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PubMed1999

Detection and characterization of boric acid and borate ion binding to cytochrome c using multiple quantum filtered NMR.

The application of multiple quantum filtered (MQF) NMR to the identification and characterization of the binding of ligands containing quadrupolar nuclei to proteins is demonstrated. Using relaxation times measured by MQF NMR multiple binding of boric acid and borate ion to ferri and ferrocytochrome c was detected. Borate ion was found to have two different binding sites. One of them was in slow exchange, k(diss) = 20 +/- 3 s(-1) at 5 degrees C and D(2)O solution, in agreement with previous findings by (1)H NMR (G. Taler et al., 1998, Inorg. Chim. Acta 273, 388-392). The triple quantum relaxation of the borate in this site was found to be governed by dipolar interaction corresponding to an average B-H distance of 2.06 +/- 0.07 A. Other, fast exchanging sites for borate and boric acid could be detected only by MQF NMR. The binding equilibrium constants at these sites at pH 9.7 were found to be 1800 +/- 200 M(-1) and 2.6 +/- 1.5 M(-1) for the borate ion and boric acid, respectively. Thus, detection of binding by MQF NMR proved to be sensitive to fast exchanging ligands as well as to very weak binding that could not be detected using conventional methods.

Animals↗

PubMed1979

Colorimetric determination of boric acid in prawns, shrimp, and salted jelly fish by chelate extraction with 2-ethyl-1,3-hexanediol.

Borate was directly chelate-extracted from foods with 5% 2-ethyl-1,3-hexanediol (EHD) in n-hexane-n-butyl acetate mixture (8 + 2), from which borate was selectively transferred into 1% NaOH, since EHD-chelated boron did not react with curcumin to develop color. Finally, an aliquot of the alkaline solution was acidified with HCl and reacted with curcumin in a rotary evaporator. Color development was increased by heating for 8 min at 80 degrees C under reduced pressure of 16 mm Hg. Frozen shrimp and prawns (peeled and with shells) and salted jelly fish were analyzed by the proposed method. Results were compared with the contemporary official method of Japan based on curcumin reaction on an incinerated sample. Over 90% of the boric acid was recovered by the proposed method when samples were fortified with 20 ppm boric acid. Recoveries were superior to those of the official method especially for shrimp and prawns with shells and salted jelly fish. Detection limit of boric acid is 1 ppm. Moreover, the method requires only about 1 hr for analysis of one sample, making it suitable for routine analysis.

Boric Acids↗

PubMed2004

Molecular details of urease inhibition by boric acid: insights into the catalytic mechanism.

The structure of the complex of urease, a Ni-containing metalloenzyme, with boric acid was determined at 2.10 A resolution. The complex shows the unprecedented binding mode of the competitive inhibitor to the dinuclear metal center, with the B(OH)3 molecule bridging the Ni ions and leaving in place the bridging hydroxide. Boric acid can be considered a substrate analogue of urea, and the structure supports the proposal that the Ni-bridging hydroxide acts as the nucleophile in the enzymatic process of urea hydrolysis.

Binding Sites↗

PubMed1993

Selectivity of boron carriers for boron neutron capture therapy: pharmacological studies with borocaptate sodium, L-boronophenylalanine and boric acid in murine tumors.

Borocaptate sodium (BSH) and L-boronophenylalanine (L-BPA) are two boron carriers used for boron neutron capture therapy (BNCT) in the treatment of glioblastoma and melanoma, respectively. The suitability of these two compounds was evaluated on the basis of pharmacokinetic studies aiming at characterizing their biodistribution, tumor uptake and tumor selectivity. Boric acid was also used as a reference compound since it is nonselective and relatively freely diffusible. The compounds were investigated in two tumor models, a B16 pigmented melanoma and the RIF1 sarcoma. Mice were sacrificed after different boron doses at various post-injection times and tissue and plasma levels measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The proposed minimum effective tumor boron concentration of 15 ppm was achieved in both tumor models for the three compounds tested, although only for L-BPA in the melanoma was this achieved when tumor-plasma ratios were above 1. In the RIF1 model, maximum tumor concentrations of 44 and 31 ppm B were reached after administration of 50 micrograms B/g body weight for boric acid and BSH, respectively. After administration of 12.5 micrograms B/g of L-BPA, maximum concentrations of 15 and 21 ppm were found in the RIF1 and B16 models, respectively. Tumor-plasma ratios (TPR) for BSH remained close to or below unity at all times studied in both tumors. Brain levels of BSH were very low, however, leading to tumor-brain ratios markedly greater than 1 at all times. L-BPA and boric acid showed TPR values above unity in both tumor models, reaching 3.2 in B16.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1996

Benchmark dose analysis of developmental toxicity in rats exposed to boric acid.

