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PubMed2005

Aconitase is the main functional target of aging in the citric acid cycle of kidney mitochondria from mice.

The activities of the citric acid cycle enzymes were determined in mitochondria isolated from kidneys of relatively young, middle age, and old mice. Aconitase exhibited the most significant decrease in activity with age. The activity of alpha-ketoglutarate dehydrogenase exhibited a modest decrease in activity, while NADP(+)-isocitrate dehydrogenase (NADP(+)-ICD) activity increased moderately with age. Activities of citrate synthase, NAD(+)-isocitrate dehydrogenase (NAD(+)-ICD), succinyl-CoA synthetase (SCS), succinate dehydrogenase (SD), fumarase (FUM), and malate dehydrogenase (MD) were not affected. The molar ratio of the intra-mitochondrial redox indicator, NADPH:NADP(+), was higher in young compared to old animals, while the NADH:NAD(+) molar ratio remained unchanged. It is suggested that an age-related decrease in aconitase activity along with relatively subtle alterations in activities of some other citric acid cycle enzymes are likely to contribute to a decline in the overall efficiency of mitochondrial bioenergetics. The biological consequences of such alterations include age-related fluctuations in the citric acid cycle intermediates, which are precursors of protein synthesis, activators of fatty acid synthesis, and can also act as ligands for orphan G-protein coupled receptors.

Aconitate Hydratase↗

PubMed1993

Effect of citric acid and maltol on the accumulation of aluminum in rat brain and bone.

Deposition of aluminum in the body is responsible for the development of dialysis-related diseases in patients with renal dysfunction and may play a role in the development of certain neurodegenerative disorders. Although citric acid is known to be a strong enhancer of gastrointestinal absorption of aluminum, its effect on aluminum distribution and accumulation is not yet clear. Maltol has been shown to increase the neurotoxicity of aluminum, but little is known about its effect on aluminum deposition in the body. To elucidate the role of citric acid and maltol in aluminum accumulation and toxicity, rats were loaded intraperitoneally during a 7-day period with different amounts of aluminum chloride in absence or presence of citric acid or maltol before analysis of aluminum in serum, brain, bone, and urine. Coadministration of citric acid led to relatively reduced serum levels, as compared with aluminum and aluminum-maltol treatment. This is explained by both tissue elimination and enhanced renal elimination. Only at the highest aluminum dose (8 mg/kg body weight) was an enhancing effect of citric acid on accumulation of aluminum in brain observed; no effect on bone aluminum was seen. Furthermore, it was seen that citric acid alters the distribution pattern of aluminum. This may be explained by the postulation of a characteristic aluminum citrate species in serum. Administration of citric acid may increase this aluminum fraction in serum, thereby inducing an alteration of the distribution pattern. Maltol was shown to be a strong enhancer of aluminum accumulation in serum, brain, and bone. The rise of aluminum in these target tissues was dose dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

PubMed1981

Biosynthetic and bioenergetic functions of citric acid cycle reactions in Rhodopseudomonas capsulata.

Rhodopseudomonas capsulata can grow in a number of alternative modes, including (i) photosynthetic, defined here as anaerobic growth with light as the energy source, and (ii) heterotrophic, referring to aerobic heterotrophic growth in darkness. The functions of citric acid cycle sequences in these growth modes were investigated using wild-type and appropriate mutant strains. Results of growth tests and O(2) utilization experiments showed that in the heterotrophic mode, energy conversion is dependent on operation of the classical citric acid cycle. Alpha-ketoglutarate dehydrogenase (KGD) activity in wild-type strain B10 is substantially higher in cells grown heterotrophically than in cells grown photosynthetically. Molecular oxygen, even at low concentration, appears to be important in regulation of KGD synthesis and, thus, in expression of citric acid cycle activity. Extracts of (photosynthetically grown) mutant strain KGD11 lack demonstrable KGD activity, and in contrast to the wild type, KGD11 is unable to grow heterotrophically on succinate, malate, or pyruvate owing to failure of the energy conversion function of the citric acid cycle. KGD11, however, grows well photosynthetically on malate or on CO(2) + H(2). The KGD activity level required to support the bioenergetic function of the citric acid cycle is evidently much higher than that necessary to satisfy biosynthetic demands; thus, a very low rate of succinyl-coenzyme A formation (needed for biosynthesis) in the mutant would suffice for growth under photosynthetic conditions. In wild-type R. capsulata, the alpha-ketoglutarate required for glutamate synthesis is ordinarily generated via citric acid cycle reactions, which include the conversions catalyzed by citrate synthase and isocitrate dehydrogenase. Mutants blocked in the former or both of these enzymes can grow photosynthetically if provided with an exogenous source of alpha-ketoglutarate or glutamate, but grow very poorly (if at all) as heterotrophs since the energy supply under these conditions depends on operation of the complete citric acid cycle.

