Induction of renal senescence marker protein-30 (SMP30) expression by testosterone and its contribution to urinary calcium absorption in male rats

The applicability of stable strontium as a marker for measuring intestinal calcium absorption is mainly dependent on the validity of the assumption that calcium and strontium are absorbed with a constant ratio. Up to now, it is not clear whether this ratio is affected by intervention therapy. Therefore, preclinical screening of this ratio before and after treatment is indispensable for a clinical calcium absorption test based on the use of stable strontium as a marker. We studied the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D(3)], a potent enhancer of active intestinal calcium absorption, on the pharmacokinetics of both calcium-45 and strontium in adult male rats, in a short-term dose-finding study [0-50 ng 1,25(OH)2D(3)/100 g body weight] and also in a placebo-controlled study in which 12.5 ng 1,25(OH)2D(3)/100 g body weight were applied to assess the long-term pharmacokinetics. The mean bioavailability (true absorption) was 33% for calcium and 19% for strontium (ratio 1.7:1), whereas, after 1,25(OH)2D(3) pretreatment, it was 73 and 43% (ratio 1.7:1), respectively. These findings demonstrate that intestinal strontium absorption has, like intestinal calcium absorption, an active component. Moreover, they underscore the applicability of stable strontium as a tool for investigating calcium absorption under various conditions.

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Action of 1,25-dihydroxyvitamin D3 and a diphosphonate on calcium metabolism in rats

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1975.229.2.402 ◽

1975 ◽

Vol 229 (2) ◽

pp. 402-408 ◽

Cited By ~ 34

Author(s):

JP Bonjour ◽

U Trechsel ◽

H Fleisch ◽

R Schenk ◽

HF DeLuca ◽

...

Keyword(s):

Calcium Metabolism ◽

Calcium Absorption ◽

Bone Mineralization ◽

Concomitant Administration ◽

Urinary Calcium ◽

Intestinal Calcium Absorption ◽

Bone Morphology ◽

Dihydroxyvitamin D3 ◽

Calcium Retention ◽

Endogenous Production

The effect of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) on Ca balance, 45Ca kinetics, and bone morphology has been studied in control rats and rats given disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), 10 mg P/kg sc per day. This large dose of EHDP is known to inhibit bone mineralization and intestinal calcium absorption and to depress the endogenous production of 1,25-(OH)2D3. In conctrol rats, 1,25-(OH)2D3 increased intestinal calcium absorption. However, in contrast to the enhanced calcium absorption that results from an augmentation of dietary calcium, the 1,25(OH)2D3-induced augmentation of calcium absorption does not lead to a rise in calcium retention, the intestinal effect being matched by an increased excretion of urinary calcium. The EHDP-induced decrease of intestinal calcium absorption could be completely prevented by the concomitant administration of 1,25-(OH)2D3 but not the inhibition of bone mineralization. Therefore, in contrast to the impairment of calcium absorption, that of bone mineralization brought about by large doses of EHDP cannot be merely attributed to a decreased production of 1,25-(OH)2D3.

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Mechanism of chronic hypocalciuria with chlorthalidone: reduced calcium absorption

AJP Renal Physiology ◽

10.1152/ajprenal.1984.247.5.f746 ◽

1984 ◽

Vol 247 (5) ◽

pp. F746-F752 ◽

Cited By ~ 5

Author(s):

D. A. Bushinsky ◽

M. J. Favus ◽

F. L. Coe

Keyword(s):