Developmental toxicity risk assessment has typically relied on the estimation of reference doses or reference concentrations based on the use of no-observed-adverse-effect levels (NOAELs) divided by uncertainty factors. The benchmark dose (BMD) approach has been proposed as an alternative basis for reference value calculations. In this analysis of the developmental toxicity observed in rats exposed to boric acid in their diet, BMD analyses have been conducted using two existing studies. By considering various end points (rib XIII effects, variations of the first lumbar rib, and fetal weight changes) and various modeling approaches for those end points, the best approach for incorporating all of the information available from those studies could be determined. Particular emphasis has been placed on methods for combining data across studies and for combining potentially related effects (on rib XIII and on the first lumbar rib). The issues of study and end point selection are ones that will arise frequently in the process of estimating reference values. This example of boric acid suggests that the BMD approach provides a reasonable basis for appropriately comparing and combining study data, as opposed to ad hoc combinations of study results. Moreover, it is shown that the BMD approach can be used with combinations of end points considered to differ in severity. In this case, the preferred approach involved combining the data from the two studies, which were similarly designed and were conducted in the same laboratory, to calculate BMDs that were more accurate and more precise than those that could be derived from either study alone. It was determined that decreased fetal body weight provided the best basis for BMD calculations; BMDs calculated for fetal body weight changes were less than those for all other relevant end points. The appropriate BMD to use as the basis for boric acid reference dose calculation appears to be 59 mg/kg/day, which is very similar to the NOAEL observed in the second of the two studies (55 mg/kg/day). Although the first study failed to establish a NOAEL, the BMD approach could have been applied to that study, thereby avoiding the need for a repeat study. Similar BMD results were obtained in both studies.

Animals↗

PubMed2001

[Investigation of the pharmacodynamic properties of the solution of boric acid].

By virtue of experimental investigations that had been carried out on animals an essential biological action of the aqueous solution of boric acid on the organism could be stated. The solution containing 274.46 mg of H3BO3 in a litre, administered to rats for 30 days orally in an "ad libitum" dose, caused changes in the lipid metabolism and in the water-mineral balance of the organism and in the acid-base equilibrium of the blood, it did not affect the morphology and the parameters of carbohydrate and protein metabolism. No influence has been stated of the investigated boric acid, as used in guinea pigs, on the excretion of bile. Suitably diluted with a nutritive fluid the solution acted spastically on the peristalsis of the small intestine of the rabbit.

Absorption↗

PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 23). A comparative 2- and 4-week repeated oral dose testicular toxicity study of boric acid in rats.

To assess the validity and limitations of 2-week repeated daily dosing to detect toxic effects on male reproductive organs in rodents, a comparative 2- and 4-week oral repeated dosing study of boric acid, a known testicular toxicant, was given to 6- or 8-week-old Crj:Wistar rats at daily levels of 0, 125, 250 and 500 mg/kg. The ages of the rats were selected so that they were all sacrificed at 10 weeks of age. The testes and epididymides were weighed at necropsy; histopathological specimens were prepared in a routine manner and stained with H&E or PAS-H. In addition, the sperm number and motility rates were evaluated. There were no boric acid-induced effects on reproductive organ weights and on gross behavior/appearance in any groups in either the 2- or 4-week studies. The sperm number and motility rate were not decreased in any group after 2 weeks, while both decreased in the 250 and 500 mg/kg groups after 4 weeks. Histopathologically, as evidence of toxicity at the early stage of boric acid exposure, retention of step 19 spermatids of stages IX-XI was observed in the testes of almost all rats treated with 500 mg/kg after both 2 weeks and 4 weeks. Degenerative/necrotic germ cells and multinucleated giant cell formation were observed in 2 weeks, though to a lesser extent than in 4 weeks. On stage analysis of germinal cells in 2 weeks, spermatogonia and spermatids of stage VII were found to be decreased, and pachytene spermatocytes of stage X were increased. In conclusion, the results indicate that if the selection of doses is appropriate, testicular toxicity of boric acid can be detected even after only 2 weeks of repeated daily oral treatment.

Administration, Oral↗

PubMedDate not supplied

Evaluation of a reproductive toxicity assay using Xenopus laevis: boric acid, cadmium and ethylene glycol monomethyl ether.

