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Biomedical subjects

J Corbella

Publications and source records attributed to J Corbella.

At least 181 records · Page 10Linked to original sources

Nutritional and toxicological effects of short-term ingestion of aluminum by the rat.

Aluminum nitrate was given orally to four groups of female Sprague-Dawley rats over a period of one-hundred days at doses of 0, 360, 720 and 3600 mg/kg/day. Rats were monitored for weight gain, food intake, drinking water, hematology and plasma chemistry. The results show that the ingestion of aluminum nitrate by the rat caused a significant decrease in its growth. The nutritional parameters were always significantly lower for the treated animals. Aluminum did not accumulate dose-dependently in the organs and tissues analysed. Histopathological studies, including organ weight determinations, did not show significant changes. The possibility of oral aluminum intoxication in the human would be very low.

Aluminum↗

Embryotoxic effects of sodium metavanadate administered to rats during organogenesis.

Pregnant Sprague-Dawley rats were given orally a daily dose of 0, 5, 10 or 20 mg NaVO3/kg from the sixth through the fourteenth day of pregnancy. Fetal examinations were performed on day 20 of gestation. Sodium metavanadate was neither embryolethal nor teratogenic in rats when administered orally at 20 mg/kg/day or lower. Nevertheless, this dose was embryotoxic.

Animals↗

Effects of oral aluminum administration on perinatal and postnatal development in rats.

Aluminum nitrate was administered by gavage to four groups of pregnant Sprague-Dawley rats from the 14th day of gestation through 21 days of lactation at doses of 0, 180, 360 and 720 mg/kg/day. These doses did not produce overt fetotoxic effects. However, the growth of the offspring was significantly less from birth and during all the period of lactation for the higher doses of aluminum nitrate. Although very few toxic effects could be observed for the 180 mg/kg/day group (or 13 mg Al/kg/day), this quantity is similar to the amounts ingested by some people in special medical treatment (10 mg Al/kg/day). Therefore, it would seem that high amounts of aluminum should not be ingested during the periods of gestation.

Aluminum↗

Effects of vanadium on reproduction, gestation, parturition and lactation in rats upon oral administration.

Sodium metavanadate was tested for its effects on fetal development, reproduction, gestation and lactation in Sprague Dawley rats. Male rats were administered NaVO3 po at doses of 0, 5, 10 and 20 mg/kg/day for sixty days before mating with females which had received the same doses from 14 days previous to mating. These females received 0, 5, 10 and 20 mg NaVO3/kg/day during the periods of gestation and lactation. No significant adverse effects could be observed on: number of corpora lutea, implantations, live and dead fetuses, and resorptions. Significant decreases were observed in the development of the pups in all the vanadium -treated groups. All the doses used produced toxic effects in the offspring.

Administration, Oral↗

Influence of chelating agents on the toxicity, distribution and excretion of vanadium in mice.

The effects of the chelating agents Na2Ca-ethylendiaminetetraacetate (EDTA), Na3Ca-diethylentriaminepentaacetate (DTPA), L-cysteine, 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron) and deferoxamine mesylate and the reducing agent ascorbic acid on the toxicity, excretion and distribution of i.p. injected vanadium were studied in male Swiss mice. Chelating and reducing agents were administered intraperitoneally at doses equal to one-fourth of their respective LD50. To determine the effects of the various chelators on the mortality of vanadium, various doses of NaVO3 (0.30-1.20 mmol kg-1 i.p.) were given, followed immediately by one of the chelating or reducing agents. Survival was recorded at the end of 14 days. Significant increases in survival were noted with ascorbic acid, Tiron and deferoxamine, with ascorbic acid being the most effective. Deferoxamine and Tiron were the most effective in increasing the excretion of vanadium and reducing the concentration of vanadium found in various tissues. However, ascorbic acid appears to be the most effective agent in the prevention of vanadium intoxication.

Animals↗

Comparison of the effectiveness of several chelators after single administration on the toxicity, excretion and distribution of cobalt.

