Intestinal absorption and biliary secretion of cholesterol in rats with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) results in hypercholesterolemia which is attributed to increased production and decreased removal of cholesterol-rich lipoproteins. Adjustments in intestinal absorption are reportedly involved in cholesterol homeostasis. We, therefore, studied the intestinal absorption and biliary excretion of cholesterol in NS. METHODS: We studied intestinal absorption (by in vivo perfusion and in vitro everted sac incubation techniques) and biliary secretion (by common bile duct cannulation) of cholesterol in rats with puromycin-induced NS. The results were compared with those obtained from pair-fed control (PF) animals, those given free access to food (NL) or those fed a hypercholerolemic diet (H-chol group). Micellar solutions of Krebs' phosphate buffer containing trace amounts of [14C]inulin and [3H]cholesterol, as well as different concentrations of unlabeled cholesterol, were used for absorption studies. RESULTS: The NS and H-chol groups showed severe and comparable hypercholesterolemia. No significant difference was found in the rate of biliary cholesterol secretion among the study groups. Likewise, the rates of in vivo and in vitro cholesterol absorptions in the NS and H-chol groups were comparable with one another and similar to those found in the NL and PF groups. The rate of in vitro cholesterol absorption was directly proportional to its concentration in the incubation media at low concentrations. However, the absorption rate showed a pattern consistent with saturable transport at high cholesterol concentrations in all groups. CONCLUSIONS: We conclude that intestinal absorption and biliary secretion of cholesterol are not appreciably influenced by either nephrotic or diet-induced hypercholesterolemia in rats. The data further suggest that cholesterol absorption may be a saturable process.

Functional, biochemical, and histopathologic consequences of high-dose interleukin-2 administration in rats.

A variety of side effects have been reported with the use of interleukin-2 alone or in combination with lymphokine-activated killer cells in patients with disseminated neoplasms. The present study was undertaken to determine the effects of high-dose interleukin-2 administration in normal rats. Sprague-Dawley rats were treated with intravenous recombinant interleukin-2 (900,000 IU/kg/day) for 9 consecutive days. Animals were placed in individual metabolic cages, and arterial blood pressure, food intake, body weight, and urine output were monitored. On day 10, animals were killed by exsanguination, various tissues were harvested, and a variety of hematologic and chemical assays were performed. The results were compared with those of placebo-injected normal control and pair-fed groups. The interleukin-2-treated group exhibited anorexia, weight loss, hypotension, anemia, leukocytosis, lymphocytosis, eosinophilia, hypercalcemia, azotemia, and a marked urinary concentration defect. Histologic examination of various tissues revealed widespread infiltration with mono-nuclear cells and eosinophils in most organs, especially in the lungs and liver of interleukin-2-treated animals. Other abnormalities included severe panlobular hepatitis, hepatocellular necrosis, and thymic involution. Renal involvement was mild and consisted of focal interstitial infiltration by mononuclear cells. According to these observations, administration of high-dose interleukin-2 in normal rats results in a score of significant functional, biochemical, and histologic abnormalities.

Vitamin D absorption, plasma concentration and urinary excretion of 25-hydroxyvitamin D in nephrotic syndrome.

Nephrotic syndrome (NS) is commonly associated with vitamin D deficiency. Urinary losses of the protein-bound intermediary metabolite of this vitamin is thought to contribute to the deficiency state. The role of possible changes, if any, of vitamin D absorption has not been investigated previously in NS. We determined intestinal absorption of vitamin D3 as well as plasma concentration and urinary excretion of 25-hydroxyvitamin D3 in rats with puromycin aminonucleoside-induced NS. In vivo recirculating perfusion technique was employed at 100 and 600 nM perfusate concentrations. The results were compared with those obtained in animals receiving placebo injections provided with either free access to food (normal controls) or those pair-fed with their NS counterparts (pair-fed group). The NS group showed heavy proteinuria and hypoalbuminemia. In addition, the NS group exhibited marked urinary losses and significantly reduced plasma concentration of 25-hydroxyvitamin D. The rate of vitamin D3 absorption (given as nmol/100 cm/min) at 100 nM perfusate concentration in the NS group (0.161 +/- 0.029) was not significantly different from those obtained in the pair-fed group (0.202 +/- 0.058) and the normal control group (0.143 +/- 0.053). Likewise, no significant difference was found in the rats of vitamin D absorption at 600 nM concentration among the NS (1.073 +/- 0.383), pair-fed (0.955 +/- 0.229), and normal control (0.756 +/- 0.314) groups. Accordingly, intestinal absorption of vitamin D appears to be unaffected by the presence of experimental NS and as such the associated vitamin D deficiency can be managed by enteral supplementation.

