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Biomedical subjects

F X Reichl

Publications and source records attributed to F X Reichl.

30 records · Page 2Linked to original sources
PubMed1992

Effect of various antidotes on biliary excretion of arsenic in isolated perfused livers of guinea pigs after acute experimental poisoning with As2O3.

The effect of the dithiols British Anti-Kewisite (BAL), dimercaptopropanesulfonic acid (DMPS), dimercaptosuccinic acid (DMSA) and a new metal binding agent 2,3-bis-(acetylthio)- propanesulfonamide (BAPSA) on the biliary excretion of arsenic in perfused livers of guinea pigs after acute experimental poisoning with As2O3 was investigated. Guinea pigs received As2O3, 10.0 mg/kg subcutaneously at 9 a.m. as a single injection. One hour after the injection the livers were perfused (2.5 ml x min.-1 x g-1 liver) with Krebs-Henseleit buffer and glucose for 80 min. After 40 min. of saline perfusion (control) 0.1 or 0.7 mmol/l BAL, DMSA, DMPS, or BAPSA were added to the perfusate and arsenic elimination in the bile and effluent perfusate was measured. The biliary excretion of arsenic in control livers between 40 and 80 min. was 0.7% of the total arsenic liver content before perfusion (= arsenic liver content after perfusion + portion excreted in the bile+perfusate). After antidote addition (0.1 mmol/l) the excretion was 0.2% for livers perfused with BAL, 6.8% for DMSA, 10.6% for DMPS, and 11.1% for BAPSA, respectively. After 0.7 mmol/l antidote the excretion of arsenic was 0.1% in livers perfused with BAL, 9.6% for DMSA, 12.3% for DMPS, and 13.3% for BAPSA, respectively. Except BAL, all compounds and most effectively BAPSA increased biliary excretion of arsenic. This indicates that excretion of arsenic which normally is mainly renal is shifted towards faecal excretion by the dithiols.

Animals↗
PubMed1991

Pyruvate and lactate metabolism in livers of guinea pigs perfused with chelating agents after repeated treatment with As2O3.

The relative effectiveness of British Anti-Lewisite (BAL), dimercaptopropanesulfonic acid (DMPS), dimercaptosuccinic acid (DMSA), and a new metal binding agent 2,3-bis(acetylthio)propanesulfonamide (BAPSA) was compared by determining their effect on pyruvate metabolism in perfused livers of guinea pigs after repeated treatment with As2O3. Guinea pigs received As2O3, 2.5 mg/kg s.c. twice daily on 5 consecutive days (total dose 25 mg/kg). Sixteen hours after the last dose the livers were perfused (2.5 ml/min/g liver) with Krebs-Henseleit buffer and glucose (10 mmol/l) as substrate for 80 min. After 50 min of perfusion 0.1 or 0.7 mmol/l BAL, DMPS, DMSA, or BAPSA were added to the perfusate for 30 min. Samples of the effluent were collected every 10 min; lactate and pyruvate were determined enzymatically. As compared to controls, a significant decrease in the pyruvate and lactate efflux was observed in perfused livers of guinea pigs treated with As2O3. After influx of BAL (0.1 mmol/l), DMSA (0.7 mmol/l), and BAPSA (0.1 and 0.7 mmol/l) respectively, the pyruvate and lactate efflux and the oxygen consumption (exception BAL 0.1 mmol/l) increased and reached control values without arsenic treatment. On the other hand, the pyruvate and lactate efflux and the oxygen consumption was further significantly decreased after influx of 0.7 mmol/l BAL.

Animals↗
PubMed1991

Effect of glucose treatment on carbohydrate content in various organs in mice after acute As2O3 poisoning.

Glucose treatment improved survival and symptoms in mice poisoned with As2O3. In order to get more insight into the mechanisms involved, postmortum changes in glucose and glycogen content of various organs and pathology were investigated in mice acutely poisoned with As2O3 and treated with glucose. Forty mice each received 12.9 mg As2O3/kg sc as a single injection. The first group of 10 mice had no further treatment. Fifteen minutes after the As2O3 injection and every 2 h thereafter, the second group (10 mice) received saline and the third group (10 mice) received 5% glucose ip. Groups 4 and 5 (5 mice each) received either saline or glucose only. The injection volume in all groups was 10 microliters/g mouse. Group 6 (5 mice) had no treatment whatsoever. Immediately after death brain, muscle and kidneys were prepared for the enzymatic determination of glucose and glycogen. Samples of the brain, muscle, kidneys, liver, small intestine, colon and spleen were taken for microscopic examination. Independent of the therapeutic procedure, decreases in the glycogen in livers and increases in fat in livers and muscles were observed in mice which died. All mice which died showed heavy leucocytes disruptions, increased fat, and decreased glycogen in the spleen. Intrafolliculary disruptions of leucocytes in the small intestine and colon, as well as patchy hyperemias and hemorrhagic spots in the papilla of the kidneys, were observed in non-survivor mice. Decreased glucose and glycogen was in the brains of non-survivor mice; no differences in glucose and glycogen were found in brains of the mice which survived.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1990

Effect of glucose in mice after acute experimental poisoning with arsenic trioxide (As2O3).

