Hepatic, Metabolic, and Toxicity Evaluation of Repeated Oral Administration of SnS2 Nanoflowers in Mice.

Tin sulfide (SnS2) nanoflowers (NFs) with highly photocatalytic activity for wastewater treatment may lead to potential health hazards via oral routes of human exposure. No studies have reported the hepatic effects of SnS2 NFs on the metabolic function and hepatotoxicity. In this study, we examined the hepatic effects of the oral administration of SnS2 NFs (250-1000 mg/kg) to ICR mice for 14 days, with the particle size ranging from 50 to 200 nm. Serum and liver tissue samples were assayed using biochemical analysis, liver histopathology and metabolic gene expression. The different sizes of SnS2 NFs (250 mg/kg dose), such as 50, 80, and 200 nm, did not induce any adverse hepatic effect related to biochemical parameters or histopathology in the treated mice compared with controls. The oral administration of 50-nm SnS2 NFs at doses of 250, 500, and 1000 mg/kg for 14 days produced dose-dependent hepatotoxicity and inflammatory responses in treated mice. Furthermore, the expression of metabolic genes in the liver tissues was altered, supporting the SnS2 NF-related hepatotoxic phenotype. The oral administration of SnS2 NFs also produced abnormal microstructures in the livers of the treated mice. Taken together, these data indicate that the increased risk of hepatotoxicity in SnS2 NF-treated mice was independent of the particle size but was dependent on their dose. The no-observed-adverse effect level was <250 mg/kg for the 50-nm SnS2 NFs. Our study provides an experimental basis for the safe application of SnS2 NFs.

An advanced case of indium lung disease with progressive emphysema.

OBJECTIVES: To report the occurrence of an advanced case of indium lung disease with severely progressive emphysema in an indium-exposed worker. CASE REPORT: A healthy 42-year-old male smoker was employed to primarily grind indium-tin oxide (ITO) target plates, exposing him to indium for 9 years (1998-2008). In 2004, an epidemiological study was conducted on indium-exposed workers at the factory in which he worked. The subject's serum indium concentration (In-S) was 99.7 µg/l, while his serum Krebs von den Lungen-6 level was 2,350 U/ml. Pulmonary function tests showed forced vital capacity (FVC) of 4.17 l (91.5% of the JRS predicted value), forced expiratory volume in 1 s (FEV1) of 3.19 l (80.8% of predicted), and an FEV1-to-FVC ratio of 76.5%. A high-resolution chest computed tomography (HRCT) scan showed mild interlobular septal thickening and mild emphysematous changes. In 2008, he was transferred from the ITO grinding workplace to an inspection work section, where indium concentrations in total dusts had a range of 0.001-0.002 mg/m3. In 2009, the subject's In-S had increased to 132.1 µg/l, and pulmonary function tests revealed obstructive changes. In addition, HRCT scan showed clear evidence of progressive lung destruction with accompanying severe centrilobular emphysema and interlobular septal thickening in both lung fields. The subject's condition gradually worsened, and in 2015, he was registered with the Japan Organ Transplant Network for lung transplantation (LTx). CONCLUSIONS: Heavy indium exposure is a risk factor for emphysema, which can lead to a severity level that requires LTx as the final therapeutic option.

Comparing plasma, serum and whole blood indium concentrations from workers at an indium-tin oxide (ITO) production facility.

OBJECTIVE: Occupational exposure to indium compounds including indium-tin oxide (ITO) can result in potentially fatal indium lung disease. We compared plasma, serum and whole blood indium concentrations (InP, InS and InB) from workers at a single ITO production facility to assess the comparability of these matrices used for biological monitoring of indium exposure. METHOD: InP, InS and InB were measured using inductively coupled mass spectrometry from consenting workers at an ITO production facility with specimen collection occurring during June-July 2014. Matched pairs from workers were assessed to determine the matrix relationships using the Pearson correlation, paired t-tests, per cent difference, linear regression and κ statistics. RESULTS: Indium matrices were collected from 80 workers. Mean (SD) InP, InS and InB were 3.48 (3.84), 3.90 (4.15) and 4.66 (5.32) mcg/L, respectively. The InS-InP difference was 14%; InS was higher in all but two workers. InP and InS were highly correlated (r=>0.99). The InB-InS difference was 19%; InB was higher in 85% of workers. The InB-InP difference was 34%; InB was higher in 66% of workers. InB was highly correlated with both InP and InS (r=0.97 and 0.96, respectively). κ Statistics were 0.84, 0.83 and 0.82 for InP, InS and InB, respectively, for individuals with each matrix ≥1 mcg/L (p<0.01). CONCLUSIONS: While all matrices were highly correlated, we encourage the use of InP and InS to reliably compare studies across different populations using different matrices. The higher per cent difference and increased variability of InB may limit its utility in comparisons with InP and InS in different populations.

