Intestinal Calcium Absorption In Rats Research Articles

Intestinal Calcium Absorption in Rats Is Stimulated by Dietary Lactulose and Other Resistant Sugars

Lactulose is a disaccharide analogue of lactose that is resistant to metabolism in the small intestine but not in the large intestine. The effects of lactulose and other sugars on intestinal Ca absorption were determined from the decrease in the 47Ca:47 Sc ratio between diet and feces after feeding male rats diets containing these sugars during a single night. Dietary lactulose was more potent than lactose in stimulating Ca absorption and was effective between 5 and 38 wk of age. The component sugars of lactulose, galactose and fructose, did not influence Ca absorption when provided together at concentrations equimolar to that of lactulose. The stimulation of Ca absorption by dietary lactulose increased as dietary Ca concentration was raised and was not influenced by prior injections of calcitriol. Lactulose must be present in the same meal as Ca to stimulate Ca absorption, but this stimulation was lost if the rats were fed lactulose continuously for 2 or 7 d prior to the test diet. Other sugars thought to be poorly absorbed in the small intestine (xylitol, lactobionate, arabinose, raffinose, pyroglutamate, sorbitol, gluconate and raftilose) stimulated Ca absorption to an identical extent as lactulose. Cecectomy did not influence the enhancement of Ca absorption by lactulose. These results indicate that sugars resistant to metabolism and absorption in the small intestine but not the large intestine stimulate Ca absorption in the small intestine.

The Effect of Dietary Protein on Intestinal Calcium Absorption in Rats

Increasing dietary protein intake in humans acutely increases urinary calcium. Isotopic absorption studies have indicated that, at least in the short term, this is primarily due to increased intestinal Ca absorption. To explore the mechanisms underlying dietary protein's effect on intestinal Ca absorption, female Sprague Dawley rats were fed a control (20%), low (5%), or high (40%) protein diet for 7 d, and Ca balance was measured during d 4-7. On d 7, duodenal mucosa was harvested and brush border membrane vesicles (BBMVs) were prepared to evaluate Ca uptake. By d 7, urinary calcium was more than 2-fold higher in the 40% protein group compared with control (4.2 mg/d vs. 1.7 mg/d; P < 0.05). Rats consuming the 40% protein diet both absorbed and retained more Ca compared with the 5% protein group (absorption: 48.5% vs. 34.1% and retention: 45.8% vs. 33.7%, respectively; P < 0.01). Ca uptake was increased in BBMVs prepared from rats consuming the high-protein diet. Maximum velocity (V(max)) was higher in the BBMVs prepared from the high-protein group compared with those from the low-protein group (90 vs. 36 nmol Ca/mg protein x min, P < 0.001; 95% CI: 46-2486 and 14-55, respectively). The Michaelis Menten constant (K(m)) was unchanged (2.2 mm vs. 1.8 mm, respectively; P = 0.19). We conclude that in rats, as in humans, acute increases in protein intake result in hypercalciuria due to augmented intestinal Ca absorption. BBMV Ca uptake studies suggest that higher protein intake improves Ca absorption, at least in part, by increasing transcellular Ca uptake.

Comparative Effects of Vitamin K and Vitamin D Supplementation on Calcium Balance in Young Rats Fed Normal or Low Calcium Diets

We examined the effect of vitamin K and vitamin D supplementation on calcium balance in young rats fed a normal or low calcium diet. Eighty female Sprague-Dawley rats, 6 wk of age, were randomized by the stratified weight method into eight groups with 10 rats in each group: 0.5% (normal) or 0.1% (low) calcium diet, 0.5% or 0.1% calcium diet+vitamin K (vitamin K2, menatetrenone, 30 mg/100 g, food intake), 0.5% or 0.1% calcium diet+vitamin D (25 microg/100 g, food intake), and 0.5% or 0.1% calcium diet+vitamin K+vitamin D. The duration of the study was 10 wk. Vitamin K supplementation promoted the reduction in urinary calcium excretion and retarded the abnormal elevation of serum PTH level in rats fed a low calcium diet, and stimulated intestinal calcium absorption in rats fed a normal calcium diet. Vitamin D supplementation stimulated intestinal calcium absorption with prevention of the abnormal elevation of serum PTH levels and prevented hypocalcemia in rats fed a low calcium diet, and stimulated intestinal calcium absorption in rats fed a normal calcium diet. The stimulation of intestinal calcium absorption was associated with increased serum 1,25-dihydroxyvitamin D levels. An additive effect of vitamin K and vitamin D on intestinal calcium absorption was found only in rats fed a normal calcium diet. This study shows the differential effects of vitamin K and vitamin D supplementation on calcium balance in young rats fed a normal or low calcium diet.