Serum Calcium ◽

Calcium Absorption ◽

Chronic Administration ◽

Intestinal Calcium Absorption ◽

Male Rats ◽

Calcium Excretion ◽

Urine Calcium ◽

X 24 ◽

Filtered Load ◽

Urine Calcium Excretion

Chlorthalidone, like other benzothiadiazides, lowers urine calcium excretion chronically. If intestinal calcium absorption did not fall or bone accretion did not increase, serum calcium and the filtered load of calcium would increase and urine calcium would return to pretreatment levels. To determine whether overall intestinal calcium absorption fell, we fed chlorthalidone (5 mg X kg body wt-1 X 24 h-1) to 10 adult male rats eating 15 g/day of a 0.6% calcium diet. Compared with 10 control rats, chlorthalidone reduced urine calcium [2.1 +/- 0.1 (SE) vs. 5.8 +/- 0.5 mg/6 days; P less than 0.001]. Fecal calcium rose (307 +/- 9 vs. 257 +/- 12; P less than 0.005) because percent intestinal calcium absorption fell (41 +/- 2 vs. 52 +/- 2; P less than 0.002). Twenty other rats given the same diet were injected subcutaneously with 1,25(OH)2D3 (50 ng/day). In these rats, chlorthalidone reduced urine calcium (23 +/- 3 vs. 59 +/- 3; P less than 0.001) and percent intestinal calcium absorption (60 +/- 1 vs. 66 +/- 1; P less than 0.01). With or without 1,25(OH)2D3, chronic administration of chlorthalidone reduces intestinal calcium absorption, and this reduction seems to be the mechanism that permits urine calcium excretion to remain low.

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The Measurement of Intestinal Calcium Absorption by External Radioisotope Counting: Application to Study of Nephrolithiasis

Clinical Science ◽

10.1042/cs0390095 ◽

1970 ◽

Vol 39 (1) ◽

pp. 95-106 ◽

Cited By ~ 65

Author(s):

M. R. Wills ◽

E. Zisman ◽

J. Wortsman ◽

R. G. Evens ◽

C. Y. C. Pak ◽

...

Keyword(s):

Calcium Absorption ◽

Scintillation Counter ◽

Renal Stones ◽

Normal Subjects ◽

Total Radioactivity ◽

Urinary Calcium ◽

Intestinal Calcium Absorption ◽

Absolute Amount ◽

Calcium Load ◽

Fractional Calcium Absorption

1. Gastro-intestinal absorption of calcium was studied in man by the measurement of forearm radioactivity in a large-volume liquid scintillation counter following separate oral and intravenous doses of 47CaCl2. From the ratio of the percentages of total radioactivity appearing in the forearm following these separate determinations the fractional absorption of calcium was estimated. 2. Changes of forearm radioactivity with time following the administration of this isotope were studied; evidence is presented that the radioactivity in the forearm at 4 h after administration of the isotope gives a valid assessment of fractional calcium absorption. 3. Fractional calcium absorption determined by this technique correlated well with the net calcium absorption as determined from stool radioactivity after oral administration of isotope. 4. In normal subjects it was shown that fractional calcium absorption measured by this technique varies inversely with the stable calcium load and that the absolute amount of calcium absorbed from given loads increases with the size of the load in the range 20–1000 mg calcium. 5. Gastro-intestinal calcium absorption was measured at various oral calcium loads in a group of fifteen patients with recurrent calcium-containing renal stones. All the patients were normocalcaemic; some had hypercalciuria. In the patients with hypercalciuria, calcium absorption, fractional and absolute, was significantly increased at all calcium loads as compared to that of patients with normal urinary calcium. 6. It is concluded that hyperabsorption of calcium from the gastro-intestinal tract plays a crucial role in the aetiology of hypercalciuria, probably by causing an increase in the renal filtered calcium load.

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Acute Versus Chronic Effects of Whey Proteins on Calcium Absorption in Growing Rats

Experimental Biology and Medicine ◽

10.1177/153537020523000804 ◽

2005 ◽

Vol 230 (8) ◽

pp. 536-542 ◽

Cited By ~ 17

Author(s):

Yongdong Zhao ◽

Berdine R. Martin ◽

Meryl E. Wastney ◽

Linda Schollum ◽

Connie M. Weaver

Keyword(s):