Early changes in clinical, functional, and laboratory biomarkers in workers at risk of indium lung disease.

RATIONALE: Occupational exposure to indium compounds, including indium-tin oxide, can result in potentially fatal indium lung disease. However, the early effects of exposure on the lungs are not well understood. OBJECTIVES: To determine the relationship between short-term occupational exposures to indium compounds and the development of early lung abnormalities. METHODS: Among indium-tin oxide production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. Relationships between plasma indium concentration and health outcome variables were evaluated using restricted cubic spline and linear regression models. MEASUREMENTS AND MAIN RESULTS: Eighty-seven (93%) of 94 indium-tin oxide facility workers (median tenure, 2 yr; median plasma indium, 1.0 µg/l) participated in the study. Spirometric abnormalities were not increased compared with the general population, and few subjects had radiographic evidence of alveolar proteinosis (n = 0), fibrosis (n = 2), or emphysema (n = 4). However, in internal comparisons, participants with plasma indium concentrations ≥ 1.0 µg/l had more dyspnea, lower mean FEV1 and FVC, and higher median serum Krebs von den Lungen-6 and surfactant protein-D levels. Spline regression demonstrated nonlinear exposure response, with significant differences occurring at plasma indium concentrations as low as 1.0 µg/l compared with the reference. Associations between health outcomes and the natural log of plasma indium concentration were evident in linear regression models. Associations were not explained by age, smoking status, facility tenure, or prior occupational exposures. CONCLUSIONS: In indium-tin oxide facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, decreased spirometric parameters, and increased serum biomarkers of lung disease.

Inhalation carcinogenicity and chronic toxicity of indium-tin oxide in rats and mice.

OBJECTIVES: Carcinogenicity and chronic toxicity of indium-tin oxide (ITO) were examined by inhalation exposure of rats and mice to ITO aerosol. METHODS: Fifty mice of both sexes were exposed to ITO at 0 (control), 0.01, 0.03 or 0.1 mg/m(3) for 6 h/day, 5 day/wk for 104 wk, and 50 rats of both sexes were exposed to 0, 0.01 or 0.03 mg/m(3) ITO for the same time period. The repeated exposure of 50 rats of both sexes to 0.1 mg/m(3) ITO was discontinued at the 26th wk, followed by clean air exposure for the remaining 78 wk. RESULTS: In rats, incidences of bronchiolo-alveolar adenomas and carcinomas, bronchiolo-alveolar hyperplasia, alveolar wall fibrosis and thickened pleural wall, alveolar proteinosis and infiltrations of alveolar macrophages and inflammatory cells were significantly increased. Combined incidences of malignant lung tumors in male rats and total lung tumors in male and female rats were significantly increased at exposure to 0.01 mg/m(3) ITO. In mice, no carcinogenic response occurred, but thickened pleural wall, alveolar proteinosis and alveolar macrophage infiltration were induced. Mice were less susceptible to ITO than rats. The lung content of indium was the greatest, followed by the spleen, kidney and liver. Blood indium levels increased dose-dependently. CONCLUSIONS: There was clear evidence of carcinogenicity of inhaled ITO in male and female rats but not clear evidence in mice, together with occurrence of the chronic pulmonary lesions in both rats and mice.

Pulmonary toxicity in mice by 2- and 13-week inhalation exposures to indium-tin oxide and indium oxide aerosols.

OBJECTIVES: Inhalation toxicities of indium-tin oxide (ITO) and indium oxide (IO) in mice were characterized in comparison with those previously reported in rats. METHODS: B6C3F(1) mice of both sexes were exposed by inhalation to ITO or IO aerosol for 6 h/day, 5 day/wk for 2 wk at 0, 0.1, 1, 10 or 100 mg/m(3) or 13 wk at 0, 0.1or 1 mg/m(3). RESULTS: ITO and IO particles were deposited in the lung, mediastinal lymph node (MLN) and nasal-associated lymphoid tissue. Alveolar proteinosis, infiltrations of alveolar macrophages and inflammatory cells and increased lung weight were induced by 2- and 13-week exposures to ITO and IO, while alveolar epithelial hyperplasia occurred only in the 2-week exposures. Thickened pleural wall, hyperplastic MLN, extramedullary hematopoiesis in the spleen and increased levels of erythrocyte parameters were induced by 13-week exposure to ITO. The ITO- and IO-induced pulmonary lesions were milder in mice than those previously reported in rats, and the fibrotic lesions were different between these two species. Indium levels in the lung and pooled blood were analyzed in the mice exposed to ITO and IO for 13 wk. In the 13-week inhalation exposure of mice to ITO, alveolar proteinosis and significantly increased lung weight were induced at the same exposure concentration as the current threshold limit value for indium and its compounds.

Two- and 13-week inhalation toxicities of indium-tin oxide and indium oxide in rats.

