Effects of excess nicotinamide administration on the urinary excretion of nicotinamide N-oxide and nicotinuric acid by rats

We investigated a useful chemical index for an excessive nicotinamide intake and how this excessive nicotinamide intake affects the tryptophan-nicotinamide metabolism in rats. Weaning rats were fed on a tryptophan-limited and nicotinic acid-free diet containing no, 0.003%, 0.1%, 0.2%, or 0.3% nicotinamide for 21 days. Urine samples were collected on the last day and analyzed the intermediates and metabolites on the tryptophan-nicotinamide pathway. Nicotinamide N-oxide, nicotinic acid and nicotinuric acid, metabolites of nicotinamide, were detected when nicotinamide at more than 0.1% had been taken. An intake of nicotinamide of more than 0.1% increased the urinary excretion of quinolinic acid, an intermediate on the pathway. Nicotinamide N-oxide and nicotinuric acid increased with increasing dietary concentration of nicotinamide. These results show that the measurements of nicotinamide N-oxide and nicotinuric acid in urine would be useful indices for an excessive nicotinamide intake.     

Acute glucocorticoid treatment increases urinary biotin excretion and serum biotin

Previous studies have demonstrated that glucocorticoids alter biotin metabolism. To extend these studies, the effect of dexamethasone on biotin pools was analyzed in rats consuming a purified diet containing a more physiological level of dietary biotin intake (0.06 mg/kg). Acute (5 h) dexamethasone administration (0.5 mg/kg) elicited elevated urinary glucose output as well as elevated urinary biotin excretion and serum biotin. Renal and hepatic free biotin was also significantly elevated by acute dexamethasone administration. Chow-fed rats treated with an acute administration of dexamethasone demonstrated significantly elevated urinary glucose excretion, urinary biotin excretion, and serum biotin, but no change in tissue associated biotin was detected. Chronic administration of dexamethasone (0.5 mg/kg ip) over 4 days significantly elevated urinary glucose excretion 42% but had no effect on urinary biotin excretion, serum biotin, or hepatic- or renal-associated free biotin. These results demonstrate the existence of potentially novel regulatory pathways for total biotin pools and the possibility that experimental models with high initial biotin status may mask potentially important regulatory mechanisms.     

Biotin deficiency and biotin excess: Effects on the female reproductive system

Biotin deficiency and biotin excess have both been found to affect reproduction and cause teratogenic effects. In the reproductive tract, however, the effects of biotin have not been well established yet. We investigated the effects of varying biotin content diets on the oestrus cycle, ovarian morphology, estradiol and progesterone serum levels, and the uterine mRNA abundance of their nuclear receptors, as well as on the activity of the estradiol-degrading group of enzymes cytochrome P450 (CYP) in the liver. Three-week-old female BALB/cAnN Hsd mice were fed a biotin-deficient, a biotin-control, or a biotin-supplemented diet (0, 7.2 or 400 μmol of free biotin/kg diet, respectively) over a period of nine weeks. Striking effects were observed in the biotin-deficient group: mice showed arrested estrous cycle on the day of diestrus and changes in ovary morphology. Estradiol serum concentration increased 49.2% in biotin-deficient mice compared to the control group, while the enzymatic activities of CYP1A2 and CYP2B2 increased (P < 0.05). The mRNA abundance of nuclear estrogen and progesterone receptors decreased in the biotin-deficient mice. In the biotin-supplemented group we found that, in spite of a significant (P < 0.05) decrease in the number of primary and Graafian follicles and in CYP1A2 activities, mice exhibited 105.4% higher serum estradiol concentration than the control group. No changes in the expression of the nuclear receptors were observed. No significant differences were observed in serum progesterone among the groups. Our results indicate that both the deficiency and the excess of biotin have significant effects on the female mouse reproductive system.     

Biotin deficiency and biotin excess: Effects on the female reproductive system

Biotin deficiency and biotin excess have both been found to affect reproduction and cause teratogenic effects. In the reproductive tract, however, the effects of biotin have not been well established yet. We investigated the effects of varying biotin content diets on the oestrus cycle, ovarian morphology, estradiol and progesterone serum levels, and the uterine mRNA abundance of their nuclear receptors, as well as on the activity of the estradiol-degrading group of enzymes cytochrome P450 (CYP) in the liver. Three-week-old female BALB/cAnN Hsd mice were fed a biotin-deficient, a biotin-control, or a biotin-supplemented diet (0, 7.2 or 400 μmol of free biotin/kg diet, respectively) over a period of nine weeks. Striking effects were observed in the biotin-deficient group: mice showed arrested estrous cycle on the day of diestrus and changes in ovary morphology. Estradiol serum concentration increased 49.2% in biotin-deficient mice compared to the control group, while the enzymatic activities of CYP1A2 and CYP2B2 increased (P < 0.05). The mRNA abundance of nuclear estrogen and progesterone receptors decreased in the biotin-deficient mice. In the biotin-supplemented group we found that, in spite of a significant (P < 0.05) decrease in the number of primary and Graafian follicles and in CYP1A2 activities, mice exhibited 105.4% higher serum estradiol concentration than the control group. No changes in the expression of the nuclear receptors were observed. No significant differences were observed in serum progesterone among the groups. Our results indicate that both the deficiency and the excess of biotin have significant effects on the female mouse reproductive system.     

