Arsenic In Organs Research Articles

Male reproductive toxicity of sodium arsenite in mice.

The effect of chronic oral exposure to arsenic on male mouse testicular and accessory sex organ weights, sperm parameters and testicular marker enzymes was studied. In addition, the distribution of arsenic in reproductive organs was measured using atomic absorption spectrophotometry. Sodium arsenite administered to mice (Mus musculus) via drinking water at a dose of 53.39 micromol/L (4 ppm As) for 365 days caused a decrease in the absolute and relative testicular weight. However, epididymal and accessory sex organ weight was similar to control. The activities of marker testicular enzymes such as sorbitol dehydrogenase, acid phosphatase and 17beta-hydroxy-steroid dehydrogenase (17beta-HSD) were significantly decreased, but those of lactate dehydrogenase and gamma-glutamyl transpeptidase (gamma-GT) were significantly increased. A decrease in sperm count and sperm motility, along with an increase in abnormal sperm, was observed in arsenite-exposed mice. A significant accumulation of arsenic in testes, epididymis, seminal vesicle and prostate gland was observed in treated animals. Thus long term exposure (365 days) at the dose level of 53.39 micromol/L sodium arsenite (4 ppm As), to which human beings are likely to be exposed via drinking water, may cause testicular and spermatotoxic effect.

Intratumoral injection of arsenic to enhance antitumor efficacy in human esophageal carcinoma cell xenografts

To enhance the therapeutic efficacy of anticancer agents and to reduce systemic side effects, it was decided to study the effect of arsenic trioxide directly on solid tumors to observe the anticancer effect of arsenic on tumors and the distribution of arsenic in tumors and other organs. Esophageal carcinoma cells were heterotransplanted in severe combined immunodeficient (SCID) mice in both laterals of the abdominal wall. When both lateral tumors had grown to approximately 10x8x5 mm3, tumor-bearing mice were used for 2 experiments. The right tumors were treated with intratumoral injection of As2O3 in 1, 5 and 10 micro g per day for 10 days sequent. The left tumors were treated with phosphate buffer solution as controls. To explore the distribution of As2O3 remaining in tumor and some organs, a single intratumoral injection of As2O3 was studied with quantitative measurement of arsenic by means of atomic absorption spectrometry. The results revealed that on the 17th day after the 1st injection As2O3-treated tumors were suppressed markedly compared to that of the contrarily lateral tumor accompanied by marked apoptosis and necrosis in tumor cells. The tumor growth inhibition (TGI) was 13.56, 62.37 and 76.92% in 1, 5 and 10 micro g group, respectively. There were no pathological changes in heart, lung, spleen, liver, kidney or brain after arsenic administration. Distribution of As2O3 revealed that As2O3 remained at higher concentration in arsenic-treated tumor tissue than in other organs. Our data suggest that intratumoral delivery of As2O3 efficiently suppresses growth of transplanted esophageal carcinoma without systemic side effects. The protocol of As2O3 intratumoral injection will be its potential clinical utility for therapy of solid tumors.

Glutathione-conjugated arsenics in the potential hepato-enteric circulation in rats.

The metabolic pathways for arsenic were precisely studied by determining the metabolic balance and chemical species of arsenic to gain an insight into the mechanisms underlying the animal species difference in the metabolism and preferential accumulation of arsenic in red blood cells (RBCs) in rats. Male Wistar rats were injected intravenously with a single dose of arsenite (iAs(III)) at 2.0 mg of As/kg of body weight, and then the time-dependent changes in the concentrations of arsenic in organs and body fluids were determined. Furthermore, arsenic in the bile was analyzed on anion and cation exchange columns by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). The metabolic balance and speciation studies revealed that arsenic is potentially transferred to the hepato-enteric circulation through excretion from the liver in a form conjugated with glutathione (GSH). iAs(III) is methylated to mono (MMA)- and dimethylated (DMA) arsenics in the liver during circulation in the conjugated form [iAs(III)(GS)(3)], and a part of MMA is excreted into the bile in the forms of MMA(III) and MMA(V), the former being mostly in the conjugated form [CH(3)As(III)(GS)(2)], and the latter being in the nonconjugated free form. DMA(III) and DMA(V) were not detected in the bile. In the urine, arsenic was detected in the forms of iAs(III), arsenate, MMA(V), and DMA(V), iAs(III) being the major arsenic in the first 6-h-urine, and DMA(V) being increased in the second 6-h-urine. The present metabolic balance and speciation study suggests that iAs(III) is methylated in the liver during its hepato-enteric circulation through the formation of the GSH-cojugated form [iAs(III)(GS)(3)], and MMA(III) and MMA(V) are partly excreted into the bile, the former being in the conjugated form [CH(3)As(III)(GS)(2)]. DMA is not excreted into the bile but into the bloodstream, accumulating in RBCs, and then excreted into the urine mostly in the form of DMA(V) in rats.