Diet composition and age determine the effects of inulin–type fructans on intestinal calcium absorption in rat

Although several studies in animals and humans have established that inulintype fructans (inulin, oligofructose, fructooligosaccharides) enhance intestinal Ca absorption, there are also reports that failed to demonstrate any effects of added fructans on Ca absorption. We investigated in a rat model what variables determine inulin actions on mineral absorption with special focus on the basic diet. To determine apparent intestinal mineral absorption, whole body retention and mineral accumulation in bone, we performed feeding experiments with a balance technique by which mineral intake, faecal and urinary output are determined. In a first study we compared the effects of an inulin oligofructose mixture (0 and 10%,respectively) when added either to a standard diet or a semi-synthetic diet. Rats fed the semi-synthetic diet were younger (adolescent) than rats on standard diet (young adult). We observed that the apparent Ca absorption ratio was significantly increased by inulin and oligofructose only when provided in the semisynthetic diet and not in the standard diet that intrinsically already contained some fructans from wheat. In our second study with a semi-synthetic diet fed to growing (adolescent) rats, inulin and oligofructose increased not only Ca but also Mg and Zn absorption, whole body mineral retention and femur mineral content. Inulin-type fructans at dietary levels of 10 % (w/w) do increase mineral absorption, retention and accumulation in bone in the case of Ca, Mg and Zn, but only when the basic diet for the control group contains no intrinsic fructans and when the mineral demand is particularly high as during growth.

Influence of various proteins on intestinal calcium absorption in rats

Influence of various proteins on intestinal calcium absorption in rats

Further studies on acute effect of prolactin on intestinal calcium absorption in rat

The present investigation aimed to (1) reconfirm the acute effect of prolactin on intestinal calcium absorption in the rat, (2) evaluate the influence of age on prolactin action, and (3) further investigate the mechanisms of prolactin action on calcium absorption. The intestinal calcium absorption in mature rats was evaluated by measuring the plasma 45Ca content at intervals during a 1-h period following intragastric administration of a 45Ca-containing test solution and by measuring tibial 45Ca content in weaned rats. By using weaned (50–70 g), sexually mature (180–200 g) or aged (> 250 g) female Wistar rats, we demonstrated that calcium absorption was inversely related to age. Prolactin at a dose of 0.02 mg/100 g body weight, administered intraperitoneally 1 h before Ca administration, significantly enhanced calcium absorption in sexually mature and weaned rats but not in aged rats. At a luminal calcium concentration of 5 mM, prolactin had no effect when the luminal solution was either CaCl 2 alone or an Na-free electrolyte solution. On the other hand, prolactin significantly increased the plasma 45Ca content by 57, 42 and 28% at 5, 15 and 30 min respectively, when the electrolyte solution contained sodium. In contrast, in the presence of 0.5 mM calcium, the enhancing effect of prolactin on calcium absorption was not dependent on the presence of sodium. Compared with the saline control, the plasma 45Ca content in prolactin treated animals was significantly elevated by 63% at 5 min when the test solution was a sodium-free electrolyte solution.

Effect of cadmium on vitamin D-non-stimulated intestinal calcium absorption in rats

The present report demonstrates the effect of Cd on intestinal Ca transport and Ca-binding protein in rats adapted to vitamin D repletion and high Ca. There were significant decreases in in vitro intestinal Ca transport in animals exposed to Cd for 2 or 3 months as compared with controls. Ca transport from everted gut sacs of normal rats showed a dose-dependent decrease. 45Ca-binding activity to intestinal mucosa from Cd-exposed rats showed a lower level of decrease than that on control rat mucosa. The typical peak of Cd-binding protein obtained from Sephadex G-100 gel filtration of 109Cd added to mucosal supernatant agreed with results of gel filtration obtained after 45Ca had been added to the same supernatant. Although there were 2 proteins binding Cd or Ca in the intestinal mucosa, with the same molecular weight of 10 000, these proteins were shown to be different, since Cd did not bind with the Ca protein. It was concluded that inhibition of vitamin-D-non-stimulated Ca transport was not caused by Cd bound to Ca-binding protein, but by some other factor.

Effects of chlorothiazide on 1,25-dihydroxyvitamin D3, parathyroid hormone, and intestinal calcium absorption in the rat.

Previous studies have shown that thiazide diuretic agents reverse secondary hyperparathyroidism and reduce circulating 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and intestinal calcium absorption rates in patients with idiopathic hypercalciuria of the renal-leak variety. We have investigated whether thiazides can reverse the secondary increase in serum parathyroid hormone (PTH) and 1,25(OH)2D3 levels or intestinal calcium absorption induced by feeding rats a diet low in calcium (LCD, 0.02% calcium) but adequate in phosphorus and vitamin D. We found that LCD increased circulating immunoreactive PTH [chow vs. LCD, 0.52 +/- 0.06 vs. 1.06 +2- 0.1 (SE) ng/ml, P less than 0.001], 1,25(OH)2D3 (chow vs. LCD, 101 +/- 15 vs. 325 +/- 38 pg/ml, P less than 0.001), calcium uptake by everted gut sacs from duodenum, ileum, and descending colon, and net calcium absorption by descending colon studied in Ussing chambers in vitro. Chlorothiazide (CTZ) prevented the increase in PTH during LCD (chow + CTZ vs. LCD + CTZ, 0.69 +/- 0.07 vs. 0.73 +/- 0.06, NS) but not the increase in 1,25(OH)2D3 (chow + CTZ vs. LCD + CTZ, 88 +/- 10 vs. 277 +/- 31, P less than 0.002) or intestinal calcium transport. The drug caused no change in serum 1,25(OH)2D3 or intestinal calcium absorption in rats fed normal chow. In rats given exogenous 1,25(OH)2D3 to stimulate intestinal calcium absorption, CTZ reduced urine calcium excretion greatly but did not alter intestinal calcium absorption.

