To investigate the effect of dietary Ca levels on metabolic changes of Ca and skeleton in postmenopausal women, 10-month-old ovariectomized female rats were compared with 2 month old rats. The rats were fed either 0.2% or 1.2% Ca diets for 16 weeks. Food intake and weight gain as higher in rats fed high Ca diets and in ovariectomized rats. Apparent Ca absorption as higher, and Ca balance was lower in the low Ca groups. Vertebrae density was higher in old rats or those fed a high Ca diets. The old rats and ovariectomized rats showed decreased bone formation, increased bone resorption and kidney function deterioration resulting in increased urinary Ca excretion. Contradictory to the above observation, old rats and ovariectomized rats still showed higher bone mass and bone ash content. Therefore aging was not fully onging in 10-month-old rats. Bone weights, mineral contents, and mineral/wt ratio were lower in ovariectomized rats. Dietary Ca level did not affect urinary Ca excretion, urinary protein excretion, GFR, serum alkaline phosphatase, or urinary hydroxyporline excretion. This means that dietary Ca level did not influence kidney function or bone turnover. However Ca content and the ash content of femur, 4th vertebra, and scapula were increased in high Ca groups. Therefore, it is considered that decreased bone formation and accelerated bone resorption may account for the increased osteoporotic risk in women in menopause after middle age. However, Ca metabolism can be improved and bone components can be maintained if Ca is supplemented.
Objective: Adriamycin (ADR) is an important anti-cancer drug which can cause renal toxicity. Given the known anti-inflammatory and antioxidant effects of Plantago major (P. major), the aim of this study was to determine the effects of hydroalcoholic extract of P. major on ADR- induced nephropathy in rats. Methods: Fifty male Wistar albino rats were randomly divided into 5 groups including: control, ADR (5 mg/kg), ADR + P. major (600 and 1200 mg/kg) and P. major (1200 mg/kg). The animals were treated with P. major extract for 5 consecutive weeks and ADR was intravenously injected on the 7th day of the study. Urine and serum samples were collected on days 0, 14, 21, 28, and 35 for the measurement of serum cholesterol and albumin levels and urine protein excretion rate. At the end of the study, the left kidneys were removed for apoptosis assessment. Results: Administration of ADR significantly decreased serum albumin level and increased serum cholesterol and urine protein excretion rate as well as, apoptotic cell numbers compared to the control group (P < 0.001) while had no effect on glomerular filtration rate (P > 0.05). Treatment with P. major, in both 600 and 1200 mg/kg doses, increased serum albumin level and decreased serum cholesterol concentration, urine protein excretion rate and as well as the number of apoptotic cell compared to the ADR group (P < 0.001). Conclusion: Our results showed that the P. major extract effectively protects against ADR- induced nephropathy by reducing kidney apoptosis and improving renal functioning in rats.
Lee, Beom-Jin;Parrott, Keith A.;Sack, Robert L.;Ayres, James W.
Journal of Pharmaceutical Investigation
/
v.23
no.3
/
pp.9-18
/
1993
Sugar spheres loaded with melatonin (MT) were coated with $Aquacoat^{\circledR}$ to control the release rate of MT over 8 hours. A zero-order release pattern over 8 hours was obtained with 20% coating on 8-10 mesh beads in USP basket dissolution studies. MT in 20% coated beads was quite stable at room temperature with less than 5% MT degraded during 6 months' storage. Dissolution profiles were also unchanged after 6 months. An oral preparation containing MT-loaded uncoated beads for immediate release and 20% coated beads with $Aquacoat^{\circledR}$ for controlled release over 8 hours was evaluated in six human subjects. When total 0.5 mg MT as low dose (immediate release portion of MT, 0.1 mg) was administered to four subjects, average peak plasma MT concentration was reached at about 600 pg/ml and maintained at about 10 pg/ml over 8 hours. Plasma MT concentration-time profiles were similar in shape to computer-simulated profiles. However, maximal plasma MT concentrations were three times greater compared to computer simulated curve. These results suggest that MT dose, ratio of immediate and controlled release MT, and pharmacokinetic parameters selected are adjusted to mimic endogenous MT concentration-time curve. In another study, 0.2 mg MT having 10% of immediate release portion and 80% controlled release portion produced plasma MT concentration-time curve which is more similar to endogenous profiles. A low bioavailability (<20%) may result from extensive first pass metabolism and remaining amounts of MT from controlled beads. A good correlation between plasma MT concentration and urinary excretion rate of 6-sulphatoxymelatonin (6-STMT), a major metabolite of MT was observed. As plasma MT concentration increased, urinary excretion rate of 6-STMT increased concomitantly. The linear relation between plasma MT and urinary excretion rate of 6-STMT was statistically significant. This result suggests that urinary 6-STMT may be used as an index of circadian rhythms of MT in humans.
