SummaryIn vivo jejunal transport of amino acids, monosaccharides, sodium, and electrolytes were studied in rats made nephrotic with puromycin Pmioonucleoside (PAN) and in pair-fed controls. Studies were performed 14 days after a single intravenous dose of PAN when rats were no longer edematous, but were stlll hypoproteinemic. There was decreased absorption of glucose, 31)-methyl glucose, glycine, phenylalanine, histidine, water, and sodium in the nephrotic animals but transport of fructose, lysine and potassium was similar in the nephrotic and control animals. Enzyme kinetic studies for glucose transport showed a mixed type of inhibition affecting both Vm and Km. The jejunal mucosa of nephrotic and control rats had similar ATP content and enzyme activity for Iactase, sucrase, maltase and (Na-K)-ATPase and the ratios of RNA to DNA were similar in the nephrotic and control rats. No abnormality of the jejunum was detected by tight or electron microscopy. The data suggest that the impairment of absorption is a result of decreased activity of jejunal membrane carrier mechanisms. The altered transport may be secondary to effects related to the metabolic consequences of nephrotic syndrome and does not appear to be related to acute purine aminonucleoside toxicity, edema or malnutrition.
Abbreviations
BUN, blood urea nitrogen PAN, puromycin aminonucleoside PEG, polyethylene glycolThe nephrotic syndrome, characterized by proteinuria, hypoproteinemia, and edema is essentially a protein depletion state (4). An experimental nephrotic model has been available since 1955 when Frenk et al. (9) reported that an aminonucleoside of puromycin, a derivative of the antibiotic puromycin, was capable of regularly producing nephrotic syndrome in rats; nevertheless, few investigations have been carried out on intestinal absorption of nutrients in the nephrotic syndrome. In order to help clarify what effect the ne~hrotic state and its associated metabolic changes might have o i intestinal absorption, we evaluated jejunal transport of nutrients in nephrotic rats 14 days after intravenous treatment with purine aminonucleoside. The results were compared to those of pair-fed controls and indicated a generalized decrease in jejunal absorption in the nephrotic rats.
MATERIALS AND METHODSSeventy-four adult male Wistar rats (37), weighing 180-200 g, were randomized into experimental and control groups. The nephrotic syndrome was induced in each animal in the experimental group by intravenous injection of 7.5 mg/100 g body weight of PAN as a 15 mg/ml solution. The controls were given an equal volume of saline. Control rats were pair-fed by being given the same amount of Purina Lab Chow (38) as their nephrotic wunterparts had taken the preceding day. Water intake was allowed ad libitum. Baseline studies were conducted, measuring the daily urine output and the amount of qualitative proteinuria. Intake and weight gain were recorded. Thirteen days after the administration of PAN, 24-h urine protein excretion was quantitated and blood was drawn for se...