Correlação entre a exposição ao chumbo e a atividade da enzima ácido d-aminolevulínico desidratase (ALA-D), paratormônio (PTH) e fatores nutricionais em crianças / Correlation between the exposition to the leads and the activity of the aminolevulinic acid enzyme dehydratase (ALA-D), (PTH) and nutritional factors in children

O percentual de recuperação da enzima Ácido d-Aminolevulínico Desidratase (ALA-D) é um indicador de efeito sensível e específico para toxicidade ao chumbo mesmo a baixos níveis de chumbo em sangue (Pb-S). Atualmente, a saúde das crianças expostas ambientalmente às substâncias tóxicas tem sido objeto de grande atenção. Muitos estudos têm encontrado uma associação inversa entre o Pb-S e o crescimento ósseo. A homeostasia do cálcio é regulada pela ação do paratormônio (PTH), da Vitamina D e da Calcitonina, podendo o chumbo afetar aspectos deste metabolismo. O objetivo deste estudo foi avaliar os efeitos do chumbo sobre o metabolismo ósseo em crianças de 0 a 16 anos através da determinação da ALA-D em sangue e correlacionar com os níveis de PTH e fatores nutricionais. Este estudo foi realizado na comunidade João Goulard, em Manguinhos, no Rio de Janeiro. As amostras biológicas foram coletadas no Laboratório do CSEGSF/ENSP, onde os questionários de freqüência alimentar e sócio-econômicos foram aplicados. A determinação da atividade enzimática da ALA-D e do PTH foram realizados por Espectrofotometria e quimioluminescência, respectivamente...

Inhibition of chlorophyll biosynthesis by mercury in excised etiolated maize leaf segments during greening: effect of 2-oxoglutarate.

Mercury (0.01-1.0 mM) inhibited chlorophyll formation in greening maize leaf segments. However, supplementing incubation medium with 2-oxoglutarate, maintained substantially higher level of chlorophyll in absence of metal after an initial period of 8 hr. On preincubation of leaf segments with HgCl2, per cent inhibition of chlorophyll synthesis by metal was same in the presence and absence of 2-oxoglutarate. Supply of 2-oxoglutarate (0.1-10.0 mM) exerted concentration dependent effect on chlorophyll formation in absence or presence of metal. Increase in delta-amino levulinic acid dehydratase as well as NADH-glutamate synthase activity and decrease in NADH-glutamate dehydrogenase activity by 2-oxoglutarate in the presence of Hg suggested that glutamate for delta-amino levulinic acid synthesis could be made available from NH4+ assimilation via., glutamine synthetase/glutamate synthase pathway during mercury toxicity.

Heavy metals alter photosynthetic pigment profiles as well as activities of chlorophyllase and 5-aminolevulinic acid dehydratase (ALAD) in Amaranthus lividus seedlings.

Varied concentrations of PbCl2 and CdCl2 in the germinating media reduced the total chlorophyll and carotenoid contents in primary leaves of Amaranthus lividus seedlings (168 h old). When chlorophyll a and chlorophyll b contents were measured separately, greater loss of chl b than chl a under the identical conditions of heavy metal treatment was observed In addition, the loss of total chlorophyll was more than carotenoids under the same magnitude of heavy metal treatment. The effect of heavy metal treatment at germination stage was further studied on chlorophyll accumulation in primary leaves in relation to the activities of 5-aminolevulinic acid dehydratase (ALAD) and chlorophyllase. The activities of ALAD gradually diminished in response to both the heavy metals in a concentration-guided manner, while the activities of chlorophyllase did not exhibit any significant change.

Effects of lead and/or zinc exposure during the second stage of rapid postnatal brain growth on delta-aminolevulinate dehydratase and negative geotaxis of suckling rats

