Search PubMed⌕ Search

Biomedical subjects

J Corbella

Publications and source records attributed to J Corbella.

At least 127 records · Page 7Linked to original sources
PubMed1991

Developmental toxicity evaluation of tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate) in mice.

Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate), a chelating agent used in the treatment of experimental metal poisoning, was evaluated for developmental toxicity in pregnant Swiss mice. Tiron was administered intraperitoneally on gestational days 6 through 15 at doses of 0, 750, 1500, or 3000 mg/kg/day. Cesarean sections were performed on gestation day 18. All fetuses were examined for external, visceral, and skeletal malformations and variations. Treatment with Tiron resulted in maternal toxicity at 3000 mg/kg/day as evidenced by a high number of deaths, reduced body weight during gestation and increased relative liver and kidney weights. There were no significant differences between treated and control animals on the number of total implants, dead fetuses, or sex ratio. However, embryo fetotoxicity was evidenced at 3000 mg/kg/day by a significant increase in the number of resorptions per litter, and a significant decrease in the average fetal body weight. There were no significant changes in the incidence of abnormalities (expressed as total, individual, external, visceral, or skeletal). The no observable adverse effect level (NOAEL) for maternal and developmental toxicity was 1500 mg Tiron/kg/day.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1991

The effects of repeated administration of various chelating agents on the removal of strontium from the mouse.

The effects of repeated ip administration of diethylenetriaminepentaacetic acid (DTPA), Kryptofix 222, 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6), ethylenglycol-bis-(beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA), and Kryptofix 5 on the distribution and excretion of sc-injected strontium were investigated in male Swiss mice. Groups of 20 animals received 95 mg strontium nitrate/kg, and 10 min later ip treatment with one of the chelators or 0.9% saline was initiated and continued for 10 d. The animals were housed in plastic metabolism cages, and urine and feces were collected daily during the period of treatment. At the end of this period, the animals were killed and the concentration of strontium determined in their tissues. Only Kryptofix 5 and EGTA significantly increased the amount of strontium excreted into feces, whereas none of the chelators significantly enhanced the urinary elimination of strontium. Treatment with Kryptofix 5 significantly decreased the concentration of strontium in all tissues analyzed. Kryptofix 5 was the most effective agent of those tested in the removal of strontium after a single dose of strontium nitrate.

Animals↗
PubMed1991

Effect of chelating agents on tissue distribution and excretion of strontium following semichronic strontium ingestion.

The effects of repeated ip administration of diethylenetriamine-pentaacetic acid (DTPA), ethylenglycol-bis-(-amino-ethlylether)-N,N'-tetraacetic acid (EGTA), Kryptofix 222, tartaric acid, and Kryptofix 5 on strontium (Sr) excretion and Sr levels in selected mouse tissues were investigated following semichronic strontium nitrate ingestion (284 mg/kg/day) for four weeks. Chelating agents were injected daily for five days at 1/4 of their respective LD50 in two equally divided doses. Only Kryptofix 5 significantly increased the amount of Sr excreted into urine, whereas none of the chelators enhanced the fecal Sr elimination. A significant decrease in the concentration of Sr in bone, the primary tissue of Sr deposition, was observed after treatment with EGTA. Under these experimental conditions, none of the chelators tested was able to remove significant amounts of Sr following Sr ingestion for four weeks.

Animals↗
PubMed1990

Chelating agents in the treatment of acute vanadyl sulphate intoxication in mice.

Eighteen chelating or reducing agents were tested to determine their relative efficacy as antagonists in acute intramuscular vanadyl sulphate intoxication in mice. The chelating or reducing agents were administered intraperitoneally to male Swiss mice at doses equal to one-fourth of their respective LD50. Therapeutic effectiveness (TEF) was calculated. In a subsequent experiment, the effect of EDTA, glutathione, DFOA, ascorbic acid, succinic acid, monosodium phosphate, Tiron, DTPA, and 2-mercaptosuccinic acid on the excretion, and distribution of vanadium was determined. Of the compounds examined, Tiron followed by ascorbic acid, and 2-mercaptosuccinic acid were effective in increasing the urinary excretion of vanadium. Tiron, and 2-mercaptosuccinic acid were also effective in reducing the concentration of vanadium found in kidney, the main target organ of vanadium accumulation. Tiron appears to be the most effective agent of those tested in the prevention of acute vanadium (IV) intoxication in mice.

Animals↗
PubMed1990

Developmental toxicity of vanadium in mice after oral administration.