Citrate (si)-Synthase↗

PubMed1993

Citric acid concentration compared to serum parathyroid hormone, 1,25(OH)2D3 and calcitonin during dietary Ca deficiency and rehabilitation enhanced with xylitol in rats.

Young male Wistar rats were fed on a Ca-deficient diet for 3 weeks, after which dietary Ca was restored with either CaCO3 or CaCO3 + xylitol (5% per weight). Citric acid, Ca, Mg, Zn and P were determined in the tibia and femur at the beginning and after 2 and 4 weeks of rehabilitation, and serum and urinary citric acid and serum 1,25(OH)2D3, parathyroid hormone (PTH) and calcitonin were measured at the same points in time. The diminished bone Ca (p < 0.001) after 3 weeks of deficiency did not reduce the bone citric acid concentration, although serum citrate increased markedly. Simultaneously the serum 1,25(OH)2D3 concentration more than doubled and PTH increased (p < 0.01). Rehabilitation with CaCO3 + xylitol reduced the 1,25(OH)2D3 concentration to below the control level (p < 0.05), while serum citric acid remained elevated. CaCO3 alone normalized the elevated hormone and citric acid levels in the serum. Dietary CaCO3 and CaCO3 + xylitol normalized the PTH concentration equally well. The gain in bone Ca after 4 weeks of rehabilitation was significantly greater when xylitol was added compared with CaCO3 alone (p < 0.05). Only the 4-week CaCO3 + xylitol group attained the bone Ca concentration of the controls. Xylitol supplementation seems to affect the serum citric acid concentration independent of 1,25(OH)2D3 and PTH concentrations. The elevated citric acid concentration could be associated with increasing bone Ca.

Animals↗

PubMed1989

Intestinal absorption of aluminum in rats: stimulation by citric acid and inhibition by dinitrophenol.

The effects of citric acid and dinitrophenol on the mucosal uptake of aluminum (Al) and its appearance in the portal and systemic blood were investigated to establish the energy dependence of these processes. Therefore, the rat small intestine was perfused in situ with media containing 20 mmol Al/liter, with or without 5 mmol citric acid/liter, and with or without 0.1 mmol/liter of the metabolic inhibitor DNP. It is concluded that (1) the appearance of Al in systemic blood depends on the mucosal Al uptake after perfusion and the systemic blood level before perfusion and (2) citric acid stimulates and DNP inhibits both mucosal uptake and Al absorption in situ.

Aluminum↗

PubMedDate not supplied

Effect of magnesium trisilicate and citric acid on the biovailability of tetracycline in man.

Oral absorption of tetracycline hydrochloride by human subjects was compared with its absorption when coadministered with magnesium trisilicate, citric acid or magnesium trisilicate-citric acid mixture. Evaluation of the absorption rate was done by means of urinary excretion measurements. The concomitant administration of magnesium trisilicate with tetracycline hydrochloride resulted in a dramatic reduction of the excretion rate of the drug. Ingestion of citric acid with tetracycline showed no significant effect on its absorption. Citric acid administration simultaneously with tetracycline hydrocloride-magnesium trisilicate combination failed to improve the absorption of tetracycline in the presence of magnesium trisilicate contrarily to preveious in vitro results. Conclusions were made that in vitro experiments are not always successful in the prediction of in vivo findings.

Adult↗

PubMed1985

Cerebral citric acid cycle enzymes in methionine sulfoximine toxicity.

The activity levels of pyruvate dehydrogenase, enzymes of the citric acid cycle, aspartate and alanine aminotransferases, and NADP+-isocitrate dehydrogenase were determined in the cerebral cortex, cerebellum, brain stem, corpus striatum, hippocampus, and midbrain regions of normal rats and rats injected with acute and subacute doses of methionine sulfoximine (MSI). In both conditions there was an elevation in the activities of pyruvate dehydrogenase and all the enzymes of the citric acid cycle except malate dehydrogenase, whereas the activities of aminotransferases and NADP+-isocitrate dehydrogenase were suppressed in all the cerebral regions. It is suggested that the operational rates of the citric acid cycle would be enhanced in MSI-induced hyperammonemia and that there might be a derangement in the transport of reducing equivalents across mitochondrial membranes. It has been suggested that the convulsant action of the drug is due to its effects on ionic gradients and may not be due to depletion of alpha-ketoglutarate from the citric acid cycle.