The mechanism of the action of growth hormone on vitamin D metabolism in the rat.

GH has been shown to stimulate intestinal calcium absorption in rats and humans. We have investigated in rats whether GH might affect intestinal calcium absorption by stimulating the production of 1,25-dihydroxyvitamin D3 [1,25-(OH2D3], the active metabolite of vitamin D3. The tissue distribution of [3H]1,25-(OH2D3 8-40 h after iv injection of [3H]25-hydroxyvitamin D3 ([3H]25OHD3) was measured in sham controls, hypophysectomized, and GH-treated hypophysectomized rats. Since the plasma disappearance rate of iv [3H]1,25-(OH)2D3 was not significantly affected by hypophysectomy, the recovery of [3H]1,25-(OH)2D3 after [3H]25OHD3 administration was taken to be an indirect measure of renal 25-OHD3-1-hydroxylase. Hypophysectomy was found to reduce the recovery of [3H]1,25-(OH)2D3 from serum and intestinal mucosa by 70 +/- 2% (range). A 6-day course of GH treatment of hypophysectomized rats restored the formation of 1,25-(OH)2D3 to normal, and a significant effect was noted within 2 days, before any increase in renal weight was detectable. No other pituitary hormones appeared to be necessary. The markedly atrophic intestinal mucosa of hypophysectomized rats incorporated iv [3H]1,25-(OH)2D3 normally. However, it remains to be determined whether 1,25-(OH)2D3 alone can correct the decreased calcium transport in hypophysectomized rats.

Inhibitory effect of tin on intestinal calcium absorption in rats

The effect of tin on intestinal calcium absorption was studied in rats given stannous chloride (Sn, 30 mg/kg every 12 hr) orally for 3 days. The increase of serum calcium concentration after a single oral administration of calcium chloride (Ca, 500 mg/kg) was significantly inhibited by the prior administration of tin. Calcium concentrations in duodenal mucosa were also reduced to one-third of control values by the administration of tin. The calcium-binding activity in the supernatant fraction of 38,000 g of the mucosal homogenate was decreased to one-quarter of control values, and alkaline phosphatase activity in the mucosal homogenate was markedly lowered by the administration of tin. These results suggest that the oral administration of tin inhibited the duodenal active transport of calcium.

Effect of 1,25-dihydroxyvitamin D 3 on intestinal calcium absorption in strontium-fed rats

These studies investigated the initial stimulation of intestinal calcium absorption in the rat by 1,25-dihydroxyvitamin D 3. To produce a functional vitamin D 3-deficiency, rats were fed a diet containing 2.4% strontium. After 10 days on the diet, intestinal calcium uptake, as measured by everted gut sacs, was significantly depressed. Strontium-fed rats were dosed orally with 1,25-dihydroxyvitamin D 3, and changes in intestinal calcium uptake, intestinal alkaline phosphatase activity, and intestinal calcium-binding protein were measured as a function of time after dose. Calcium uptake was significantly increased in the proximal 2.5 cm of the duodenum at 4 h and along the whole duodenum by 7 h. Intestinal alkaline phosphatase activity, measured in a Triton extract of the mucosal homogenate and in isolated brush border complexes, was also increased by 7 h. Using both gel electrophoresis and immunodiffusion against a specific antiserum, an increase in intestinal calcium-binding protein was detected in intestinal supernate at 4 h after dosing. Almost no calcium-binding protein was detectable in strontium-fed rats dosed with propylene glycol only. These time studies are consistent with a role for both alkaline phosphatase and calcium-binding protein in the 1,25-dihydroxyvitamin D 3-stimulated uptake of calcium by the intestine. In addition, the usefulness of strontium feeding for producing a functional vitamin D 3 deficiency in rats is demonstrated.

Studies on the active principle of Solanum malacoxylon.

INGESTION of the shrub Solanum malacoxylon Sendtner (syn Solanum glaucum Dun) produces a rapid hypercalcaemia and hyperphosphataemia1, 2 which can result in a general calcinosis in various animals3–7. The effects seem to be due to a large increase in calcium absorption from the diet8 and the condition resembles that of vitamin D'intoxication9. Smith and O'Donell9 showed that oral administration of dried, milled, S. nialacoxylon leaves, 72 and 48 h earlier, produces effects similar to those of cholecalciferol (vitamin D3) on in vitro intestinal calcium absorption in rats. They mention that, although the effects on calcium absorption closely resemble those of cholecalciferol, contrary to what one might expect if the active principle were vitamin D, the activity is soluble in water3.