The effects of the chelating agents Na2Ca-ethylendiaminetetraacetate (EDTA), Na3Ca-diethylentriaminepentaacetate (DTPA), L-cysteine, 2,3-dimercaptosuccinic acid (DMSA), N-acetyl-L-cysteine (NAC), glutathione, D,L-penicillamine (D,L-PEN) and 2,3-dimercaptopropanol (BAL) on the toxicity, distribution and excretion of intraperitoneally injected cobalt were studied in male Swiss mice. To determine the effect of the various chelators on the toxicity of cobalt, various doses of CoCl2 (0.60-1.80 mmol/kg) were given, followed immediately by the IP administration of the chelator (at a dose equal to one-fourth of their respective LD50). EDTA and DTPA were the most effective. EDTA, DTPA and L-cysteine, NAC and glutathione were also the most effective in increasing the urinary excretion of cobalt and reducing the concentration of the metal in various tissues. EDTA appears to be the most effective agent of those tested in the prevention of acute cobalt intoxication.

Acetylcysteine↗

Mobilization, redistribution and excretion of hexachlorobenzene following food restriction in rats.

Adult female rats were given a single oral dose of hexachlorobenzene (HCB) (100 mg/kg, 1% carboxy methyl cellulose) by stomach tube. Six days after HCB dosage the diet of the animals was restricted to 30% of their normal intakes for 7 days. Following dosage and during partial starvation faecal elimination of HCB was monitored. The animals were killed on day 13 and their tissues removed for HCB analysis. A significant increase in HCB was found in all tissues, notably in the brain (367%) and the liver (496%), with HCB being mobilized from fat depots to plasma and then redistributed. The pattern of HCB faecal elimination suggests that food restriction enhances non-biliary excretion, correlating with plasma levels and faecal volume.

Animals↗

Acute aluminium intoxication: a study of the efficacy of several antidotal treatments in mice.

The effect of the chelating agents deferoxamine mesylate (DFOA), sodium salicylate, citric acid, Na2Ca-ethylendiaminetetracetate (EDTA), nitrilotriacetic acid (NTA), L-cysteine, N-acetyl-L-cysteine (NAC) and 2, 3-dimercaptosuccinic acid (DMSA) on the lethality, elimination and tissue retention of aluminum was investigated on male Swiss mice. To determine the effect of the various chelators on the lethality of aluminium, various doses of Al (NO3)3.9H2O (3.0 - 7.5 mmol/kg) were given intraperitoneally followed immediately by the ip administration of the chelator (at dose equal to one-third of their respective LD50). Survival was recorded at the end of 14 days. Significant increases in survival were noted with citric acid and DFOA. A decrease of the aluminium concentration in various tissues, and an increase in urinary and fecal elimination of aluminium were also noted with citric acid, DFOA, and sodium salicylate. Citric acid appear to be the most effective agent of those tested in the prevention of acute aluminum intoxication.

Aluminum↗

Short-term toxicity studies of vanadium in rats.

Vanadium (in the form of NaVO3) was given in drinking water to groups of 10 male Sprague-Dawley rats over a period of 3 months at concentrations of 0, 5, 10 and 50 ppm. Vanadium accumulated dose-dependently in the kidneys and spleen. Appearance, behaviour, food and water consumption, growth and mortality of the treated rats of all groups were not affected during the 3-month period. Histopathological investigation showed only mild though dose-dependent lesions in kidneys and spleen. The plasma concentrations of urea and uric acid were increased in the highest exposure groups.

Animals↗

Protection of mice against the lethal effects of sodium metavanadate: a quantitative comparison of a number of chelating agents.

10 Chelating agents were administered to mice by intraperitoneal (i.p.) injection in order to compare their relative effectiveness in preventing death after a single i.p. injection of NaVO3. Ascorbic acid, Tiron (4,5-dihydroxy-1,3-benzene-disulfonic acid) and deferoxamine were the most effective antidotes for acute NaVO3-toxicity. The therapeutic index of ascorbic acid against 0.61 mmol/kg NaVO3 was found to be 95.2. This was 4.6 and 12.2 times greater than those of Tiron and Deferoxamine respectively. L-Cysteine greater than Na2CaEDTA greater than Na3CaDTPA reduced the acute mortality of mice following i.p. injection of NaVO3. Sodium salicylate, D,L-penicillamine, DMSA and DDC were not effective as antidotes for acute NaVO3-toxicity.

Animals↗

Effects of cobalt on postnatal development and late gestation in rats upon oral administration.

Four groups of pregnant Wistar rats, each of which consisted of 15 animals were administered 0, 12, 14 and 48 mg/kg/day of cobalt (II) chloride from the 14th day of gestation through 21 days of lactation. The offspring were observed for mortality, body weight, body and tail length and general symptomatology after 1, 4 and 21 days of nursing. The number of litters was higher for the control group. The survival ratios were also higher for the control group. Besides, a dose-dependent delay in the growth of the living young could be observed. No significant differences in organ weights in the animals killed 21 days after birth were observed. The blood parameters analysed did not show differences between the treated and control pups. Cobalt produced toxic effects on the mothers, affecting the late gestation as well as the postnatal development of the pups.