Cadmium (Cd), boric acid (BA) and ethylene glycol monomethyl ether (EGME) were evaluated for reproductive and developmental toxicity in Xenopus laevis. Eight reproductively mature adult male and eight superovulated female Xenopus laevis were exposed to at least five separate sublethal concentrations of each material via the culture water for a period of 30 days. Four respective pairs were mated and the offspring evaluated for developmental effects; an evaluation of reproductive status was performed on the remaining four specimens. Ovary pathology, oocyte count, oocyte maturity and maturation capacity (germinal vesicle breakdown, GVBD) and necrosis were evaluated in the female, whereas testis pathology, sperm count, dysmorphology and motility were studied in the male. Based on this assessment, each test material exerted reproductive toxicity in Xenopus laevis, but with varying potencies. Adult female exposure to Cd and EGME particularly, and to a lesser extent to BA, resulted in transgenerational toxicity to the developing progeny. Further, this model appears to be a useful tool in the initial assessment and prioritization of potential reproductive toxicants for further testing.

Abnormalities, Drug-Induced↗

PubMed1990

[Treatment of deep wounds with loss of tissue. Value of a 3 percent boric acid solution].

Following the finding of dramatic improvement in a deep wound with loss of substance treated with a 3 percent boric acid solution, 31 patients hospitalized in a surgical intensive care unit and holding such a wound initially unimproved by classical treatments were subjected, in 1987-88, to a short-time use of this solution. A case-control study retrospectively performed with 12 of the patients demonstrated that after wound granulation was obtained they returned to a normal care unit about three times more rapidly than patients receiving conventional antiseptics (means: 20 and 55 days respectively). This reduction in intensive care duration of stay for these 12 patients saved approximately 2 millions francs. Thus, the 3 percent boric acid solution may be considered an efficient alternative in the treatment of deep wounds with loss of substance, but it is delicate to handle because of toxicity.

Adolescent↗

PubMed2002

Boric acid susceptibility testing of non-C. albicans Candida and Saccharomyces cerevisiae: comparison of three methods.

To establish the best method for boric acid susceptibility testing, we compared two agar dilution methods (high and low inoculum) and a standard broth microdilution method (from the National Commitee for Clinical Laboratory Standards document NCCLS M-27A). Saccharomyces cerevisiae (37) and non-C. albicans Candida (39) isolates, as well as one isolate of Trichosporon sp., were included. All were isolated from female workers with vulvovaginitis. Good agreement within a fourfold dilution range was found between the three methods, and only the broth microdilution method versus the agar dilution method with high inoculum showed significant discrepancies. Reading results was easier with the broth microdilution method than with the agar dilution methods because of partial growth inhibition in the latter. In conclusion, broth microdilution is a suitable method for testing yeast susceptibility to boric acid.

Agar↗

PubMed2006

Effects of sublethal exposure to boric acid sugar bait on adult survival, host-seeking, bloodfeeding behavior, and reproduction of Stegomyia albopicta.

Effects of sublethal exposure to 0.1% boric acid sugar bait on adult survival, host-seeking, bloodfeeding behavior, and reproduction of Stegomyia albopicta were studied in the laboratory. Survival of males as well as females was significantly reduced when exposed to the bait, compared to control adults. The host-seeking and bloodfeeding activities in the baited females decreased, but the mean duration of blood engorgement (probing to voluntary withdrawal of proboscis) was not significantly different between the baited and control females. The landing and biting rates (human forearm) were significantly reduced in the baited females compared to nonbaited controls. Fecundity and fertility (based on number of laid eggs per female and percentage egg hatch, respectively) in the baited females were significantly reduced, and ovarian development was retarded. Sublethal exposure to sugar-based boric acid bait has the potential to reduce adult populations of St. albopicta.

Animals↗

PubMed1982

Improved method for determination of catecholamines in rat brain by isolation on boric acid gel and high-performance liquid chromatography with electrochemical detection.

An improved sensitive, simple and time-saving method for determining catecholamine (CA) in rat brain is described. The method involves isolation on boric acid gel and high-performance liquid chromatography with electrochemical detection. Boric acid gel effectively adsorbs CA at weakly alkaline pH and the over-all recoveries of 5 ng and 10 ng samples of authentic norepinephrine (NE) and dopamine (DA) added to a homogenate of rat brain were 98.9 +/- 9.2% and 103.4 %/- 9.3% for NE and 96.2 +/- 4.6% and 99.4 +/- 4.8% for DA, respectively. Intra-assay variation was 5.3% (5 ng) and 3.0% (10 ng) for NE and 4.4% (5 ng) and 3.8% (10 ng) for DA. Inter-assay variation was 7.7% (1 ng) for NE and 5.0% (1 ng) for DA. With this analytical system, the lowest amount of NE or DA detectable was 40 pg. Application of this method to determination of the DA and NE contents of rat hypothalamus during estrous cycle revealed significant increases in the turnovers of both in the proestrus stage. This method should be useful for routine determination of plasma NE and DA because it is sensitive and inexpensive.