Male reproductive effect of arsenic in mice.

Arsenic, a known human carcinogen, was given to mice via drinking water as sodium arsenite at a dose 53.39, 133.47, 266.95 and 533.90 micromol 1 for 35 days. A decrease in the activity of 17 beta HSD along with increase in LDH, gammaGT activity were observed at 533.90 micromol l. The observed sperm count, motility and morphological abnormalities in sperm were similar to control at lower dose levels. However at 533.90 micromol l a significant decrease in sperm count and motility along with increase in abnormal sperm were noticed. Significant accumulation of arsenic in testes and accessory sex organs may be attributed to the arsenic binding to the tissues or greater cellular uptake. No effects were observed on indices studied for reproductive effects at 53.39 micromol l arsenic close to which human being are exposed through drinking water under the present set of experimental conditions.

Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing toxic effects produced by arsenic trioxide in mice: I. On rate of accumulation of arsenic in certain vital organs

The widespread occurrence of arsenic poisoning in West Bengal, India led us to examine the extent of deposition of arsenic in different vital organs of mice after a single sublethal injection of arsenic trioxide and if microdoses of arsenic could reduce the deposition effectively in them. For each fixation interval, 15 mice were injected intramuscularly with As 2 O 3 in a single dose @ 1.0 mg/kg body weight and were divided into three batches and another batch of five mice injected with normal saline served as negative control (saline control). Among arsenic treated mice, one batch was fed with diluted potentized alcohol-30 (alcohol-treated-positive control), one batch with a potentized homoeopathic drug Arsenicum Album-30 in ultra low doses (active treatment) while the remaining one was neither fed with potentized alcohol nor with the potentized homoeopathic drug (as-intoxicated control). The accumulation of arsenic was determined by spectrophotometric analysis in four tissues, namely, liver, kidney, spleen and testis at seven different fixation intervals, viz. 12 hours, 24 hours, 48 hour, 7 days, 21 days, 30 days and 90 days. In arsenic treated mice orally administered with the homoeopathic drug, statistically significant decreases in accumulation were observed in all tissues at most fixation intervals as compared to controls. This homoeopathic drug can be considered to effectively antagonize and antidote arsenic poisoning. * Anisur R Khuda Bukhsh, Kalyani University, Department of Zoology, Kalyani 741235 W B, India

XRF analysis of arsenic uptaking in mice organs and tissues

In this work, an investigation on the levels of uptaken arsenic in different organs and tissues of mice was carried out. Mice were given water, doped with 100 μg/ml of As 2O 3, during a period of a week. The Energy Dispersive X-Ray Fluorescence (EDXRF) technique was used for the measurements; the external standard (calibration curve) and the internal standard (addition) methods were used to obtain concentrations. These methods were used in order to minimize matrix effects (which in many cases are complex and prone to errors) and to allow an easy calculation of As concentrations. The average concentrations obtained here were: 3.9 μg/g for liver, 13 μg/g for pre-stomach, 21 μg/g for esophagus, 2.9 μg/ml for blood, and 42 μg/ml for urine.