Lead has been shown to produce cognitive and motor deficits in young rats that could be mediated, at least in part, by inhibition of the zinc-containing heme biosynthetic enzyme delta-aminolevulinate dehydratase (ALA-D). In the present study we investigated the effects of lead and/or zinc treatment during the second stage of rapid postnatal brain development on brain, kidney and blood ALA-D specific activity, as well as the negative geotaxis behavior of rats. Eight-day-old Wistar rats were injected intraperitoneally with saline, lead acetate (8 mg/kg) and/or zinc chloride (2 mg/kg) daily for five consecutive days. Twenty-four hours after treatment, ALA-D activity was determined in the absence and presence of DL-dithiothreitol (DTT). The negative geotaxis behavior was assessed in 9- to 13-day-old rats. Treatment with lead and/or zinc did not affect body, brain or kidney weights or brain- or kidney-to-body weight ratios of the animals. In spite of the absence of effect of any treatment on ALA-D specific activity in brain, kidney and blood, the reactivation index with DTT was higher in the groups treated with lead or lead + zinc than in the control group, in brain, kidney and blood (mean + or - SEM; brain: 33.33 + or - 4.34, 38.90 + or - 8.24, 13.67 + or - 3.41; kidney: 33.50 + or - 2.97, 37.60 + or - 2.67, 15.80 + or - 2.66; blood: 63.95 + or - 3.73, 56.43 + or - 5.93, 31.07 + or - 4.61, respectively, N = 9-11). The negative geotaxis response behavior was not affected by lead and/or zinc treatment. The results indicate that lead and/or zinc treatment during the second stage of rapid postnatal brain growth affected ALA-D, but zinc was not sufficient to protect the enzyme from the effects of lead in brain, kidney and blood.

Effects of aluminum sulfate on delta-aminolevulinate dehydratase from kidney, brain, and liver of adult mice

The purpose of the present study was to investigate the in vitro and in vivo effects of aluminum sulfate on delta-aminolevulinic acid dehydratase (ALA-D) activity from the brain, liver and kidney of adult mice (Swiss albine). In vitro experiments showed that the aluminum sulfate concentration needed to inhibit the enzyme activity was 1.0-5.0 mM (N = 3) in brain, 4.0-5.0 mM (N = 3) in liver and 0.0-5.0 mM (N = 3) in kidney. The in vivo experiments were performed on three groups for one month: 1) control animals (N = 8); 2) animals treated with 1 g per cent (34 mM) sodium citrate (N = 8) and 3) animals treated with 1 g per cent (34 mM) sodium citrate plus 3.3 g per cent (49.5 mM) aluminum sulfate (N = 8). Exposure to aluminum sulfate in drinking water inhibited ALA-D activity in kidney (23.3 + ou - 3.7 per cent, mean + ou - SEM, P<0.05 compared to control), but enhanced it in liver (31.2 + ou - 15.0 per cent, mean + ou - SEM, P<0.05). The concentrations of aluminum in the brain, liver and kidney of adult mice were determined by graphite furnace atomic absorption spectrometry. The aluminum concentrations increased significantly in the liver (527 + ou - 3.9 per cent, mean + ou - SEM, P<0.05) and kidney (283 + ou - 1.7 per cent, mean + ou - SEM, P<0.05) but did not change in the brain of aluminum-exposed mice. One of the most important and striking observations was the increase in hepatic aluminum concentration in the mice treated only with 1 g per cent sodium citrate (34 mM) (217 + ou - 1.5 per cent, mean + ou - SEM, P<0.05 compared to control). These results show that aluminum interferes with delta-aminolevulinate dehydratase activity in vitro and in vivo. The accumulation of this element was in the order: liver > kidney > brain. Furthermore, aluminum had only inhibitory properties in vitro, while in vivo it inhibited or stimulated the enzyme depending on the organ studied.

Delta-aminolevulinic acid dehydratase (ALAD) activity in blood of Bufo arenarum (Anura)

The aim of the present investigation was to standardize a method for measuring delta-aminolevulinic acid dehydratase (ALAD) activity in circulating red blood cells of adult Bufo arenarum kept in controlled environmental conditions, and to obtain reference basal values suitable for environmental monitoring of lead exposure. The normal ALAD activity for B. arenarum was 131.86 + 14.47 U per liter of red blood cells (n = 38, mean + SEM; interval 72.98 - 263.33). In animals exposed to lead, ALAD activity decreased as lead dose increased.

Alteraciones en el camino metabólico del hemo en pacientes diabéticos / Changes in the heme metabolic pathway in diabetic patients

