Comparison of the hepatotoxicity of toxin T-514 of Karwinskia humboldtiana and its diastereoisomer in primary liver cell cultures.

Toxin T-514 of Karwinskia humboldtiana has been demonstrated to be hepatotoxic in vivo and in vitro. Recently a diastereoisomer of T-514 has been isolated. In the present study we have evaluated and compared the in vitro hepatoxicity of the diastereoisomer of T-514 using primary cultures of rat hepatocytes. Cytotoxicity was evaluated by release of cytoplasmic enzyme lactate dehydrogenase (LDH), and mitochondrial metabolic function (MTT reduction). The diastereoisomer was shown to be almost as hepatoxic in vitro as toxin T-514.

Toxicity assessment of toxins T-514 and T-544 of buckthorn (Karwinskia humboldtiana) in primary skin and liver cell cultures.

The present study was undertaken to assess and compare the in vitro cytotoxicity of toxins T-514 and T-544 of buckthorn (Karwinskia humboldtiana) using primary cultures of rat hepatocytes and keratinocytes. Cell cultures were exposed to 6, 12, 25 and 50 microM toxins for 2-, 4-, 6- and 24-h periods. Cytotoxicity was determined by release of the cytoplasmic enzyme, lactate dehydrogenase (LDH), in culture media, methylthiazoltetrazolium (MTT) reduction and neutral red (NR) uptake. An increase in LDH leakage was observed in liver cell cultures as early as 2 h with 50 microM T-544 and with 6 microM T-514 and T-544 at 6 h and 24 h, respectively. In the NR assay the toxicity was evident at 2 h with 12 microM T-514 and T-544 and with 6 microM concentrations of both toxins at 6 h. On the other hand, a decrease in MTT reduction was detected at 4 h with 50 microM concentrations of both toxins and with 25 microM T-544 and 12 microM T-514 at 6 h and 6 microM T-514 and T-544 at 24 h. Both toxins were shown to be highly hepatotoxic; T-514 was more toxic than T-544. In the skin cell cultures, the toxicity of the toxins was not as severe and was not expressed until 12 h of exposure.

Toxicity assessment of toxins T-514 and T-544 of buckthorn (Karwinskia humboldtiana) in primary skin and liver cell cultures.

The present study was undertaken to assess and compare the in vitro cytotoxicity of toxins T-514 and T-544 of Buckthorn (Karvinskia humboldtiana) using primary cultures of rat hepatocytes and keratinocytes. Cell cultures were exposed to 6, 12, 25 and 50 microM concentrations of the toxins for 2, 4, 6 and 24-h periods. Cytotoxicity was determined by release of the cytoplasmic enzyme, lactate dehydrogenase (LDH), in culture media, methylthiazoltetrazolium (MTT) reduction and neutral red (NR) uptake. An increase in LDH leakage was observed in liver cell cultures as early as 2 h with 50 microM T-544 and with 6 microM T-514 and T-544 at 6 h and 24 h, respectively. In the NR assay the toxicity was evident at 2 h with 12 microM T-514 and T-544 and with 6 microM concentrations of both toxins at 6 h. On the other hand, a decrease in MTT reduction was detected at 4 h with 50 microM concentrations of both toxins and with 25 microM T-544 and 12 microM T-514 at 6 h and 6 microM T-514 and T-544 at 24 h. Both toxins were shown to be highly hepatotoxic; T-514 was more toxic than T-544. In the skin cell cultures, the toxicity of the toxins was not as severe and was not expressed until 12 h of exposure.

Structural improvement of higher education in environmental toxicology in Latin America and Europe.

Industrial development has resulted in an increased release of chemicals and other agents into the environment, resulting in damage to the environment as well as increasing the risk of adverse effects on human health. Environmental toxicology (ET) is the discipline responsible for assessing the risks to human health and the environment from the effects of new chemicals and those already present in the environment. The development of human resources in toxicology is therefore a priority in both Latin America (LA) and the European Union (EU), although LA professionals are more involved in risk evaluation than in risk assessment compared to their EU colleagues. A solid background in general toxicology will enable those interested in environmental issues to tackle local problems. Moreover, the increasing globalization of markets and, therefore, of the necessary regulations, requires harmonisation of postgraduate programmes to ensure that risk assessment and management related to the environment are dealt with uniformly and by highly qualified scientists. The Inaugural Meeting of the ALFA-OMET Toxicology', a 2-year programme supported by the European Commission, offered the opportunity to discuss a number of these issues. The present status of existing ET courses in the EU and LA and the corresponding professional profiles in the two regions were examined, and a harmonized academic curriculum for a postgraduate professional profiles in the two regions were examined, and a harmonized academic curriculum for a postgraduate course in environmental toxicology was developed. Finally, a course programme for toxicology and a specialization in environmental toxicology designed by a panel of experts was discussed, and its relevance as a model for other specialisation programmes was analysed. Exercises such as those performed by ALFA-OMET may be useful not only in promoting discussion for the implementation of national and international professional registers in LA, but also in encouraging the same, ongoing process in the EU.