Plasma phamacokinetics and renal excretion of theophylline (TP) and its metabolities were ivnestigated in rats. Plasma concentrations of TP declined in a monoexponential manner, while those of 1-methyluric (MU) and 1,3-dimethyluric(DMU) declined in a biexponential manner upon respective iv bolus injection of each compound at 6mg/kg dose. The total body clearances $(CL_r)$ of the metabolites were 4-6 fold larger than that of TP, while the distribution volumes of them at steady-state $(Vd_{ss})$ were 40-50% smaller than that of TP. The metabolites showed their plasma peaks in 30 min after iv injection of TP indicating than that to MU. Renal excretion of TP and its metabolites was studied in urine flow rate (UFR)-controlled rats. The renal clearance $(CL_r)$ of TP was inversely related to pasma TP concentrations, and much smaller than the glomerular filtration rate (GFR) suggesting tubular secretion and profound reabsorption in the renal tubule. The $(CL_r)$ of each metabolite also showed that inverse relationship, but far exceeded GFR suggesting that tubular secretion than GFR by ip injection of probenecid (142.7 mg/kg). It supports that the metabolies are secreted in the renal tubule, and suggests that they share a common transport system in their sectrtion processes with probenecid. On the other hand, the $(CL_r)$ of TP was not affected significantly by the probenecid treatment. Considering the inverse relationship of TP between the $(CL_r)$ and its ploasma concentrations,no effect of probenecid on $(CL_r)$ of TP is most likely due to negligible contribution of the secretion to the overall $(CL_r)$ of TP.
Journal of the Korean Applied Science and Technology
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v.3
no.1
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pp.49-55
/
1986
The purpose of the study was to find an effect of Medium Chain Triglycerids (MCT) diet on cholesterol metabolism in rat. Sprague-Dawley rats were fed two different diets containing MCT(trioctanoate) and corn oil respectively. After feeding to each group for four weeks, the levels of serum and liver cholesterol, the excretion rates of fecal and biliary steroids, and also bile acid composition were investigated. The results obtained from the study are as follows : (1) The average body weight gain in MCT group was almost same as that in the corn oil group. (2) The concentration of serum cholesterol in MCT group was lower than that in the corn oil group. Therefore it is confirmed that the cholesterol lowing action of MCT diet was practically high. (3) The concentrations of liver cholesterol and Triglyceride in MCT group were almost same as that in the corn oil group. Therefore it is thought that the level of liver lipids was not influenced by the difference of diet in this study. (4) The excretion rate of fecal neutral steroid in MCT group was significantly lower than that in the corn oil group, while the rate of fecal bile acid excretion was about same in both MCT and corn oil group. (5) The composition rates of fecal bile acid such as cholic acid, chenodeoxycholic acid and deoxycholic acid, a secondary acid of cholic acid, in MCT group were significantly lower than that in the corn oil group. (6) The excretion rates of biliary cholesterol and bile acid in MCT group were significantly higher than that in the corn oil group, while the composition rates of biliary bile acid such as chenoddeoxycholic acid and deoxycholic acid in MCT group were significantly higher than that in the corn oil group.
This study was performed to determine the effect of three different concentrations of soy-isoflavones on calcium and phosphorus balance in either sham-operated or ovariectomized female rats. Seventy-two 16-week old Sprague-Dawley rats underwent sham operation or bilateral ovariectomy. They were provided diets containing different levels of soy iso-flavones for 6 weeks: 50 ppm (Jow isoflavone intake; LI) , 250 ppm (medium isoflavone intake; MI) and 500 ppm (high isoflavone intake; HI). The subsequent fecal and urinary excretions of calcium and phosphorus were then measured. In the sham-operated rats, body weight gains and food efficiency ratio of the MI and HI groups were significantly lower than the control group while food intake was not different. However, there was no significant difference in the ovariectomized rats. The fecal excretion of calcium was significantly lower in the LI, MI and HI groups than the control group in sham operated rats, and significantly lower in the HI group than the control group in ovariectomized rats. Also, apparent ab-sorption rate of calcium and phosphorus did not show any significant difference among groups. Urinary excretion of calcium and phosphorus was significantly lower in the HI group than the LI group in the sham-operated rats. Urinary excretion of calcium was significantly higher in the control ovariectomized rats than in the control sham-operated rats. Retention of calcium and phosphorus did not show any significant difference in both groups. From the above result, we see that isoflavone intake increases calcium retention through an increase in calcium absorption and also suppresses the increase of calcium excretion in urine in ovariectomy. Therefore, it is suggested that isoflavone intake is recommended for menopausal women who experience sharp bone loss due to the decrease in estrogen honnone.
The influence of prazosin (0.1 mg/kg i.v.) on the excretion and diuretic action of furosemide (2mg/kg i.v.) in rabbits was studied to investigate an interaction between ${\alpha}-adrenergic$ blocking agent, prazosin and furosemide. The results were as follows; 1) With the combined administration of prazosin and furosemide, the plasma concentration of furosemide was increased, the urinary excretion rate and renal clearance of furosemide were reduced, and tile biological half-life of furosemide was increased. 2) The diuretic action of furosemide was significantly reduced with the combined administration of prazosin: maximal decrease in urine volume, urinary electrolytes, clearance of $Na^+$ and $Cl^-$, and GFR and RPF, as well as maximal increase in $Na^+$ reabsorption rate were noted 10 minutes after administration of furosemide (2mg/kg i.v.)