Animals↗

PubMed2005

Mechanism of permeability-enhancing effect of EDTA and boric acid on the corneal penetration of 4-[1-hydroxy-1-methylethyl]-2-propyl-1-[4-[2-[tetrazole-5-yl]phenyl]phenyl] methylimidazole-5-carboxylic acid monohydrate (CS-088).

This study was conducted to clarify the penetration properties of 4-[1-hydroxy-1-methylethyl]-2-propyl-1-[4-[2-[tetrazole-5-yl]phenyl]phenyl]methylimidazole-5-carboxylic acid monohydrate (CS-088), an ophthalmic agent, and the mechanism of the permeability-enhancing effect of EDTA and boric acid (EDTA/boric acid) on the corneal penetration of CS-088. In the absence of additives, corneal permeability decreased with increasing concentration of CS-088 as CS-088 monomers self-associate to form dimers. Presence of EDTA/boric acid caused no significant changes in the physicochemical properties of CS-088, the apparent partition coefficient or the mean particle size of CS-088. EDTA/boric acid induced only a slight change in the zeta potential of liposomes used as a model of the biological membrane. On the other hand, EDTA/boric acid significantly increased membrane fluidity of liposomes, whereas other buffering agents tested did not. This effect was synergistic and concentration-dependent for both EDTA and boric acid as was observed in in vitro corneal penetration of CS-088. In accordance with the result, the rate of CS-088 permeation into the liposomes significantly increased by the addition of EDTA/boric acid. Therefore, it was demonstrated that EDTA/boric acid promotes corneal penetration of CS-088 through the transcellular pathway by increasing membrane fluidity. Conversely, other buffering agents decreased corneal permeability of CS-088 by inducing further self-association of CS-088 aggregates.

1-Octanol↗

PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 24). Testicular toxicity of boric acid after 2- and 4-week administration periods.

To assess whether or not male reproductive toxicity can be evaluated in a 2-week administration study, boric acid was administered daily by oral gavage to male Jcl:Wistar rats at dosage levels of 0, 300 and 500 mg/kg for 2 and 4 weeks, and the results obtained with the two different treatment schedules were compared. After a 2-week administration, decreased testis weights were observed in the 500 mg/kg group. Histopathologically, exfoliation of round spermatids, retention of step 19 spermatids and increased numbers of residual body-like structures in the seminiferous tubules and cell debris in the cranial epididymal ducts were observed in the 300 and 500 mg/kg groups. Distorted cytoplasmic lobes of step 19 spermatids, debris in the seminiferous tubules and focal atrophy of the seminiferous tubules with multinucleated giant cells formation and necrosis of spermatocytes were also observed in the 500 mg/kg group. After a 4-week administration, testis and epididymis weights were decreased in the 300 and 500 mg/kg groups. Histopathological changes in the 300 mg/kg group were similar to those found in the 300 and 500 mg/kg groups after a 2-week administration. Diffuse atrophy of the seminiferous tubules was additionally observed in the 500 mg/kg group. These results suggest that 2 weeks is a sufficient treatment period for the detection of the testicular toxicity caused by boric acid.

Administration, Oral↗

PubMedDate not supplied

The effects of boric acid (BA) on testicular cells in culture.