Animals↗

PubMedDate not supplied

Seminal fructose, citric acid and acid phosphatase before and after vasectomy in man.

Seminal fructose, citric acid and acid phosphatase were estimated from 23 healthy males before vasectomy and three months later. Each subject had children and the men volunteered for sterilization because other possibilities of contraception were inapplicable. Vasectomy was performed under local anesthesia in the conventional manner. Semen of all patients was azoospermic three months after vasectomy. In this study, the amounts of seminal fructose and citric acid were significantly higher after vasectomy than before operation. The activity of seminal acid phosphatase was a little less, but the difference was not significant. The increase of seminal fructose and citric acid could be explained by the lack of spermatozoa, which normally use them into their metabolism.

Acid Phosphatase↗

PubMed1985

The effect of citric acid and fibronectin application on healing following surgical treatment of naturally occurring periodontal disease in beagle dogs.

It has recently been suggested that following the exposure of root surface collagen with citric acid, the addition of topically applied fibronectin might promote healing with a fibrous re-attachment. The purpose of this study was to determine the benefit of citric acid demineralization and fibronectin application in the surgical treatment of severe, naturally occurring periodontal disease in Beagle dogs. The 4 treatment modalities employed were: (1) surgery alone (mucoperiosteal flaps); (2) surgery plus fibronectin; (3) surgery plus citric acid; (4) surgery plus citric acid followed by fibronectin application. Coronal and root surface notches were used as biometric and histometric reference points. Final clinical measurements were recorded 6 weeks post surgically, on the day of sacrifice. Significantly increased amounts of connective tissue reattachment were observed in the areas treated with the citric acid/fibronectin combination. Fibrous re-attachment was enhanced at the expense of epithelial downgrowth and occurred directly to both new and old cementum and exposed dentin, often in a functional manner, i.e., perpendicular to the root surface. Areas treated with the surgery and citric acid technique attained moderate amounts of fibrous re-attachment while the other treatment modalities were associated with a long junctional epithelium. The enhanced fibrous re-attachment may be the product of an accelerated coalescing of exposed soft tissue and root surface collagen fibrils, while under the mediating effect of fibronectin.

Animals↗

PubMed1987

Semicontinuous and continuous production of citric acid with immobilized cells of Aspergillus niger.

The citric acid excretion of Ca-alginate-immobilized cells of Aspergillus niger in batch culture decreased with a half-time of approximately 19 days. Reactivation of the biocatalysts by regeneration in growth medium was possible, but it was followed by a submerged sporulation of the fungus, and medium was highly contaminated with free cells. Citric acid production could better be prolonged by semicontinuous cultivation with medium exchange every 7 or 14 days, respectively. After 32 days the remaining activity in semicontinuous culture was 1.4-fold higher than in comparable batch experiments. Similar improvements were obtained with a continuous process at a dilution rate of 0.125 v/v X d, whereby medium efflux kept completely free of detaching mycelia.

Aspergillus niger↗

PubMed2000

Effectiveness of 1 mol L-1 citric acid and 15% EDTA irrigation on smear layer removal.

AIM: The aim of this study was to evaluate in vitro the cleansing and smear layer removal capability of alternate canal irrigation with citric acid and NaOCl. METHODOLOGY: Eighty-one teeth were divided into three groups on the basis of the type of instrumentation, namely, manual stainless steel, Ni-Ti mechanized ProFile .04 taper or MACXim. The groups were further divided on the basis of irrigation protocol: 5% NaOCl alone, NaOCl alternated with 1 mol L-1 citric acid solution or a combination of 15% EDTA and Cetrimide solution. After longitudinal sectioning, dentinal walls were microphotographed with scanning electron microscopy at x300 and x1000 magnifications. Qualitative and quantitative cleansing level evaluations were performed using computerized image analysis software. Data were statistically evaluated using Kruskal-Wallis analysis and t-test. RESULTS: Qualitative evaluation at x300 and x1000 showed no statistically significant differences in cleansing ability between citric acid, EDTA and NaOCl groups. Quantitative evaluation of smear layer removal, measured as open tubules/total dentinal surface ratio, showed that 1 mol L-1 citric acid solution was comparable to EDTA (11.97% vs. 10.36%) (NS); in samples treated with ProFile .04 taper instruments citric acid was most effective (16.17%), whilst in the group treated with manual instrumentation EDTA and Cetrimide were the most effective (11.94%). Specimens irrigated with 5% NaOCl demonstrated significantly more cleansing than those obtained in the other two groups (P < 0.001). CONCLUSIONS: 1 mol L-1 citric acid solution was as effective in removing smear layer as EDTA, but was superior in specimens treated with ProFile .04 taper instruments.

