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Biomedical subjects

J Corbella

Publications and source records attributed to J Corbella.

At least 109 records · Page 6Linked to original sources

Sulphur derivative of hexachlorobenzene in human urine.

Pentachlorothiophenol, a sulphur derivative of the widespread environmental pollutant hexachlorobenzene (HCB) has been detected and quantified in the urine of a human general population with high body burden of HCB. The sulphur derivative was analysed by GLC-MS as pentachlorothioanisole (PCTA) after hydrolysis and methylation of the respective conjugate and was found in 100% of the samples (n = 40) with a mean concentration of 1.85 +/- 0.98 ng ml-1 (mean +/- s.d., range 0.58-4.50 ng ml-1). No correlation with urinary pentachlorophenol (PCP) and no sex-related differences were found. The derivative may originate from the biotransformation of HCB stored in tissues and may be a useful maker of HCB metabolism in humans.

Biotransformation↗

Concurrent ingestion of lactate and aluminum can result in developmental toxicity in mice.

The influence of lactate on the potential developmental toxicity of high doses of aluminum (57.5 mg/kg/day) was evaluated. Three groups of pregnant Swiss mice were given by gavage daily doses of Al(OH)3 (166 mg/kg), aluminum lactate (627 mg/kg), or Al(OH)3 (166 mg/kg) concurrent with lactic acid (570 mg/kg) on gestational days 6-15. An additional group of pregnant mice received lactic acid (570 mg/kg) during the same period. Cesarean sections were performed on gestation day 18, and live fetuses were sexed, weighed and examined for morphological defects. Maternal toxicity was observed in the groups treated with aluminum lactate, and Al(OH)3 concurrent with lactic acid. The reproductive data did not show embryotoxic effects in any group, whereas fetal body weight was significantly reduced in the aluminum lactate group. In this group, morphological changes included cleft palate and an increased incidence of parietals with delayed ossification. Although not statistically significant, the incidence of skeletal variations was also increased in the group given Al(OH)3 concurrent with lactic acid. Taken together the present data, as well as the results of previous studies strongly suggest that the consumption of high doses of aluminum-containing compounds should be avoided during pregnancy.

Abnormalities, Drug-Induced↗

Administration of vanadyl sulfate by gavage does not normalize blood glucose levels in streptozotocin-induced diabetic rats.

Vanadyl sulfate trihydrate was given by gavage to streptozotocin-induced diabetic rats for 21 days at doses of 0, 25, 50, or 75 mg/kg/day. In marked contrast to the reduction in plasma glucose observed in diabetic animals given vanadyl sulfate via drinking water, diabetic rats given vanadyl by gavage were not characterized by normoglycemia. Similarly, in contrast to the normalizing effect of vanadyl in drinking water, vanadyl by gavage had only a minimal influence on diabetes associated hyperphagia and polydipsia. Despite the lack of marked effect of vanadyl by gavage on the above parameters, tissue vanadium accumulation in the gavaged rats was similar to that reported for rats given vanadium by drinking water. The present results (taken together with previous data) show that the administration of vanadium by gavage is not a viable alternative to the use of insulin in diabetes treatment.

Animals↗

Lack of effectiveness of several chelators in removing internally deposited strontium from mice following repeated parenteral strontium administration.

Diethylenetriaminepentaacetic acid (DTPA), ethylenglycolbis-(beta-amino-ethylether)-N,N-tetraacetic acid (EGTA), tartaric acid, KRYPTOFIX 222, and KRYPTOFIX 5 were evaluated for their efficacy in mobilization of strontium from the body of mice which had received 20 sc injections of strontium nitrate (95 mg/kg/injection) for 4 w. Twenty-four hours after the last strontium injection, ip administration of 1 of the various chelators or 0.9% saline was initiated and continued daily for 5 d. Mice were housed in metabolic cages, and urine and feces were collected daily for 5 d. After this period, the animals were killed and tissues removed. Tartaric acid, KRYPTOFIX 222, and KRYPTOFIX 5 had no effect on urinary or fecal strontium elimination, whereas DTPA and EGTA significantly decreased the fecal strontium excretion. The concentration of strontium in bone was only lowered in tartaric-treated mice. This study indicates the use of the above chelators is not an effective treatment to enhance the removal of strontium following repeated parenteral strontium administration.