Glomerulopressin activity in carbon tetrachloride-induced cirrhosis in male rats.

The activity of glomerulopressin, a putative renal vasoregulatory hormone that is synthesized in the liver, was assayed in male rats with carbon tetrachloride-induced cirrhosis and the results were compared to glomerulopressin activity in normal-control and pair-fed animals. Glomerulopressin activity in blood samples collected from the hepatic vein of the cirrhotic group was significantly lower than the activity in the normal-control and pair-fed groups. Glomerulopressin activity in the normal-control and the pair-fed groups were not significantly different. The data support the concept that glomerulopressin deficiency in liver disease, such as cirrhosis, may play a role in the genesis of the functional renal failure associated with liver disease.

Glucose intolerance in renal failure: role of endogenous opioids.

Plasma concentrations of glucose, insulin, and beta-endorphin/beta-lipotropin were measured in male Sprague-Dawley rats with experimental renal failure after intravenous glucose challenge in the presence and absence of opioid blockade with intravenously administered naloxone. The results were compared with those obtained in sham-operated normal control and pair-fed groups of animals. Baseline glucose concentrations were similar in the three groups of animals. Plasma baseline insulin concentrations were significantly lower in the rats with renal failure and the pair-fed animals compared with the normal controls. After glucose challenge the renal failure group demonstrated glucose intolerance, which was not improved after naloxone treatment given 15 minutes before glucose challenge. Peak insulin levels after glucose challenge in the renal failure and pair-fed groups increased significantly after naloxone administration. Interestingly, circulating concentrations of plasma beta-endorphin/beta-lipotropin were not significantly different in the three groups of animals when measured either in the baseline state or after glucose challenge. The data indicate that the carbohydrate intolerance in experimental renal failure may be partly due to an increase in pancreatic islet opioidergic tone, because an improvement in insulin secretion was demonstrated in the absence of any change in circulating beta-endorphin/beta-lipotropin concentrations after naloxone. The failure to demonstrate any improvement in glucose disposal after naloxone, despite the augmented secretion of insulin after naloxone in the animals with renal failure, points to peripheral resistance to the effects of insulin that is not influenced by opioid blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Intestinal morphometry and bile acid-induced mucosal injury in chronic experimental renal failure.

To examine whether the intestinal mucosa in uremia is more prone to injury, we studied acute intestinal mucosal injury in rats with experimental chronic renal failure (RF) and sham-operated and starved control animals. Intestinal injury was produced by perfusing intestinal segments in vivo with 5 mmol/L chenodeoxycholic acid. Histologic specimens were then taken from the proximal and distal perfused and unperfused intestinal segments. Quantitative morphometry was done with computerized image analysis, and samples of the unperfused intestine were assayed for protein and DNA content. Chronic RF did not significantly affect the functional or morphologic injury caused by chenodeoxycholic acid. However, it was noted that RF rats had consistently taller villi and deeper crypts in all the samples studied. The protein content and the ratio of DNA to protein was similar among the three groups. The mechanism of the increase in villus height and crypt depth in the RF rats was not related to increases in tissue water content or to alterations in protein or DNA content, and the mechanism thus remains unexplained. This study clearly demonstrates, however, that the intestinal mucosa of rats with chronic renal insufficiency is not more susceptible to mucosal injury by bile acids than is the mucosa of appropriate control animals.

Intestinal absorption of vitamin E in experimental renal failure.

We studied intestinal absorption of vitamin E in rats with experimental renal failure (RF) and in sham-operated normal and pair-fed controls using in vivo perfusion and in vitro everted sacs. The in vivo absorption rates per unit of intestine length were significantly reduced in RF and pair-fed groups. Expression of data per unit of intestine weight gave normal values in the pair-fed but depressed values in the RF animals. Vitamin E uptake in vitro was significantly increased in RF animals, suggesting enhanced permeability. We conclude: (i) vitamin E absorption in vivo is impaired in experimental RF; (ii) this is in part due to reduced nutrient intake; and (iii) disparity between in vivo and in vitro results suggests the presence of some inhibitory influence(s) in intact animals with RF.