High-dose boric acid (BA) exposure produces testicular lesions in adult rats characterized by inhibited spermiation that may progress to nonrecoverable atrophy. The mechanism for the testicular toxicity of BA is unknown. To examine possible direct effects, the present study evaluated selected aspects of various testicular cell culture systems after in vitro BA exposure. Specifically, the hallmarks of the BA testicular toxicity were addressed: the mild hormone effect, the initial inhibition of spermiation, and atrophy. No effect of BA on the steroidogenic function of isolated Leydig cells was observed, supporting the contention of a CNS-mediated rather than a direct hormone effect. Since increased testicular cyclic AMP (cAMP) produces inhibited spermiation, and a role for the serine proteases plasminogen activators (PAs) in spermiation has been proposed, we evaluated both Sertoli cell cAMP accumulation in Sertoli-germ cell cocultures and the stage-specific secretion of PA activity in cultured seminiferous tubules after in vitro BA exposure, respectively. The results showed that the inhibited spermiation is not due to BA effects on either process. To address the atrophy, we evaluated BA effects in Sertoli-germ cell cocultures on 1) morphology/germ cell attachment, which might identify a target cell; 2) Sertoli cell energy metabolism, because lactate, secreted by Sertoli cells, is a preferred energy source for germ cells; and 3) DNA/RNA synthesis, because germ cells synthesize DNA/RNA and BA impairs nucleic acid synthesis in liver and may do so in testis. Despite the absence of overt morphologic changes and germ cell loss, the most sensitive in vitro endpoint was DNA synthesis of mitotic/meiotic germ cells, with energy metabolism in Sertoli or germ cells affected to a lesser extent. A re-evaluation of testis sections from rats exposed to BA revealed a decrease in the early germ cell/Sertoli cell ratio prior to atrophy. Thus, although the mechanism for the inhibited spermiation is still undefined and is the subject of future work, these combined studies revealed some changes offering a plausible explanation for the atrophy aspect of the BA testicular lesion.

Animals↗

PubMed2004

Effects of sodium tetraborate and boric acid on nonisothermal mannitol crystallization in frozen solutions and freeze-dried solids.

The purpose of the present study was to elucidate the effects of sodium tetraborate (borax) and boric acid on the crystallization of mannitol in frozen aqueous solutions and freeze-dried solids. Thermal analysis of frozen solutions showed that sodium tetraborate inhibits mannitol crystallization at sodium tetraborate/mannitol molar concentration ratios of approximately 0.05, which is much lower than the other co-solutes studied (boric acid, sucrose, sodium phosphate buffer). Inhibition of the mannitol crystallization in frozen solutions resulted in highly amorphous mannitol in the freeze-dried solids. Mannitol remained in an amorphous state in some of the combination freeze-dried solids, even at elevated temperatures. Changes in the thermal transition temperatures (glass transition temperature of maximally freeze-concentrated solute ( T'g) and glass transition temperature of freeze-dried solid (Tg)) suggested reduced mannitol molecular mobility with increases in the sodium tetraborate ratio. Fourier-transform infrared spectroscopy (FT-IR) analysis of the bovine serum albumin secondary structure showed apparent protein structure-stabilizing effects of the amorphous mannitol and sodium tetraborate combination during the freeze-drying process. The mannitol and sodium tetraborate combination also protected lactate dehydrogenase (LDH) from inactivation during freeze-drying. We conclude that the complex formation and the accompanying reduction in molecular mobility make sodium tetraborate an effective mannitol crystallization inhibitor in frozen solutions and freeze-dried solids.

Animals↗

PubMed1982

Unaffected blood boron levels in newborn infants treated with a boric acid ointment.

No rise in the boron content of the plasma of 22 newborn infants was demonstrated following repeated daily application of a water-emulsifying ointment containing the equivalent of 3% boric acid to the napkin region. The mean plasma-boron concentration fell over 5 days from a pretreatment value of 0.49 to 0.29 mg/litre, the corresponding values in ten untreated neonates being 0.62 and 0.21 mg/litre, respectively. No statistically significant differences were found. The results confirm the safety of such ointments for application to the skin, a conclusion predicted by theoretical estimates of the maximum possible boric acid absorption following application of the ointment.

Boric Acids↗

PubMed2003

Effects of boric acid, fipronil, hydramethylnon, and diflubenzuron baits on colonies of ghost ants (Hymenoptera: Formicidae).

Laboratory colonies of the ghost ant, Tapinoma melanocephalum (F.) were administered sugar solution (10%) baits containing the insecticides boric acid, fipronil (REGENT), hydramethylnon (SIEGE), or diflubenzuron (DIMILN). Colonies were exposed to the baits for 21 d, and development of workers, queens, and brood (larvae and pupae) was observed for 4 wk. Fipronil (0.05%) caused 100% mortality in all colonies the first week. With boric acid (0.5%), 100% mortality of workers, queens, and brood was reached at the end of the third week. With hydramethylnon (2%), 83% of the colonies disappeared at the end of the fourth week, but some queens were still alive 9 wk after the trial started. Diflubenzuron (1%) behaved similarly to the control, although in some colonies, the brood production increased, whereas in other colonies, the queens disappeared. In the control colonies, workers, queens, and brood were always observed even up to 9 wk.

Animals↗