Animals↗

Lead in children's hair, as related to exposure in Tarragona Province, Spain.

Concentrations of lead were determined in the hair of 478 school children living in an industrial and an agricultural area of Tarragona Province, Spain. The influence of age, sex, hair colour and family occupation on the children's hair lead concentration was also evaluated. Girls had more lead in their hair than boys (10.54 vs 6.55 micrograms g-1), and the lead levels decreased with age. Lead concentrations in hair with respect to hair colour decreased in the order red, blond, brown, black. Family occupation was one of the most significant factors influencing the lead content of children's hair. Although the average lead content was higher in the industrial area (9.38 micrograms g-1) than in the agricultural area (7.80 micrograms g-1), this difference was not statistically significant.

Adolescent↗

Oral vanadium administration to streptozotocin-diabetic rats has marked negative side-effects which are independent of the form of vanadium used.

In the present investigation, the effects of oral administration of sodium metavanadate, sodium orthovanadate and vanadyl sulphate to alleviate some signs of diabetes in streptozotocin-treated rats have been evaluated. Streptozotocin-induced diabetic rats drank aqueous solutions (NaCl, 80 mM) containing sodium metavanadate (0.15 mg/ml), sodium orthovanadate (0.23 mg/ml), or vanadyl sulphate pentahydrate (0.31 mg/ml) for 28 days. The vanadium-treated animals were compared to controls, either diabetic or nondiabetic, receiving drinking water containing NaCl (80 mM) only. Daily food and fluid intake were significantly decreased in the vanadium-treated animals relative to diabetic controls. Also, vanadium treatment reduced the level of hyperglycemia in diabetic rats, with sodium metavanadate being the most effective of the vanadium compounds tested. However, daily vanadium intake was significantly lower in the animals receiving sodium metavanadate. Signs of toxicity were observed in all vanadium-treated animals as evidenced by some deaths, decreased weight gain, and increased serum concentrations of urea and creatinine. Moreover, vanadium was detected in all tissues analyzed. Although some signs of diabetes were improved by vanadium treatment, because of the severe toxic side effects noted in all of the vanadium-treated animals, it seems evident that oral vanadium administration is not a suitable therapy of diabetes mellitus in streptozotocin-diabetic rats.

Administration, Oral↗

Effectiveness of some chelating agents on distribution and excretion of vanadium in rats after prolonged oral administration.

Vanadium has been shown to have a number of insulin-like effects and has been demonstrated to be beneficial in the treatment of streptozotocin-diabetic rats when included in the drinking water. However, some signs of toxicity and vanadium accumulation in all analysed tissues were reported in vanadium-treated animals. In the present study, the effect of repeated intraperitoneal administration of sodium 4,5-dihydroxybenzene-1,3-disulfonate (Tiron), ascorbic acid and deferoxamine mesylate (DFOA) or 2-mercaptosuccinic acid on the distribution and excretion of vanadium was determined in male Sprague-Dawley rats. Rats received sodium metavanadate (NaVO3) or vanadyl sulphate pentahydrate (VOSO4.5H2O) in the drinking water at concentrations of 0.15 mg ml-1 (NaVO3) and 0.31 mg ml-1 (VOSO4.5H2O) for 6 weeks. After the end of this exposure period, chelating agents were administered for 2 weeks (3 days per week) at doses approximately equal to one-tenth of their respective LD50. Urine was collected on days 1, 7 and 14 of treatment. Twenty-four hours after the final chelator injection, rats were killed and vanadium concentrations were determined in various tissues. Tiron and DFOA were effective compounds in mobilizing vanadium after NaVO3 administration, whereas Tiron was the most effective chelator after vanadyl sulphate administration. Ascorbic acid neither increased urinary elimination nor decreased tissue vanadium concentrations.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

Transport of organochlorine residues in the rat and human blood.