Bethanidine was administered into the lateral ventricle of the rabbit brain for the investigation of the effect on the renal function in doses ranging from 0.1 to 1.0mg/kg. In a dose of 0.1 mg/kg, bethanidine did not exhibit significant changes on the renal function of the rabbit, on the other hand, in the doses of 0.3 and 1.0mg/kg bethanidine elicited the reduction of renal plasma flow and glomerular filtration rate with a marked antidiuresis, at the same time bethanidine produced the decrement of urinary sodium and potassium excretion. After intravenous pretreatment of phentolamine, intraventricular bethanidine in a dose of 0.3mg/kg did not produced the antidiuresis and the decrement of urinary sodium and potassium excretion, wherease renal plasma flow and glomerular filtration rate reduced as before of phentolamine pretreatment although the durations of their reduction were shortened. These observations suggest that bethanidine induces the antidiuresis through the centrally mediated mechanism which interposed other factors in addition to sympathetic stimulation affected by phentolamine, alpha adrenergic blocking agent.
The effect of water temperature on fasting and post-prandial total ammonia excretion (TAN) of the starry flounder Platichthys stellatus (mean body weigh : $42.4{\pm}3.4g$) was studied. The fasting and post-prandial TAN excretions were measured under three different water temperatures (10, 15 and $20^{\circ}C$) for 24 hours using a recirculating system. In each treatment three replicates were set up and total 45 fish were used. Fish were taken to the indoor aquarium, acclimated over 10 days at three temperatures, and transferred to TAN measuring system for measurements of TAN excretion at the same temperatures. After 3 days of starvation, fasting TAN excretion was measured at each temperature. To investigate post-prandial TAN excretion, fish were hand-fed to satiation level with a commercial diet containing 50.2% crude protein for 7 days, two times daily 08 : 00 and 16 : 00 h. The fasting and postprandial TAN excretion increased with increased water temperature (p<0.05). Mean fasting TAN excretion rates at 10, 15 and $20^{\circ}C$ were 10.9, 11.2 and $12.2mg\;TAN\;kg\;fish^{-1}\;h^{-1}$, respectively. The value at $20^{\circ}C$ was higher than those at 10 and $15^{\circ}C$ (p<0.05), but there was no significant difference between $10^{\circ}C$ and $15^{\circ}C$. Mean post-prandial TAN excretion rates at 10, 15 and $20^{\circ}C$ were 33.0, 43.4 and $55.3mg\;TAN\;kg\;fish^{-1}\;h^{-1}$, respectively. Two peaks of post-prandial TAN excretions were observed, and the second peak was always greater than the first. The post-prandial TAN excretion rate reached to the maximum after 10 hours from the first feeding at $10^{\circ}C$($45.3mg\;TAN\;kg\;fish^{-1}\;h^{-1}$), $15^{\circ}C$ ($64.5mg\;TAN\;kg\;fish^{-1}\;h^{-1}$) and $20^{\circ}C$ ($83.2mg\;TAN\;kg\;fish^{-1}\;h^{-1}$), respectively. The TAN loss for ingested nitrogen at $20^{\circ}C$ (48.8%) was higher than that for $10^{\circ}C$ (43.0%) and $15^{\circ}C$ (45.7%). This study provides empirical data for estimating ammonia excretion and managing culture management of starry flounder under given temperatures.
Lithium salts are being used increasingly to treat patient with affective disorders, especially acute mania, or bipolar manic-depressive illness. For therapeutic effect the lithium content must be maintained at or above a particular level. Lithium poisoning due to overdosage may be seen occasionally, and its course is determined primarily by the rate of renal lithium elimination. A search is therefore indicated for procedures that could raise the lithium clearance. In a number of reports renal lithium excretion has been studied in relation to the excretion of water, sodium, potassium and hydrogen, but effects of sodium or water on the lithium excretion has not yet been clarified. Hence the present study was undertaken to investigate the effects of corticosteroid on the excretion of lithium ion. The female rat(Sprague-Dowley), weighing from 200 to 300g, was injected with 50mg/kg of lithium chloride intraperitoneally, and then injected with graded dosage of fludrocortisone and dexamethasone in each group. During the injected rats were incubated in metabolic cage, 24 hour urine of rats were collected. At 24 hours after injection, the rats were sacrificed with guillotin, the blood were collected. And then the concentratios of $Na^+$, $K^+$, $Li^+$ of collected urine and serum were checked by Flame photometer. The results are summarized as follows; 1. Fludrocortisone decreased the serum concentration of lithium and increased the urinary excretion of lithium. 2. In the group treated with low dose of dexamethasone(0.1mg/kg), the serum concentration of lithium was decreased and high dose of dexamethasone (1mg/kg) increased the urinary excretion of lithium. 3. Fludrocortisone increased the urinary $[Na^+]/[K^+]$ in serum and decreased $[Na^+]/[K^+]$ in urine, but opposite effects were occurred in dexamethasone. By above results, it may be concluded that corticosteroid increased the urinary excretion of lithium and decreased the serum concentration of lithium, but it seems to be there is no relationship between these effects of corticosteroid and of the renal $Na^+$ or $K^+$ transport.
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