Production of reactive oxygen species by toxin T-514 of genus Karwinskia in vitro.

In the present study we have analyzed the production of reactive oxygen species by toxin T-514 of the genus Karwinskia in vitro (primary liver cell cultures and microsomes), as well as their possible role in its cytotoxicity. The role of catalase and superoxide dismutase (SOD) as defense mechanisms against oxidative stress was also studied. Freshly isolated hepatocytes or microsomes were exposed to T-514 in the presence or absence of catalase and SOD. Cytotoxicity was determined by methylthiazoltetrazolium (MTT) reduction. Oxidative stress was evaluated by the dichlorofluorescein diacetate (DCFDA) fluorescent probe and the reduction of ferricytochrome c. Exposure of hepatocytes to toxin T-514 for 2-, 4-, 6- and 24-h periods resulted in a time- and concentration-dependent increase in the suppression of mitochondrial metabolic activity. T-514 induced the production of reactive oxygen species in both hepatocytes and microsomes. Catalase and superoxide dismutase had a protective effect against the cytotoxicity of T-514 in hepatocytes and also inhibited the production of oxygen reactive species in microsomes. The results indicate that oxidative stress mediated by reactive intermediates may be a mechanism by which T-514 induces its cytotoxic effect.

Effect of meso-2,3-dimercaptosuccinic acid on urinary lead excretion in exposed men.

The efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) was evaluated in workers occupationally exposed to lead (Pb; blood level >50 microg/dL). Ten men were given 600 mg of DMSA per orem daily, for five days. Pb concentrations of whole blood and urine were determined throughout therapy. Hematology analyses, blood chemistry, and urinalysis were obtained at the start of the study, at the end of the DMSA treatment, and at 72 hours after the administration of the final dose. DMSA therapy had no influence on hepatic, hematologic, or renal functions and was effective in decreasing the concentration of blood Pb in all the subjects without adverse drug reactions.

Evaluation of urinary mercury excretion after administration of 2,3-dimercapto-1-propane sulfonic acid to occupationally exposed men.

The purpose of this study was to determine the clinical efficacy of 2,3-dimercapto-1-propane sulfonic acid, Na salt, on the urinary excretion of mercury as well as its possible adverse effects. Ten men with occupational mercury exposure (urinary level of 50 micrograms/g creatinine or more) were assigned to receive 2,3-dimercapto-1-propane sulfonic acid p.o. (DIMAVAL capsules, 100 mg) 300 mg/d for five days. Informed written consent was obtained from each subject. Hematology analyses, blood, chemistry, and urinalysis were obtained at the start of the study, at the end of the 2,3-dimercapto-1-propane sulfonic acid treatment and 72 hours after the administration of the final dose of 2,3-dimercapto-1-propane sulfonic acid. Twenty-four-hour urine mercury levels were closely monitored throughout therapy. All data and measurements before and during drug doses were evaluated by analyses of variance. In all subjects mean urine mercury was significantly increased (p < .05) after pre-2,3-dimercapto-1-propane sulfonic acid treatment. One subject had a moderate hypersensitivity reaction (rash) to 2,3-dimercapto-1-propane sulfonic acid but no other toxic effects were observed.

Intravenous self-administration of metallic mercury: report of a case with a 5-year follow-up.

CASE REPORT: A case of intravenous self-administration of elementary mercury is presented. The increase urinary excretion of mercury after treatment with 2,3-dimercaptopropane-1-sulfonate is reported on a 5-year follow-up. No biochemical abnormalities in hepatic or renal function nor clinical pulmonary malfunction have been detected, despite the persistence of metallic densities in the body. The only persistent symptoms are tremor and lower extremity weakness. Any long term benefits of 2,3-dimercaptopropane-1-sulfonate treatment remains to be determined.

Urinary mercury in twelve cases of cutaneous mercurous chloride (calomel) exposure: effect of sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) therapy.

OBJECTIVE: To evaluate clinical symptoms and urinary mercury before and after chelation therapy in subjects with chronic cutaneous mercurous chloride (HgCl; calomel) exposure. SUBJECTS: Twelve women from 19-45 years who had used a facial cream which contained HgCl (5.9%) for 2 to 10 years. DESIGN: Twenty-four hour urine samples were collected for basal urine mercury. All the subjects received a 5-day cycle of oral sodium 2,3 dimercaptopropane-l-sulfonate (Dimaval capsules 100 mg) 200 mg/d on an outpatient basis. The urine mercury excretion was monitored 24 hours after the first dose and 72 hours after the last dose in eight subjects. RESULT: Exanthem and tremor were detected in two of 12 subjects. The range of urine mercury was 180 to 1876 micrograms/g creatinine. A significant increase in the urinary mercury excretion was observed in the first 24 hours after beginning sodium 2,3-dimercaptopropane-1-sulfonate. CONCLUSION: Chronic topical application of 5.9% HgCl cream was associated with clinical mercurialism in two subjects and with high urinary mercury level in all the cases. Sodium 2,3-dimercaptopropane-1-sulfonate was effective in increasing urine mercury.