Organochlorine residues (OCR)2 are poorly soluble in water and are transported in the organism bound by the blood components. The distribution among blood fractions (cells/plasma, lipoproteins/rest of plasma proteins) were variable depending on the residue (HCB, p p'-DDE, HCH, Aroclor 1260, PCP) and on the species (rat, man). Differences were not found between in vivo (after oral single dosing) and in vitro (blood incubation) experiments. Results indicated a high affinity of organochlorine residues for lipoproteins; however, binding to blood carriers was very weak as demonstrated by the rapid release of residues by elution through a reverse phase column. The effects of residue binding to blood components on the distribution kinetics to tissues are discussed.

Administration, Oral↗

Evaluation of the effects of chelation therapy with time following strontium exposure to mice.

The effect of increasing the time interval between strontium exposure and chelation therapy was studied in male Swiss mice. Diethylenetriaminepentaacetic acid (DTPA), ethyleneglycol-bis-(beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA), 4,7,13,16,21,24-hexaoxa-1,10-diazabycyclo[8.8.8]-hexacosane (Kryptofix 222), tartaric acid, and 1,13-bis(8-chinolyl)-1,4,7,10,13-pentaoxatridecan (Kryptofix 5) were administered intraperitoneally at 0, 6, 12, and 24 h after subcutaneous injection of 1,139 mg/kg of strontium nitrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of strontium into urine and feces was determined for five days after which time the animals were killed, and the concentration of strontium was determined in various tissues. Only Kryptofix 222 was capable of increasing the total urinary elimination of strontium when given immediately after strontium exposure, whereas the amount of total strontium excreted into the feces was significantly enhanced by treatment with EGTA at 0 or 24 h after strontium injection, or with Kryptofix 222 at 6 h after strontium exposure. However, Kryptofix 222, tartaric acid, and Kryptofix 5 reduced the concentration of strontium in bone at 0, 6, or 12 h after strontium injection, whereas at 24 h only Kryptofix 5 significantly lowered the concentration of the metal in bone. The results of this study indicate that the length of time before initiating chelation therapy for strontium removal may influence remarkably the effectiveness of this therapy.

Animals↗

Cadmium in hair of school children living in Tarragona Province, Spain. Relationship to age, sex, and environmental factors.

Cadmium concentrations were determined in the hair of 226 school children in an industrial and in a rural area of Tarragona Province (NE Spain). The influence of sex, age, hair color, smoking habits of the household members, and parents' occupation on the children's hair cadmium levels was also evaluated. Children living in the industrial area had much more cadmium in their hair than those living in the rural area (median: 0.327 vs 0.002; arithmetic mean: 0.401 vs 0.119 micrograms/g). Girls had more cadmium in their hair than boys, and cadmium levels decreased with the age independently of the sex. Smoking habits and parents' occupation also influenced the hair cadmium content in the children examined. In contrast, hair color has no influence on hair cadmium values.

Adolescent↗

Developmental toxicity evaluation of orthovanadate in the mouse.

Sodium orthovanadate in deionized water was administered once daily by gavage on gestational days 6-15 to mice at doses of 0, 7.5, 15, 30, and 60 mg/kg. Dams were killed on day 18 of pregnancy, and fetuses were examined for external, visceral, and skeletal defects. Maternal toxicity was observed at the highest doses of sodium orthovanadate, as evidenced by a significant number of deaths (60 and 30 mg/kg/d) and reduced weight gain and food consumption (30 and 15 mg/kg/d). Embryolethality and teratogenicity were not observed at maternally toxic doses and below, but fetal toxicity was evidenced by a significant delay in the ossification process of some skeletal districts at 30 mg/kg/d. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 7.5 mg/kg/d, and 15 mg/kg/d represented a NOAEL for developmental toxicity in mice under the conditions of this study.

Animals↗

Studies on sex differences in excretion of sulphur derivatives of hexachlorobenzene and pentachloronitrobenzene by rats.

The appearance of sex-related differences in the excretion of sulphur derivatives of hexachlorobenzene (HCB) and pentachloronitrobenzene (PCNB) was studied in vitro and in vivo. Sexually immature rats given HCB showed initially no differences in the excretion of N-acetyl-S-(pentachlorophenyl)cysteine, but 5-8 days after weaning the urinary levels of the sulphur derivative began to increase in females until a 10-fold difference between both sexes was established. The studies in vitro and the analysis of tissues after in vivo administration of PCNB showed that conjugation with glutathione and hydrolysis of the conjugates to yield free pentachlorothiophenol do not present sex-related differences. These data tend to reinforce the view that an active renal secretory mechanism probably induced by estrogens during sexual maturation is responsible for the highly efficient excretion of sulphur derivatives of HCB and PCNB by female rats.