Carbohydrate depletion (glucose and glycogen) was reported to be a major problem in acute arsenic poisoning. In the present paper the effectiveness of glucose substitution was investigated in mice after acute experimental poisoning with As2O3. Four groups of ten mice each received As2O3, 12.9 mg/kg, s.c. After the injection the first group remained without further treatment, the second received saline every 2 h, the third 5% glucose, and the fourth 5% glucose +0.12 IE insulin/kg i.p. Groups 5 and 6, five mice each, received either saline or glucose only. Group 7, five mice, remained without any treatment. Immediately after death the livers were removed for the enzymatic determination of glucose and glycogen. Mice receiving As2O3 only died within 22 h. The mean survival time was 12.4 h. In mice receiving As2O3 and after that saline, glucose, or glucose + insulin, an increase in the survival time to 30.8, 40.7, and 43.6 h, respectively, was observed. All mice which died showed a significant decrease in the liver glucose and glycogen content, compared to control animals. In livers of survivors, the glucose and glycogen content was not different to the control groups. The data support the assumption that carbohydrate depletion is an important factor in arsenic toxicity, and its substitution should be considered in the treatment of arsenic poisoning.

Animals↗
PubMed1990

Efficacy of various dithiol compounds in acute As2O3 poisoning in mice.

The efficacy of DL-dimercaptopropanol (British Anti-Lewisite, BAL), DL-dimercaptopropanesulfonate (DMPS), and meso-dimercaptosuccinic acid (DMSA) was compared in reducing the acute As2O3 toxicity in mice. Mice were treated with a single equimolar dose of a dithiol compound (0.7 mmol/kg i.p.) 0.5 or 30 min after the s.c. injection of various doses of As2O3. Both DMPS and DMSA were significantly (p less than or equal to 0.05) more effective in mice treated 0.5 min after the poisoning if compared to BAL on an equimolar level. The highest potency ratio (PR) (LD50 with treatment/LD50 without treatment) was found in animals injected with DMSA (PR = 8.6). The corresponding value for DMPS was 4.2, and for BAL 2.1, respectively. In animals treated 30 min after poisoning the efficacy of DMPS (PR = 2.6) was similar to the efficacy of DMSA 2.4, both being only slightly superior to BAL 2.0. DMPS and DMSA were found to be much less toxic than BAL. The LD50 of arsenic was 0.057 mmol/kg. The efficacy of BAL, DMPS, and DMSA in reducing the tissue content of arsenic following acute As2O3 poisoning was investigated in mice (n = 6/group) and guinea pigs (n = 3-4/group). The animals were injected s.c. with 0.043 mmol/kg As2O3 (containing a tracer dose of 74As(III)). Thirty minutes later the antidotes were administered i.p. (0.7 mmol/kg). From 2 to 4 h after As2O3 poisoning bile was collected from guinea pigs. Four h after As2O3 injection the content of 74As in blood, liver, kidneys, spleen, heart, lungs, brain, testes, skeletal muscle, and skin in mice and guinea pigs was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of chelating agents on biliary excretion of arsenic in perfused livers of guinea pigs pretreated with As2O3.

The effect of the dithiols British Anti-Lewisite (Bal), dimercapto-propanesulfonic acid (DMPS), dimercaptosuccinic acid (DMSA) and a new metal binding agent 2,3-bis-(acetylthio)-propanesulfonamide (BAPSA) on the biliary excretion of arsenic in perfused livers of guinea pigs pretreated with As2O3 was investigated. Guinea pigs received As2O3, 2.5 mg/kg sc twice daily for 5 consecutive days. Sixteen hours after the last dose the livers were perfused (35 ml/min) with Krebs-Henseleit buffer with glucose for 80 min. After 50 min of perfusion 0.1 mmol/L or 0.7 mmol/L BAL, DMSA, DMPS, or BAPSA were added to the perfusate and arsenic elimination in the bile and effusate was measured. The total arsenic excretion in control livers between the 50th and 80th min was 6.1% of the total arsenic liver content. After antidote addition (0.1 mmol/L) the excretion increased to 7.9% (DMSA), 9.2% (BAL), 23.9% (BAPSA), and 27.1% (DMPS), respectively. After 0.7 mmol/L of antidote the excretion of arsenic was found to be 19.3% (DMSA), 19.9% (DMSA), 24.0% (BAL), and 43.3% (BAPSA), respectively. The increase resulted mainly from increased biliary excretion. In these experiments BAPSA was significantly more effective in the overall elimination of arsenic than DMSA, DMPS, and BAL. The treatment with chelating agents may cause a substantial shift to fecal elimination by the increase in biliary excretion (BAL less than DMSA less than DMPS less than BAPSA). From the therapeutic view the shift to fecal elimination may have the advantage that the amount of the toxicant which passes the kidney is reduced and thereby also the portion which might be harmful for the organ.