Cetrimonium↗

PubMed1991

Citric acid treatment of periodontitis-affected cementum. A scanning electron microscopic study.

Previous studies have described an inconsistent histological occurrence of a zone of surface demineralization on periodontitis-affected cementum following treatment with citric acid, and a lack of connective tissue attachment to the latter surfaces. In view of these findings, the purpose of the present study was to use scanning electron microscopy to examine the surface morphology of cementum from normal and periodontitis-affected root surfaces following citric acid treatment for differences in the effects of the demineralizing solution on these surfaces. Cementum surfaces were derived from the roots of extracted human teeth from areas beneath attached periodontal ligament fibers (normal) and calculus deposits (periodontitis-affected). 5 specimens were evaluated in both groups. Periodontal ligament fibers were removed from normal root surfaces with a curette, and calculus deposits were removed from periodontitis-affected root surfaces using an ultrasonic scaler. The resultant 5 specimens in each group were then sectioned in half, one-half serving as the untreated control and the other as the experimental, citric acid treated specimen. Experimental specimens were immersed in a saturated solution of citric acid, pH 1 for 3 min and then rinsed in tap water. Both control and experimental specimens were dehydrated in ethanol, critical-point dried, sputter-coated with gold and examined in the scanning electron microscope for morphological characteristics. Citric acid treatment of cementum from normal root surfaces produced an undulating, markedly fibrillar surface morphology which is consistent with the exposure of a fibrillar, collagen substrate. Periodontitis-affected cementum, however, was not appreciably altered in appearance by the citric acid treatment, having only a faint mat-like surface texture. (ABSTRACT TRUNCATED AT 250 WORDS)

Citrates↗

PubMed1991

Influence of aluminum-citrate and citric acid on tissue mineral composition in wether sheep.

A 60-d trial was conducted to determine effects of A1-citrate and citric acid on tissue mineral composition in wether lambs. Eighteen crossbred, yearling wether lambs equipped with ruminal cannulas were fed a diet containing low (.12%) Mg and high (2.87%) K (DM basis) and were allotted to three treatments: 1) control; 2) 2,000 micrograms A1 as A1-citrate/g of diet DM and 3) citric acid equivalent to the citrate in treatment 2. Treatments were administered in 200 ml of deionized water twice daily in divided doses via ruminal cannula. At the end of 60 d, wethers were slaughtered and samples of rib and tibia bone, liver, kidney, brain, spleen, pancreas, parathyroid and pituitary gland were analyzed for mineral concentration. Concentrations of A1 increased (P less than .05) in rib, tibia, liver, kidney, spleen and pituitary gland and tended to increase in brain (P less than .13) in wethers treated with A1-citrate compared to citric acid. Magnesium was decreased in rib (P less than .01) and tended to be decreased in pituitary gland (P less than .15), whereas Ca tended to be decreased in pancreas (P less than .07), kidney (P less than .11) and parathyroid (P less than .10) by A1-citrate treatment compared to citric acid. Potassium decreased (P less than .01) in liver, Fe increased (P less than .05) in kidney, Zn decreased in pituitary (P less than .05) and tended to decrease in pancreas (P less than .10) due to A1-citrate but not citric acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

PubMed1990

Development of a citric acid aerosol as a smoking cessation aid.

The satisfaction derived from smoking depends not only on the pharmacological effects of nicotine but also the sensory stimulation from smoke inhalation, particularly the tracheal 'scratch'. In a previous study, we found that a citric acid aerosol produces a tracheal 'scratch' and provides some of the same satisfaction as cigarette smoke. In the present study, we evaluated a new pocket-sized device for delivering a citric acid aerosol and examined some of the important variables for providing a satisfying substitute for cigarettes. In the first experiment, volunteers who smoked at least 10 cigarettes per day compared a citric acid aerosol (either alone or with flavor additives) to a cigarette and a placebo. The addition of cigarette smoke flavor was found to best enhance the satisfaction provided by the citric acid aerosol. In the second experiment, smokers were given compact citric acid inhalers to use throughout 8 h of cigarette deprivation. The degree of satisfaction was highly correlated with the intensity of throat sensation provided by the aerosol. This citric acid aerosol inhaler may provide a useful tool for smokers while trying to quit smoking.

Aerosols↗

PubMed2000

Citric acid does not improve phosphorus utilization in laying hens fed a corn-soybean meal diet.