Whey Protein ◽

Bone Mineral ◽

Calcium Absorption ◽

Whey Proteins ◽

Dietary Calcium ◽

Male Rats ◽

Whey Protein Concentrate ◽

Dietary Calcium Intake ◽

Protein Concentrate ◽

Chronic Effects

The acute and chronic effects of whey proteins on calcium metabolism and bone were evaluated. In acute studies, 8-week-old male rats were gavaged with 50 mg whey protein concentrate (WPC) and 25 mg calcium. 45Ca was administered intravenously or orally. Kinetic studies were performed, and femurs were harvested. Four of seven WPCs significantly increased femur uptake of 45Ca compared with controls. One WPC at 50 mg enhanced calcium absorption over a range of calcium Intakes from 35.1 ± 9.4% to 42.4 ± 14.0% (P < 0.01). Three of the most effective WPCs were tested further in a chronic feeding study. One hundred 3-week-old rats were randomly divided into four adequate dietary calcium (ADC; 0.4% Ca) groups (control of 20% casein and three WPC groups with 1% substitution of casein with each of three WPCs) and two low calcium (LC; 0.2% Ca) groups (control of 20% casein and one WPC group with 1% substitution of casein with one WPC). After 8 weeks, there was no effect of WPCs on femur uptake of 45Ca among ADC groups and there was no effect of WPCs on calcium retention, femur breaking force, femur bone mineral density, or total femur calcium at either dietary calcium intake. However, whole body bone mineral content (BMC) was significantly higher (P < 0.05) in the three whey protein concentrate ADC groups compared with the ADC control group. Total BMC at the proximal tibia in whey protein ADC groups was increased, as shown by peripheral quantitative computed tomography. Our results indicate that the acute calcium absorption–enhancing effect of whey proteins did not persist through long-term feeding in rats. However, the initial enhancement of calcium absorption by whey protein was sufficient to Increase BMC.

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Mechanism of the regulation of the 1α,25-dihydroxyvitamin D3 receptor in the rat jejunum by glucocorticoids

Journal of Endocrinology ◽

10.1677/joe.0.1030295 ◽

1984 ◽

Vol 103 (3) ◽

pp. 295-300 ◽

Cited By ~ 10

Author(s):

S. D. H. Chan ◽

D. K. H. Chiu ◽

D. Atkins

Keyword(s):

Calcium Absorption ◽

Male Rats ◽

D3 Receptor ◽

Dexamethasone Treatment ◽

Glucocorticoid Treatment ◽

Dihydroxyvitamin D3 ◽

Adrenal Hormones ◽

Dihydroxyvitamin D ◽

Receptor Number ◽

Crypt Cells

ABSTRACT The distribution of 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3) receptors in isolated jejunal villous and crypt cells was investigated in normal and adrenalectomized male rats, and also in animals treated with the synthetic glucocorticoid, dexamethasone, and/or the glucocorticoid antagonist, 11-deoxycortisol. Adrenalectomy caused an increase in 1,25-(OH)2D3 receptors whilst dexamethasone treatment led to a reduction in receptor number. 11-Deoxycortisol was able to reverse the 'down-regulation' effect caused by glucocorticoids. In all cases, the changes in receptor numbers were more pronounced in crypt cells. The data suggest that, in the small intestine, glucocorticoids may control the synthesis of 1,25-(OH)2D3 receptors via the mediation of a glucocorticoid receptor, and that the adrenal hormones mainly express their effect in crypt cells. It is proposed that this phenomenon may, in part, explain the reduction in calcium absorption which occurs in man after chronic glucocorticoid treatment. J. Endocr. (1984) 103, 295–300

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Verapamil induces PTH resistance but increases duodenal calcium absorption in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1988.255.5.e702 ◽

1988 ◽

Vol 255 (5) ◽

pp. E702-E707 ◽

Cited By ~ 1

Author(s):

J. Fox

Keyword(s):

Vitamin D ◽

Calcium Absorption ◽

Young Male ◽

Significant Negative Correlation ◽

Male Rats ◽

Vitamin D Metabolism ◽

Dose Dependent ◽

Pth Resistance ◽

Oral Verapamil

In vitro, verapamil inhibits duodenal Ca absorption, parathyroid hormone (PTH) secretion, and PTH-stimulated bone resorption. This study was designed to determine if any effects of chronic oral verapamil treatment on PTH secretion-action are reflected by changes in vitamin D metabolism, duodenal Ca absorption, and bone Ca content. Rats (100 g) received verapamil in the drinking water at doses of 4, 20, or 100 mumol.kg-1.day-1 for 2 wk. Verapamil administration did not significantly affect growth, plasma Ca or phosphate, or bone Ca content. However, verapamil treatment was associated with a dose-dependent 90% increase in plasma PTH levels. The elevated PTH was accompanied by a 22% decrease in 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels, such that there was a significant negative correlation (r = -0.52; P less than 0.01) between PTH and 1,25(OH)2D3 levels. Despite the decreased plasma 1,25(OH)2D3 levels, verapamil treatment was associated with a dose-dependent increase in duodenal Ca absorption. The increased Ca absorption did not seem to be caused by a verapamil-induced increased intestinal sensitivity to 1,25(OH)2D3, since verapamil-treated vitamin D-deficient rats showed the same absorptive response to administered 1,25(OH)2D3 as untreated rats. Thus chronic oral verapamil treatment induces an apparent PTH resistance but does not appear to have major effects on overall Ca homeostasis in young male rats.