Administration, Oral↗

Evaluation of the efficacy of various chelating agents on urinary excretion and tissue distribution of vanadium in rats.

The effect of repeated intraperitoneal administration of Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid), ascorbic acid, deferoxamine (DFOA) or 2-mercaptosuccinic acid on urinary excretion and tissue distribution of vanadium was assessed in rats which had previously received 12 intraperitoneal injections of sodium metavanadate (1.84 mg/kg per injection) or vanadyl sulphate trihydrate (6.35 mg/kg per injection) during a 4-week period. Chelating agents were administered daily for 5 days at doses equal to one-eighth of their respective LDSO. Only Tiron significantly decreased the tissue concentration of vanadium, whereas DFOA and Tiron significantly enhanced the urinary excretion of vanadium after repeated parenteral administration of sodium metavanadate. Again, only Tiron significantly increased the urinary elimination of vanadium following vanadyl sulphate administration. The results of this study show that Tiron has potential beneficial effects in the treatment of repeated intraperitoneal vanadium poisoning, while the effectiveness of DFOA is very uncertain. 2-Mercaptosuccinic and ascorbic acids were not effective as antidotes for parenteral vanadium intoxication.

Animals↗

Influence of some dietary constituents on aluminum absorption and retention in rats.

Eight groups of female Sprague-Dawley rats were treated with 281 mg Al(OH)3/kg/day by gastric intubation five times a week for five weeks. Concurrently, animals in seven groups received ascorbic acid (56.3 mg/kg/day), citric acid (62 mg/kg/day), gluconic acid (62.7 mg/kg/day), lactic acid (28.8 mg/kg/day), malic acid (42.9 mg/kg/day), oxalic acid (28.8 mg/kg/day), and tartaric acid (48 mg/kg/day) in the drinking water. The eighth group did not receive any dietary constituent in the water and was designated as the control group. Animals were placed in plastic metabolic cages and urine was collected during the treatment period. The liver, spleen, kidney, brain and bone aluminum levels of each rat were measured, as well as the total amount of aluminum excreted into urine. All the dietary constituents significantly increased the aluminum concentrations in most of the tissues, with ascorbic and citric acids showing the highest rate of aluminum accumulation. In contrast, no significant differences between control and treated rats were observed in the concentrations of aluminum excreted into urine. In view of these results, we suggest that the effects of the simultaneous ingestion of aluminum hydroxide and those dietary constituents in uremic animals should be evaluated. Meanwhile, the diet of uremic patients should be carefully monitored.

Acids↗

Improvement of glucose homeostasis by oral vanadyl or vanadate treatment in diabetic rats is accompanied by negative side effects.

Vanadate and vanadyl, two forms of vanadium, have been reported to exert insulin-like effects in vivo and in vitro. In the present study we compared the effectiveness of oral sodium metavanadate (NaVO3), sodium orthovanadate (Na3VO4) and vanadyl sulphate pentahydrate (VOSO4.5H2O) treatment in alleviating some signs of diabetes in streptozotocin-induced diabetic rats. Vanadium compounds were administered in aqueous solutions of NaCl (80 mM) at concentrations of 0.20 mg/ml (NaVO3), 0.50 mg/ml (Na3VO4), and 1.1 mg/ml (VOSO4.5H2O) for two weeks. Control rats, either diabetic or non-diabetic, drank solutions of NaCl (80 mM). Although some signs of diabetes (hyperglycaemia, hyperphagia, polydipsia) were significantly ameliorated by the vanadium treatment, negative side effects were also observed in all of the vanadium-treated diabetic rats. Those effects included some deaths, decreased weight gain, and tissue vanadium accumulation, which are consistent with the reported toxicity of vanadium in non-diabetic rats. Vanadyl sulphate was the most effective compound of those tested in normalizing blood glucose levels. However, the results here reported suggest that chronic administration of vanadyl or vanadate in the drinking water is not a viable alternative treatment to insulin in human diabetes.

Administration, Oral↗