Data previously obtained from our laboratory have indicated that citric acid was very effective at improving phytate-P utilization in chicks fed a P-deficient corn-soybean meal (SBM) diet. The objective of the current study was to determine if citric acid would have similar effects in a commercial strain of Single Comb White Leghorn laying hens (n = 432) fed a corn-SBM diet containing 0.10% available P (AP). Dietary treatments were a corn-SBM basal diet (0.10% AP, 3.8% Ca, and 17% CP) supplemented with 0, 1, 2, 3, or 4% citric acid and a positive control diet containing 0.45% AP. Each of the six dietary treatments were fed to six replicate groups of 12 hens from 22 to 40 wk of age. No significant differences in performance were observed among treatments during the first 4 wk of the experiment. Hen-day egg production, feed consumption, feed efficiency, and egg yield were subsequently depressed in hens fed 0, 1, 2, 3, or 4% citric acid compared with hens fed 0.45% AP. The results of this study indicate that citric acid does not improve the utilization of dietary P in laying hens fed a corn-SBM diet containing 3.8% Ca.

Aging↗

PubMed2006

Influence of parenteral fat emulsion Intralipos and citric acid on blood viscosity and erythrocyte morphology in vitro.

In most studies fat emulsion had been administered by enteral route. Recently a parenteral soybean-oil emulsion has been developed. In this study we assessed the effects of a parenteral soybean-oil emulsion (Intralipos) and citric acid on blood rheology and erythrocyte morphology in vitro. Porcine blood was incubated in vitro with increasing concentrations of fat emulsion Intralipos and citric acid at 37 degrees C for 1h. Viscosity of plasma and whole blood was measured using a FASCO-2050 digital viscometer. Red blood cell morphology was examined by light microscopy. The viscosity of whole blood represented an ascending dose-dependence for different Intralipos concentrations at high shear rate of 90 and 225 s(-1), however, it decreased with citric acid concentrations. On the other hand, the whole blood viscosity also declined with citric acid concentrations in presence of 30% Intralipos (v/v), and there is a minimal viscosity at 0.67% citric acid (v/v). There are some thorns on the blood membrane at 40% Intralipos as compared with control (no Intralipos addition), which indicates the Intralipos compound may affect blood cell membranes, and resulted in whole blood viscosity increase. We concluded that the intravenous soybean-oil preparation Intralipos interacts with the erythrocyte membrane, and citric acid could alleviate the whole blood viscosity.

Animals↗

PubMed1993

Clinical evaluation of a citric acid inhaler for smoking cessation.

In this study, we evaluated the efficacy of a hand-held inhaler as an adjunct to a smoking cessation behavioral program. The inhaler delivered a citric acid aerosol with tobacco smoke flavor. Seventy-four smokers were recruited for a 3-week smoking cessation trial. During the first 12 days of the cessation period, smokers used the citric acid aerosol inhaler instead of a cigarette whenever the urge to smoke occurred. The citric acid inhaler significantly reduced CO levels and enhanced rates of smoking abstinence for those with higher than average (34.2 ppm) baseline end-expired carbon monoxide (CO) levels. Craving for cigarettes and negative affect were also alleviated by the citric acid aerosol. These results suggest that the citric acid aerosol may promote successful smoking reduction or cessation in a subgroup of smokers and relieves withdrawal symptoms such as craving for cigarettes, a symptom difficult to treat with currently available nicotine replacement techniques.

Adult↗

PubMed2005

Biocompatibility of EDTA, EGTA and citric acid.

This in vivo study evaluated, through the physicochemical assay method for quantification of enhanced vascular permeability, the irritating potential of EDTA, EGTA, citric acid and saline. Thirty-two male Wister rats were anesthetized and four experimental sites were demarcated on their backs. Injections of 2% Evans blue (20 mg/kg) were administered intravenously into the lateral caudal vein. The test solutions were immediately injected intradermally (0.01 mL) into the experimental sites. The animals were killed 30 min, 1, 3 and 6 h after injection of the solutions and each piece of skin was submerged in formamide and incubated at 45 masculineC for 72 h. After filtration, the optical density was measured in a spectrophotometer and the total amount of dye extracted from the samples was calculated by means of a standard calibration curve. Data were analyzed statistically by two-way ANOVA and Tukey's HSD test. Compared to control, EDTA had the greatest volume of dye followed by EGTA and citric acid, for all time periods. There were statistically significant differences between all solutions (p<0.01). Considering the periods assessed, a significant difference was observed between the 3- and 6-h groups (p<0.05), but not between the 30-min and 1-h groups. Among the organic acids evaluated in this study, citric acid yielded the lowest amount of extracted dye. This indicates that the citric acid was the least irritating solution.

Animals↗