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Calcium metabolism in dairy sheep

The Journal of Agricultural Science ◽

10.1017/s0021859600042143 ◽

1984 ◽

Vol 102 (3) ◽

pp. 601-608 ◽

Cited By ~ 2

Author(s):

S. Economides

Keyword(s):

Calcium Intake ◽

Calcium Metabolism ◽

Dry Matter ◽

Calcium Absorption ◽

Urinary Calcium ◽

Calcium Balance ◽

Dairy Sheep ◽

Deficient Diet ◽

Pregnant Sheep ◽

Calcium Loss

SummaryCalcium metabolism in dairy sheep was studied using radioisotope and balance techniques. The rate of calcium absorption increased, but the efficiency of calcium absorption decreased, with increasing calcium intake in dry sheep. Endogenous faecal and urinary calcium losses, and the rate of calcium absorption, decreased, but the efficiency of calcium absorption increased in pregnant sheep given a calcium-deficient diet. The rate and the efficiency of calcium absorption and the calcium balance of lactating ewes were not influenced by the prepartum level of calcium intake, when calcium intake in early lactation was high. Endogenous faecal calcium loss was related to dry-matter intake, and total faecal calcium loss was related to calcium intake.

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Mechanism of chronic hypercalciuria with furosemide: increased calcium absorption

AJP Renal Physiology ◽

10.1152/ajprenal.1986.251.1.f17 ◽

1986 ◽

Vol 251 (1) ◽

pp. F17-F24 ◽

Cited By ~ 2

Author(s):

D. A. Bushinsky ◽

M. J. Favus ◽

C. B. Langman ◽

F. L. Coe

Keyword(s):

Calcium Absorption ◽

Chronic Administration ◽

Urinary Calcium ◽

Intestinal Calcium Absorption ◽

Calcium Excretion ◽

Calcium Balance ◽

Urine Calcium ◽

Calcium Diet ◽

Filtered Load ◽

Urine Calcium Excretion

Furosemide produces chronic hypercalciuria. The source of the additional urinary calcium is not known but must be either bone mineral or calcium absorbed by the intestine. Without bone calcium dissolution or increased absorption the filtered load of calcium would fall and urinary calcium excretion would return to pretreatment levels. To determine whether furosemide alters intestinal calcium absorption, we fed furosemide (75 mg . kg body-1 wt . day-1) to 11 rats eating 15 g/day of a 0.60% calcium diet. Compared with 11 control rats, furosemide increased urine calcium (15.6 +/- 0.8 mg/5 days vs. 4.1 +/- 0.3, P less than 0.001). Fecal calcium excretion fell (194 +/- 7 mg/5 days vs. 223 +/- 12, P less than 0.05), indicating an increase in intestinal calcium absorption sufficient to sustain the hypercalciuria. The increase in absorption occurred without an increase in the level of serum 1,25-dihydroxycholecalciferol (180 +/- 20 pg/ml vs. 220 +/- 16, furosemide vs. control, respectively, P = NS). To determine whether the intestinal effect of furosemide persists after the initial sodium diuresis abates, we analyzed only the last 3 days of balance. Again, rats fed furosemide had increased urine excretion and intestinal absorption of calcium, so that net calcium balance was not different from that of controls. Twelve additional rats were fed a 0.02% calcium diet to which 35 mg . kg body wt-1 . day-1 of furosemide was added. Compared with eleven controls, urine calcium increased and fecal calcium excretion again fell, but balance was not different. Chronic administration of furosemide increases intestinal calcium absorption enough to permit urine calcium excretion to remain elevated without the necessity for bone dissolution.

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