Vanadium, as vanadyl sulphate pentahydrate, was evaluated for its embryotoxic, fetotoxic and teratogenic potential in Swiss mice. The compound was administered by gavage to pregnant mice at doses of 0, 37.5, 75 or 150 mg kg-1 day-1 on days 6-15 of pregnancy. On gestation day 18, all live fetuses were examined for external, visceral and skeletal malformations and variations. Maternal toxicity was observed in the vanadium-treated animals, as evidenced by reduced weight gain, reduced body weight on gestation day 18 (corrected for gravid uterine weight) and decreased absolute liver and kidney weights at 75 and 150 mg kg-1 day-1. The number of total implants, live and dead fetuses, late resorptions, the sex ratio and the post-implantation losses were not significantly different between the vanadium-treated mice and the controls. However, there was a significant increase in the number of early resorptions per litter at all dose levels. Fetotoxicity was evidenced by lower fetal weights and fetal lengths, and the presence of developmental variations. Malformation incidence also was increased by the administration of vanadium. Thus, the 'no observable effect level' (NOEL) for maternal toxicity, embryofetotoxicity and teratogenicity for vanadyl sulphate pentahydrate under these test conditions was below 37.5 mg kg-1 day-1 for Swiss mice.

Abnormalities, Drug-Induced↗
PubMed1990

Effects of oral meso-2,3-dimercaptosuccinic acid (DMSA) administration on late gestation and postnatal development in the mouse.

The present study was conducted to evaluate the effects of meso-2,3-dimercaptosuccinic acid (DMSA) on late gestation and postnatal viability and growth in the mouse. DMSA was given po to four groups of pregnant Swiss mice at 0, 200, 400, and 800 mg/kg/day from day 14 of pregnancy until postnatal day 21. At birth, the following data were recorded: length of gestation, number of live, dead, and abnormal pups, sex, and individual pup weights. Each pup was weighed again on day 4, 14, and 21 of lactation. Pinna detachment, incisor eruption and eye opening were also monitored. No treatment-related signs of toxicity were noted in any of the dams during the study. No adverse effects on offspring survival or development were evident in the 200 or 400 mg DMSA/kg/day groups. However, on days 14 and 21 of lactation a significant decrease in pup body weight was observed in the 800 mg/kg/day group. Also, a significant increase in the relative weight of the brain was seen in this group. The "no observable effect level" (NOEL) for health hazards to the developing pup was greater than 400 mg/kg/day. This dose is higher than the amounts of DMSA usually given in the treatment of human heavy metal intoxications.

Administration, Oral↗
PubMed1990

Evaluation of the developmental effects on mice after prenatal, or pre- and postnatal exposure to 2,3-dimercaptopropane-1-sulfonic acid (DMPS).

The sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS), a water soluble metal complexing agent, was administered to four groups of pregnant Swiss mice at 0, 70, 210, and 630 mg/kg/day by two dosing schedules: gestation day 14 until birth (prenatal exposure), and gestation day 14 until postnatal day 21 (pre- and postnatal section). Dams were allowed to deliver and the number of live and dead pups recorded. Each pup was sexed and weighed on days 0, 4, 14, and 21. Also, pinna detachment, incisor eruption and eye opening were monitored. No adverse effects on offspring survival or development were evident in either exposures at doses employed in this study. The "no observable effect level" (NOEL) for health hazard to the developing fetus or pup was 630 mg DMPS/kg/day. This dose is much higher than the amounts of DMPS usually administered in human heavy metal poisoning.

Animals↗
PubMed1990

Effectiveness of chelation therapy with time after acute uranium intoxication.

The effect of increasing the time interval between acute uranium exposure and chelation therapy was studied in male Swiss mice. Gallic acid, 4,5-dihydroxy-1,3- benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) were administered ip at 0, 0.25, 1, 4, and 24 hr after sc injection of 10 mg/kg of uranyl acetate dihydrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of uranium into urine and feces was determined for 4 days after which time the mice were killed, and the concentration of uranium was measured in kidney, spleen, and bone. The excretion of uranium was especially rapid in the first 24 hr. Treatment with Tiron or gallic acid at 0, 0.25, or 1 hr after uranium exposure significantly increased the total excretion of the metal. In kidney and bone, only administration of Tiron at 0, 0.25, or 1 hr after uranium injection, or gallic acid at 1 hr after uranium exposure significantly reduced tissue uranium concentrations. Treatment at later times (4 to 24 hr) did not increase the total excretion of the metal and did not decrease the tissue uranium concentrations 4 days after uranyl acetate administration. The results show that the length of time before initiating chelation therapy for acute uranium intoxication greatly influences the effectiveness of this therapy.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1990

Evaluation of the developmental toxicity of 2,3-dimercapto-1-propanesulfonate (DMPS) in mice. Effect on mineral metabolism.

The sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS), a potent chelating agent used in the treatment of inorganic and organic heavy metal intoxications was evaluated for developmental toxicity in pregnant Swiss mice. DMPS was administered by gavage at doses of 0, 75, 150 and 300 mg/kg per day on gestational days 6-15. Females were evaluated for body weight gain, food consumption, appearance and behavior, survival rates and reproduction data. Cesarean sections were performed on gestation day 18. There were no maternal toxic effects, and no treatment-related changes were recorded in the number of total implants, resorption, the number of live and dead fetuses, fetal body weight or fetal sex distribution data. Gross external, soft tissue and skeletal examination of the DMPS-treated fetuses did not show significant differences at any dose in comparison with the controls. Mineral analysis of maternal and fetal tissues revealed slight effects of DMPS on metabolism of calcium, magnesium, zinc, copper and iron. The results of this study in mice indicate that DMPS is not a developmental toxicant at levels up to 300 mg/kg per day.