Decrease in urinary excretion of active kallikrein in conscious young and adult spontaneously hypertensive rats

Urinary excretion of active kallikrein was determined every day (amidolytic assay) in 6 male Okamoto-Aoki spontaneously hypertensive rats (SHR) and 6 male normotensive Wistar-Kyoto rats (WKY) from ages 4 to 7 weeks and from 12 to 15 weeks. The rats were housed in individual metabolic cages and were allowed free access to food having normal sodium content and to tap water. Urinary kallikrein excretion was lower in 4-week-old SHR than in age-matched WKY (7.8 +/- 1.4 vs. 15.5 +/- 2.3 nkat/24 h respectively, P less than 0.01) at a moment when systolic blood pressure (BP) in SHR was already higher than in WKY. The slope of the increase in active kallikrein excretion from week 4 to 7 was not different for SHR and WKY (6.34 +/- 1.05 vs. 7.50 +/- 1.02 nkat/24 h-1 . wk-1 respectively). In contrast, from week 12 to 15, this slope was not significant for SHR (1.67 +/- 2.55 nkat/24 h-1 . wk-1) while it remained positive in WKY (7.36 +/- 3,44 nkat/24 h-1 . wk-1). In both SHR and WKY, urinary kallikrein excretion was directly related to BP from week 4 to 7 but the slope of the regression line was less for SHR than for WKY (0.19 +/- 0.05 vs. 0.48 +/- 0.12 nkat/24 h-1 . mm Hg respectively). From ages 12 to 15 weeks, kallikrein excretion was still related to pressure in WKY (y = 1.92 x - 180.8; r = 0.93) but not in SHR (y = 0.71 x - 81.48; r = 0.52).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of chronic isoproterenol administration on beta 1-adrenoceptors and growth of pancreas of young and adult rats

[3H]Dihydroalprenolol (DHA) binding of membranes of adult pancreas differed from that of pancreas of young rats, and the DHA binding in the presence of atenolol or butoxamine also was different in the two age groups. The adult pancreas had 93% beta 2- and 7% beta 1-adrenoceptors and did not exhibit an increased incorporation of [3H]thymidine into deoxyribonucleic acid (DNA) following 2 days of DL-isoproterenol (ISO) administration; in contrast, pancreas of the 20-day-old rat had 71% beta 2-adrenoceptors and 27% beta 1-adrenoceptors and exhibited a 34-fold increase over that of adult, and a 6-fold increase over that of the control 20-day-old pancreas. Acinar cell differentiation was also accelerated by a 7-day regimen of ISO administration from 13 to 20 days of age. These growth responses to ISO appear to be beta 1 mediated. The lack of beta 1-adrenoceptors in the adult may account for the failure of the adult pancreas to exhibit a growth response to ISO.     

Effects of maleic acid administration on urinary excretion of DCEC, and on tissue protein, in the rat

Administration of maleic acid to rats caused increased urinary excretion of S-(1,2-dicarboxyethyl)cysteine [DCEC] and increased binding of maleic acid to tissue proteins. The trichloroacetic acid precipitate from a combined fraction of supernatant and microsome gave the maximum amount of DCEC after hydrolysis. It would appear that aminoaciduria produced by maleate was partially due to increased destruction of some succinylated tissue proteins.     

Relationship of urinary kallikrein excretion to urinary potassium excretion during furosemide administration with and without amiloride

The relationship of urinary kallikrein excretion to urine volume, and to urinary sodium and potassium excretions was studied in normal rats during furosemide diuresis and superimposed injection of amiloride, a K+-sparing diuretic. Continuous infusion of furosemide increased urinary kallikrein, sodium and potassium excretions and the urine volume. Amiloride injection during furosemide diuresis caused further increase in diuresis and natriuresis, but a prompt decrease in urinary kallikrein excretion to basal level, and potassium excretion to below the basal level. The significant correlation of urinary kallikrein excretion to urinary potassium excretion, but not to urine volume and urinary sodium excretion after amiloride injection suggests that the major determinant of urinary kallikrein excretion is renal potassium secretion through a mechanism that is affected by amiloride.     

Lead increases urinary zinc excretion in rats

The major purpose of this study was to determine whether acute or chronic Pb exposure would increase urinary excretion of zinc in the rat. Four groups of unanesthetized rats were given 0, 0.03, 0.3, or 3 mg Pb (as acetate) kg intravenously, and urinary excretion of zinc, sodium, and potassium was monitored for 6 h. Only at the highest dose was urinary Zn excretion significantly elevated; there were no significant changes in sodium and potassium excretion at any dose. Two other groups of rats were studied for 9 weeks in metabolism cages before and during administration of either 500 ppm Pb (as acetate) or equimolar Na acetate in the drinking water. Two days after Pb treatment and continuing through day 35, Zn excretion was elevated in the Pb-exposed animals; beyond this day, zinc excretion became similar in the two groups. The difference in Zn excretion was not the result of lower water intake by the Pb-treated animals. At sacrifice (70 days after starting Pb exposure), Pb-exposed animals had lower Zn content of the plasma and testis, but there was no difference in kidney Zn. Plasma renin activity was significantly higher in Pb-exposed animals. We conclude that chronic Pb exposure in rats can result in some degree of decreased tissue zinc, which is, at least in part, secondary to increased urinary losses of zinc.