Effects of hijiki feeding on arsenic distribution in rats administered large doses of arsenate

AbstractMale rats fed a diet of 5% Hijiki seaweed or 5% cellulose for two weeks were administered large doses of sodium arsenate (Na2HAsO4) 7mg As kg−1 of body weight, during two days. At 48 h following the last arsenic administration, selected organs were isolated and homogenized. Femur and feces were lyophilized; portions of them were irradiated with thermal neutrons in a research nuclear reactor and their arsenic concentrations were determined from the induced gamma radiation from 76As. The greatest concentration of arsenic was detected in blood cells. A greater arsenic level was found in urine from the Hijiki diet group than in that of the cellulose diet group. The percentage distribution of arsenic in various organs indicated that the arsenic concentrated in blood cells 48 h after the arsenate administration, in comparison with the value 24 h after the arsenate administration [M. Katayama et al., Appl. Organomet. Chem. 6 389 (1992)]. The Hijiki diet accelerated arsenic accumulation in blood cells and the femur more than the cellulose diet, and arsenic levels in other organs (liver, heart, lung and kidney) of the Hijiki diet group decreased faster than those from the cellulose diet group.

Arsenic, cadmium, lead and mercury in meat, livers, and kidneys of swine slaughtered in The Netherlands during the period 1980-1985.

The results obtained between 1980 and 1985 in a Dutch monitoring programme on the presence of arsenic, cadmium, lead and mercury in meat and organs of swine are presented. For meat, livers and kidneys the median values were, respectively, 0.001, 0.001, and 0.003 mg/kg (fresh weight) for arsenic, 0.002, 0.044, and 0.260 mg/kg for cadmium, 0.01, 0.03, and 0.08 mg/kg for lead and 0.001, 0.002, and 0.005 mg/kg for mercury. No significant changes were observed in the tissue arsenic and mercury levels during the investigated period. A decrease was observed in the cadmium and lead concentrations in livers and kidneys. The provisional Dutch legal limits were exceeded only for lead in one kidney sample. A significant recti linear relation was found between the cadmium concentrations in livers and kidneys. In general the cadmium and lead levels found are comparable with published data, reported from other countries. Compared with data from the literature, the arsenic and mercury concentrations found in the present study are low.

ヒ素代謝に関する研究(第17報)ヒ素の胎仔移行，それにおよぼす解毒剤ならびに飼料の影響に関する研究

Albino rats of Wistar strain (Tamura 1950) breeded in a closed colony were administered arsenic trioxide orally during pregnancy (from the 0 day to the 20th day). Organs of fetuses and mother rats were exenterated on the 21st day of gestation and the contents of arsenic measured using an arsenic analyzer unit with atomic absorption spectrophotometry. Whole organs of the fetus were separated into 3 groupings i.e. liver, brain and remaining organs. The contents of arsenic in the organs in each of these groupings and in the placenta were measured. Even in the non-administered group, arsenic was detected in the every organ. In the arsenic administered group, the content of arsenic in the placenta was the highest among the four preparations tested; and the content in the liver and remaining organs was considerably high, but was low in the brain. The level of accumulation of arsenic differed between each organ. In the placenta, the accumulation reached a plateau, and in the brain this accumulation was below one-tenth that in the liver. In the non-administered group, arsenic was detected in the liver, kidney, spleen and brain of mother rats. In the group on arsenite, the content in the kidney and spleen was large, followed by a large amount in the liver and in the brain respectively. The level of accumulation of arsenic in mother rats differed between each organ. Arsenite was administered with antidotes such as dimercaprol, thioctic acid and L-ascorbic acid during pregnancy (from the 0 day to the 5th day). In this group the content of arsenic in the remaining organs was statistically less than that of the control group. The content in the brain was slightly reduced by a co-administration of the antidotes, however, there was no statistical difference in the placenta and liver between the antidote-treated and control groups. The content of arsenic in the kidney of mother rats treated with antidotes was statistically less than that of the controls. Whether or not the content of arsenic in organs of fetuses and mother rats was affected by a milk diet was also studied. The content of arsenic in the organs of fetuses showed no statistical difference between the animals on an Oriental stock diet group and those on the milk diet. On the other hand, the content of arsenic in the kidney of mother rats on the milk diet was statistically less than seen in those in the Oriental stock diet group.