Abnormalities, Drug-Induced↗
PubMed1990

Oral meso-2,3-dimercaptosuccinic acid in pregnant Sprague-Dawley rats: teratogenicity and alterations in mineral metabolism. I. Teratological evaluation.

meso-2,3-Dimercaptosuccinic acid (DMSA), an effective antagonist for the treatment of lead, arsenic, mercury, and cadmium poisoning, was evaluated for developmental toxicity in pregnant Sprague-Dawley rats. DMSA was administered by gavage on d 6-15 of gestation at doses of 0, 100, 300, or 1000 mg DMSA/kg/d. At termination on d 20 of gestation, fetuses were examined for external, visceral, and skeletal malformations and variations. Maternal toxicity was observed at all doses, as evidenced by a significant decrease in body weight gain. There were no effects with respect to hematology or clinical chemistry. Increased early resorptions, increased percentage postimplantation loss, and reduced fetal body weight per litter were observed at 100, 300, and 1000 mg/kg/d. Examination of fetuses for gross external abnormalities, visceral and skeletal malformations, or ossification variations revealed that DMSA did not produce teratogenicity at any dosage level. However, significant fetotoxicity was observed at 100, 300, and 1000 mg/kg/d. The no-observable-effect level (NOEL) for maternal and developmental toxicity was less than 100 mg DMSA/kg/d.

Administration, Oral↗
PubMed1990

Oral meso-2,3-dimercaptosuccinic acid in pregnant Sprague-Dawley rats: teratogenicity and alterations in mineral metabolism. II. Effect on mineral metabolism.

The effect of meso-2,3-dimercaptosuccinic acid (DMSA) on mineral metabolism was investigated in pregnant Sprague-Dawley rats. Animals were given by gavage doses of 0, 100, 300, or 1000 mg DMSA/kg/d on gestational d 6-15. On d 20 of gestation dams were killed and fetuses were removed from the uterus. The levels of calcium, magnesium, zinc, copper, and iron were measured in maternal liver, kidney, and intestine, as well as in whole fetus and in fetal liver. Mineral analysis of maternal and fetal tissues revealed pronounced effects of DMSA on mineral metabolism. The results of this investigation indicate a strong possibility that the negative effects of the drug on pregnancy are due in part to the changes in mineral metabolism.

Administration, Oral↗
PubMed1990

Fatal poisoning by Rumex crispus (curled dock): pathological findings and application of scanning electron microscopy.

A case of fatal poisoning due to ingestion of the plant Rumex crispus (curled dock) is described. The patient, a 53-year-old male, presented with gastrointestinal symptoms, severe hypocalcemia, metabolic acidosis and acute hepatic insufficiency. Despite therapeutic measures, the patient died 72 h after ingestion of the plant material. Noteworthy among the pathological findings were centrolobular hepatic necrosis and birefringent crystals in the liver and kidneys that were identified by histochemical techniques and scanning electron microscopy. These observations are compared with other reports in the medical literature, with an emphasis on the risk involved in the use of these plants for culinary or medicinal purposes.

Edema↗
PubMed1990

Evaluation of the maternal and developmental toxicity of aluminum from high doses of aluminum hydroxide in rats.

The potential of aluminum hydroxide [Al (OH)3] to induce developmental toxicity in rats was evaluated in the present study. Al (OH)3 was given by gavage at dose levels of 192, 384, and 768 mg/kg/day to groups of pregnant rats from day 6 through day 15 of gestation. Control animals received distilled water. Pregnant rats were evaluated for body weight, weight gain, food consumption, appearance, behavior and reproduction data. Cesarean sections were performed on gestation day 20, and the fetuses were removed for teratological evaluation. No significant maternal or developmental toxicity was observed at any Al (OH)3 dose level. Consequently, the no-observed-effect level (NOEL) for Al(OH)3 maternal or developmental toxicity would be greater than or equal to 768 mg/kg/day, which was the highest dose tested. This dose would be equivalent to a 60 kg person ingesting 16 g Al/day.

Aluminum Hydroxide↗
PubMed1989

Fatal mushroom poisoning in Barcelona, 1986-1988.

In 1986-88, 46 poisonings (4 of which were fatal) caused by amatoxin mushroom were reported. The fatalities were males aged between 7 and 65 years. They all had gastrointestinal symptoms and three of the patients died of acute hepatic insufficiency. The fourth died as a result of an intestinal perforation. The clinical and pathological alterations are compared with the findings of other authors.

Adolescent↗