. The ratios between different sizes of PEGs, indicating a size-selective escape of molecules from blood, were decreased in the uremic groups. The urinary recovery was in general increased in the control group on the high-protein diet compared to the control group on the low-protein diet. The results provide evidence for an increased permeability of larger PEGs (range 634–1,162 Da) in uremic rats and that the protein content of the diet might affect the permeability properties.

Increased Intestinal Permeability to Differently Sized Polyethylene Glycols in Uremic Rats: Effects of Low- and High-Protein Diets

“…The urinary recovery was significantly reduced for all molecular weight species in uremic rats. Furthermore, excretion into the urine was fast, and only negligible amounts of PEGs were detected after 24 h in both uremic or control rats [16].…”

“…Very recently we have studied the urinary recovery of PEGs (range 326-1,162 Da) after intravenous administration in uremic and control rats [16]. The urinary recovery was significantly reduced for all molecular weight species in uremic rats.…”

“…We have very recently investigated the excretion into the urine of differently sized PEGs after intravenous administration in uremic and control rats [16]. First, the investigation showed that recovery of PEGs was reduced over all sizes in the uremic rats in comparison with the control rats.…”

Reduced Intestinal Permeability Measured by Differently Sized Polyethylene Glycols in Acute Uremic Rats

“…This could just reflect the re duced renal function in the uremic group and a prolonged excretion time of PEG in uremia. However, based on the urinary recovery of PEG after intravenous injection in chronic uremic rats, we recently found that the major part of PEG was excreted during the first 6 h, with approximately 76% o f PEG 400 and 82% of PEG 1,000 o f the total amount obtained during 24 hours [18]. Earlier studies have shown that no glomerular exclusion exists o f PEG 400 and 1,000 [19][20][21][22], and that renal clearance o f PEG equals that of creatinine in healthy dogs [22], Furthermore, Chadwick et al…”

“…Recovery ratios between a large and a small test molecule, e.g., a di-and monosaccharide, have been assumed to correct for mucosal surface area, intestinal transit time, length of urine collection time and renal func tion [11,12]. Recovery ratios after intravenous injection in chronic uremic rats were reduced compared to the ratios in normal rats [18], This suggests an increased passage o f larger 1% Magnusson/Magnusson/Sundqvist/ Denneberg PEG from the blood to extravascular compartments, e.g., the intestines, after intravenous administration in chroni cally uremic rats. Furthermore, after oral administration of PEG to chronically uremic rats, the same pattern was seen, a higher urinary recovery and increased recovery ratios of the larger molecules [24], The reduced recovery ratios o f the larger PEG in the present study suggest a decreased absorp tion of the larger molecules in exprimental acute uremia.…”