Urinary excretion of trace elements in humans after sodium 2,3-dimercaptopropane-1-sulfonate challenge test.

OBJECTIVE: To evaluate the effects of intravenous sodium 2,3-dimercaptopropane-1-sulfonate (DMPS, Dimaval) on urinary excretion of essential trace elements in subjects who received this chelating agent as a mercury challenge test. SUBJECTS: Eleven subjects sought medical attention due to concern with the toxicity of mercury released from dental amalgam fillings. DESIGN: The subjects were given DMPS 3 mg/kg intravenously. Spot urine samples were collected 1 hour before and 1 hour after the DMPS dose for laboratory analysis. In addition to mercury, the urinary excretion of copper, zinc, selenium, magnesium, manganese, molybdenum, chromium, cobalt, and aluminum were measured. RESULTS: A significant increase in urinary excretion of mercury (3- to 107-fold) was observed after the DMPS dose. The DMPS treatment led to a 2- to 119-fold increase in copper excretion; 3- to 43.8-fold in selenium excretion; 1.6- to 44-fold in zinc excretion; and 1.75- to 42.7-fold in magnesium excretion. The excretion of manganese, chromium, cobalt, aluminium, and molybdenum remained unchanged. CONCLUSIONS: In this study, an intravenous DMPS challenge test produced a significant increase in mercury excretion and also led to an increased excretion of copper, selenium, zinc, and magnesium.

Blood acetaldehyde levels in alcohol-dosed rats after treatment with ANIT, ANTU, dithiocarbamate derivatives, or cyanamide.

In adult female Wistar rats, pretreated by gavage with two doses - 16 or 256 mumol/kg - of cyanamide, TMTD (tetramethylthiuram disulfide), TMTM (tetramethylthiuram monosulfide), Ziram or Zineb at 90 min or 18 h before administration of 2 g of ethanol/kg i.p., the blood acetaldehyde levels were significantly increased for 90 - 240 min after ethanol administration (exceptions were noted after exposure to Zineb for 90 min or to low-dosed cyanamide for 18 h). After pretreatment for identical periods with ANTU (N-1-naphthylthiourea) or ANIT (1-naphthylisothiocyanate) at doses extending into the LD50 range, the blood acetaldehyde levels of rats given the same dose of ethanol remained uninfluenced. The increase in blood acetaldehyde recorded after 16 mumol/kg p.o. of TMTM and TMTD remained detectable for up to 48 h. Onset of the cyanamide action occurred already after 45 min. While recognizing that results from animal experiments cannot be transposed without restriction to the human situation, it is concluded that occupational contacts with ANTU or ANIT are not likely to elicit increased blood acetaldehyde levels in man after ingestion of alcohol. The risk of an ethanol intolerance reaction due to a rise in blood acetaldehyde therefore does not appear to be warranted. The present findings indicate, however, that exposure to TMTD, TMTM, Ziram, Zineb or cyanamide is associated with a definite health risk; because of the long persistence of these substances in the body, the risk exists for a long time post-exposure.

Intoxicaciones: un estudio retrospectivo en el Hospital Universitario Dr. José E. González, 1980 - 1984 / Intoxications: a retrospective study at the \"Dr. José E González\" University Hospital 1980 - 1984

Se efectuó un estudio retrospectivo de las intoxicaciones registradas en el Hospital Universitario "Dr. José E. González" (H.U.) de 1980 a 1984 en el cual se consideraron los siguientes puntos: edad y sexo del paciente, tipo y modo de intoxicación, mortalidad y total de intoxicaciones en este periodo. El ingreso total de pacientes al H.U. fue de 182,247 del cual el 0.26% (477) correspondió a intoxicaciones siendo las más frecuentes: petróleo (Kerosene), cáusticos, salicilatos, alcohol etílico y atropina. El modo de intoxicación fue accidental en un 90% de los casos e intento de suicidio en 10%. La mayoría fueron niños (70%) y un 30% adultos; 277 masculinos y 200 femeninos. La mortalidad por intoxicaciones fue de 1.25% (6 de 477 pacientes) y las substancias relacionadas con estas muertes fueron digitálicos (3), salicilatos (1), talio (1) y cáusticos (1)