Animals↗

Comparison of antidotal efficacy of chelating agents upon acute toxicity of Co(II) in mice.

The relative efficacy of 14 chelating agents in alleviating acute cobalt (II) chloride (ip) intoxication has been determined. For a level of 0.70 mmol/kg ip of CoCl2 (slightly higher than its LD50), the ip administration of chelating agents at a 2:1 and 5:1 mole ratio resulted in a significant antidotal action for L-cysteine, N-acetyl-cysteine, L-histidine,glutathione,D,L-penicillamine, DMSA, DTPA and EDTA. For a level of 1.18 mmol/kg ip of CoCl2 (slightly higher than its LD99) only L-cysteine, N-acetylcysteine,glutathione, DMSA, DTPA and EDTA resulted in a significant enhancement of the survival rate. The therapeutic indices of these compounds were respectively: 8.3, 11.8, 10.9, 9.1, 20.5 and 26.4; with EDTA and DTPA being the most effective. However, due to their low toxicity, N-acetylcysteine and glutathione should be considered as possible alternatives.

Animals↗

The effects of EDTA in acute cobalt intoxication in rats.

The effect of EDTA on acute cobalt toxicity in rats was the subject of our investigation. There was complete effectiveness for two methods of treatment of the Co and EDTA, except when the CoCl2 was given orally and EDTA intraperitoneally. When the CoCl2-EDTA complex was given orally or intraperitoneally there were no deaths, not even at LD100 values of the CoCl2. No noteworthy changes were brought about in the hematological parameters and serum parameters of the animals receiving the CoCl2-EDTA complexes after a week's treatment. Significant differences appeared in the variation of some blood parameters measured 12 hours after the administration of the Co/CH3-COO)2-EDTA complex compared with the same parameters measured on giving only Co(CH3-COO)2.

Administration, Oral↗

Acute thallium poisoning: an evaluation of different forms of treatment.

Hemodialysis, forced potassium diuresis, chelating agents per os, and Dithiocarb given intravenously during short periods of time were used for the treatment of acute thallium poisoning (ingestion of 750 mg of thallium sulfate), and the effectiveness of these different therapeutic procedures was analyzed. Chelating agents per os (Prussian blue, Dithiocarb, and Dithiozone) were ineffective in our patient, since fecal excretion of thallium was very low and unmodified by them. Forced potassium diuresis and hemodialysis were very useful therapeutic measures, especially in the first 12 days following ingestion. Dithiocarb perfusion seems to be the most effective method for enhancing urinary thallium excretion. This method might be most useful in the treatment of thallium poisoning if its deleterious effects could be eliminated.

Acute Disease↗

Relative efficacy of chelating agents on excretion and tissue distribution of manganese in mice.

The effect of repeated parenteral administration of a number of structurally diverse chelating agents on the excretion and tissue distribution of manganese was assessed in mice following 4 weeks of manganese exposure. Males Swiss mice received s.c. injections of manganese(II) chloride tetrahydrate (8.9 mg Mn kg-1 body wt.) for 4 weeks (5 days per week). After the end of this exposure period, cyclohexanediaminetetraacetic acid (CDTA), ethyleneglycol-bis-(beta-aminoethylether)-N,N-tetraacetic acid (EGTA), N-(2-hydroxyethyl)ethylenediamine triacetic acid (HEDTA), isonicotinyl hydrazine (INH), L-dopa, sodium 4.5-dihydroxy-1.3-benzenedisulphonate (Tiron), p-aminosalicylic acid (PAS) or 0.9% saline (control group) were given i.p. for five consecutive days. The doses of the chelators were approximately equal to one-eighth of their respective LD50 values. Urine and faeces were daily collected for 5 days. Twenty-four hours after the final chelator injection, mice were killed and manganese concentrations were determined in various tissues. Although CDTA, EGTA and HEDTA significantly enhanced the elimination of manganese into urine, none of the chelators increased faecal excretion. Tissue concentrations of manganese were significantly reduced only by CDTA. According to these results, among the compounds tested only CDTA would mobilize effectively manganese in manganese-loaded mice.

Animals↗