In the last decades several authors have observed a frequent association between diabetes mellitus and porphyria, mainly porphyria cutanea tarda. In previous studies, it has been demonstrated that both d delta d-aminolevulic acid dehydratase (ALA-D) and porphobilinogen deaminase (PBG-D), enzymes of the heme pathway, are inhibited by high concentrations of glucose in vitro in crude preparations of erythrocytes. The activity of these same enzymes was diminished in different tissues obtained from streptozotocin induced diabetic mice. Therefore, we decided to investigate the incidence of heme metabolism alterations in diabetes mellitus in a population of 100 non selected adult patients. The activities of erythrocytic ALA-D and PBG-D were measured. Rhodanese, an enzyme of the sulfocompounds pathway closely related to the regulation of heme biosynthesis, was also studied. Urine porphyrin content as well as the chromatographic pattern of esterified porphyrins were determined. ALA-D and PBG-D activities were diminished in diabetic patients (40 and 20 respectively), while rhodanese was only slightly increased (Fig. 1). ALA-D activity was subnormal in a 92 of the complete diabetic population, while PBG-D activity was less than normal in a 79 of the same population. No significative differences between enzymic activities were observed in the groups insulin and non-insulin dependent (Fig. 3). Urine porphyrin content was increased in 5 of the diabetic population. Chromatographic pattern of urinary porphyrins was notably altered in diabetic patients irrespectively of their porphyrin content (Fig. 4), suggesting an alteration in the enzyme uroporphyrinogen decarboxylase resembling the primary enzymic defect observed in porphyria cutanea tarda.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of methylmercury exposure during the second stage of rapid postnatal brain growth on negative geotaxis and on delta-aminolevulinate dehydratase of suckling rats

In the present study, we examined the effects of exposure to methylmercury (0, 2.3, 4.6, 6.9 and 9.2 mg/kg, daily for 5 consecutive days, sc) during the second stage of rapid postnatal brain development (8 to 12 days of age) on the sulfhydryl-containing enzyme delta-aminolevulinate dehydratase (ALA-D, E.C. 4.2.1.24) from brain, liver and kidney and on motor performance (latency to complete a negative geotaxis response) of rats. ALA-D specific activity of 13-day old rats of both sexes (7-12 per group) was reduced significantly in rats treated with 6.9 mg/kg and 9.2 mg/kg in brain (about 40 per cent , P < 0.05) and in liver (about 25 per cent , P < 0.05). Renal ALA-D specific activity was not affected by methylmercury treatment. The in vitro IC50 for inhibition of brain, liver and renal ALA-D was 79.3, 81.8 and 39.1 microM, respectively. The latency to complete the negative geotaxis response of 12-day old rats was increased by 6.9 (7.9 +/- 0.7 s, mean +/- SEM) and 9.2 mg/kg methylmercury (7.8 +/- 0.5 s) when compared with control rats (5.8 +/- 0.3 s), suggesting an impairment in motor performance of exposed rats. These results demonstrate that exposure to relatively high doses of methylmercury during the second stage of brain development causes a significant reduction in brain and hepatic ALA-D. The absence of inhibition of ALA-D by lower doses may be related to the relatively low in vitro sensitivity of the enzyme to methylmercury. The possible involvement of ALA-D inhibition on the neurotoxicity of methylmercury deserves additional investigation

Synergistic effect of allyl isopropyl acetamide with cadmium on hepatic heme synthesis in chick embryo.

The effect of cadmium along with a porphyrogenic drug, allyl isopropyl acetamide, on the induction of 5-amino levulinic acid (ALA) synthetase, ALA dehydratase and heme level was studied. The interaction of cadmium with allyl isopropyl acetamide indicated that the decrease in hepatic heme level by cadmium or allyl isopropyl acetamide may occur in a synergistic manner, whereas the induction of ALA synthetase by cadmium or allyl isopropyl acetamide may not take place in the same manner. Further, neither allyl isopropyl acetamide treatment alone nor allyl isopropyl acetamide-cadmium treatment had any effect on ALA dehydratase activity.

Alteraçöes na atividade enzimática da ácido delta-aminolevulínico desidratase (ALA-D) eritrocitária de ratos, provocadas pela ingestäo "ad libitum" de chumbo, zinco, cobre e cromo / Changes in the enzymatic activity of delta-aminol evulinic acid dehydratase in the rat erythrocyte induced by ingestion ad libitum of lead, zinc, copper and chromium

Foram verificadas as interferências do chumbo, zinco, cobre e cromo, sobre a atividade enzimática do ácido delta-aminolevulínico desidratase (ALA-D). Cinco grupos de oito ratos WISTAR, machos, pesando entre 180 e 200 gramas, receberam individualmente "ad libitum", soluçöes aquosas contendo 200 ppm de apenas um dos elementos químicos pesquisados, por sete semanas consecutivas. As porcentagens de inibiçäo da ALA-D determinados nos Grupos Expostos em relaçäo ao Grupo Controle foram, respectivamente, 14,5% para o Cr6+; 30,6% para o Cr3+; 30,6% para o Cu2+, 11,3% para Zn2+ e 62,9% para Pb2+