Animals↗
PubMed1989

Effects on mitochondrial metabolism in livers of guinea pigs after a single or repeated injection of As2O3.

Differences in the metabolite pattern were observed in previous experiments in guinea pig livers after a single injection or prolonged (5 days) treatment with AS2O3 (Reichl et al. 1988). To elucidate the underlying mechanism the effect of As2O3 on liver metabolism was therefore investigated. Male guinea pigs received either a single dose (s.d.) of As2O3 10 mg x kg-1 s.c. or repeated doses (r.d.) of 2.5 mg x kg-1b.i.d. on 5 consecutive days. One hour after the s.d. or 1 h and 16 h after the last injection in the r.d. groups the animals were sacrificed in anaesthesia. The livers were removed by freeze clamping for the determination of various metabolites. In the s.d. group a significant decrease in hydroxybutyrate, acetylCoA, adenosinemonophosphate and in the ratio of hydroxybutyrate/acetoacetate and an increase in pyruvate, citrate, malate, and adenosinetriphosphate were observed. A significant decrease in glycogen, pyruvate, alpha-ketoglutarate, acetylCoA, and acetoacetate and a significant increase in malate and in the ratios of lactate/pyruvate and hydroxybutyrate/acetoacetate were observed in the r.d.1-h group. In the r.d.16-h group a significant decrease in glycogen, pyruvate, lactate, and adenosinemonophosphate was found, but the values tended towards control values. The data are consistent with mechanisms of As2O3 toxicity in other species as PDH inhibition with consecutive citric acid cycle and gluconeogenesis inhibition and excessive carbohydrate depletion.

Animals↗
PubMed1989

Lack of effectiveness of D-penicillamine in experimental arsenic poisoning.

Based on some anecdotal case reports D-penicillamine (DPA) has been advocated for the treatment of arsenic poisoning. Experimental evidence, however, supporting that recommendation is lacking. In the present experiments the effectiveness of DPA was compared with dimercaprol (British Antilewisite, BAL), dimercaptopropanesulfonate (DMPS), and dimercaptosuccinic acid (DMSA) using different controlled experimental settings. In one study mice received As2O3 (9-14 mg/kg sc). Treatment with DMSA after 30 min afforded almost complete protection against the lethal effects of arsenic whereas DPA was not effective. In a second study, mice and guinea pigs were injected sc with 8.4 mg/kg As2O3 (containing a tracer dose of 74As). Thirty min later 0.7 mmol/kg of DPA or one of the other antidotes was injected ip. As determined 4 and 12 h after the arsenic injection, DPA was unable to reduce the 74As content in any of the organs investigated (blood, liver, kidneys, lungs, heart, brain, testes, spleen, skeletal muscle, and skin). On the other hand, BAL, DMPS, and DMSA markedly reduced the tissue content of 74As with respect to controls. Finally, the ability of the antidotes to reverse biochemical effects of arsenic was investigated in vitro using suspensions of incubated renal tubulus cells. The marked inhibition of gluconeogenesis induced by 30 mumol/L As2O3 was almost completely reversed upon addition of 90 mumol of either BAL, DMPS, or DMSA. In this experimental model, too, DPA was ineffective. It was concluded that the use of DPA in arsenic poisoning needs to be reevaluated.

Animals↗
PubMed1988

Effect of arsenic on carbohydrate metabolism after single or repeated injection in guinea pigs.

Divergent pattern in pyruvate efflux from livers perfused with As2O3 and livers of animals previously repeatedly treated with the toxicant was observed in earlier experiments (Reichl et al. 1987, 1988). Further studies of the effect of As2O3 on carbohydrate metabolism were therefore performed. Male guinea pigs received either a single dose of As2O3 10 mg.kg-1 s.c. or repeated doses of 2.5 mg.kg-1 bis in die (b.i.d.) on 5 consecutive days. One hour after the single dose or 1 h and 16 h after the last injection in the repeated treatment group the animals were sacrificed under anaesthesia. The livers were removed by a freeze-stop technique and the contents of glycogen and glycolysis intermediates were measured. In the single dose group a decrease in fructose-1,6-diphosphate and glycerol-aldehyde-3-phosphate and an increase in phosphoenol-pyruvate and pyruvate was observed. In the repeat dose, 1-h group a significant decrease in glycogen, glucose-6-phosphate, fructose-6-phosphate, glycerolaldehyde-3-phosphate, dihydroxyacetonephosphate, 2-phosphoglycerate and pyruvate was found. In the repeat dose, 16-h group the contents of glycogen, glucose-6-phosphate, pyruvate and lactate were diminished. The most prominent finding after repeated As2O3 administration was a marked depletion in total carbohydrate content. This was due mainly to depletion of glycogen.

Animals↗