OBJECTIVES: Two- and 13-week inhalation toxicities of indium-tin oxide (ITO) and indium oxide (IO) were characterized for risk assessments of workers exposed to ITO. METHODS: F344 rats of both sexes were exposed by inhalation to ITO or IO aerosol for 6 h/day, 5 day/wk for 2 wk at 0, 0.1, 1, 10 or 100 mg/m(3) or 13 wk at 0, 0.1 or 1 mg/m(3). An aerosol generator and inhalation exposure system was constructed. RESULTS: Blood and lung contents of indium were elevated in a dose-related manner in the ITO- and IO-exposed rats. ITO and IO particles were deposited in the lung, mediastinal lymph node and nasal-associated lymphoid tissue. Exposures to ITO and IO induced alveolar proteinosis, infiltrations of alveolar macrophages and inflammatory cells and alveolar epithelial hyperplasia in addition to increased lung weight. ITO affected the lung more severely than IO did. Fibrosis of alveolar wall developed and some of these lesions worsened at the end of the 26-week post-exposure period. CONCLUSIONS: Persistent pulmonary lesions including alveolar proteinosis and macrophage infiltration occurred after 2- and 13-week inhalation exposures of rats to ITO and IO. Fibrosis of alveolar wall developed later. These lesions occurred after ITO exposure at the same concentration as the current occupational exposure limit in the USA and at blood indium levels below the biological exposure index in Japan for indium.

In vitro evaluation of feline leukocytes radiolabeled in whole blood with 99mTc stannous colloid.

Technetium-99m stannous colloid (9mTcSnC) has been used to radiolabel human leukocytes to investigate various inflammatory disorders. We investigated the in vitro behavior of feline leukocytes labeled in whole blood with 99mTcSnC. Heparinized blood samples were collected from healthy cats and divided into control and test aliquots. The latter were labeled with 99mTcSnC using a standard procedure. Leukocyte viability was determined for each sample using a trypan blue exclusion test. Labeling efficiency was determined for test aliquots. Test aliquots were layered onto Histopaque-1077 and centrifuged before measurement of radioactivity of the blood components. Leukocytes from radiolabeled and control samples were washed and incubated with opsonized zymosan particles to allow assessment of phagocytic function. Aliquots were taken from radiolabeled feline leukocyte samples at 1, 3, 4, and 7 h postlabelling. After centrifugation of each aliquot, radioactivity of the supernatant and pellet was measured and the labeling retention determined. Leukocyte viability in both radiolabeled and control samples was > 98%. The labeling efficiency was 95.2 +/- 0.14%. The distribution of radioactivity in feline blood was found to be 3.4 +/- 0.18% in plasma, 39.0 +/- 0.37% in erythrocytes, and 57.6 +/- 0.38% in leukocytes. Labeled feline leukocytes had phagocytic activity of 90.9 +/- 0.18% (control 91.3 +/- 0.15%). The radiolabeled leukocytes retained 93.4 +/- 0.19% of the radioactivity up to 7h postlabeling. 99TcSnC efficiently labeled feline leukocytes with no effect on viability and minimal effect on phagocytic function. The percentage retention of radioactivity by the leukocytes was still high at 7h postlabeling.

Spectrophotometric determination of Sb(III) and Sb(V) in biological samples after micelle-mediated extraction.

This work presents a micelle-mediated extraction method for simultaneous preconcentration and determination of Sb(III) and Sb(V) species in biological samples as a prior preconcentration step to their spectrophotometric determination. The analytical system is based on the selective reaction between Sb(III) and bromopyrogallol red (BPR) in the presence of cetyltrimethylammonium bromide (CTAB) and potassium iodide at pH 6.4. Total Sb concentration was determined after reduction of Sb(V) to Sb(III) in the presence of potassium iodide and ascorbic acid. The optimal extraction and reaction conditions were studied and the analytical characteristics of the method (e.g., limit of detection, linear range, preconcentration factor, and improvement factors) were obtained. Linearity for Sb(III) and Sb(V) were obeyed in the range of 0.2-20.0 ng mL(-1) and 0.4-25.0 ng mL(-1), respectively. The detection limit for the determination of Sb(III) and Sb(V) were 0.05 ng mL(-1) and 0.08 ng mL(-1), respectively. The interference effect of some anions and cations was also studied. The method was applied to the determination of Sb(III) in the presence of Sb(V) and total antimony in blood plasma and urine samples.

[Three cases of indium lung].

The production of indium tin oxide (ITO) has been increasing during the past decade because of its use in liquid crystal and plasma display panels. Following the first report on lethal lung injury in a ITO worker in 2001, we began pulmonary check-ups for 115 workers in the plant in our capacity of industrial physicians of the plant. Hence, we report interstitial pulmonary disease in 3 workers who had engaged in wet-surface grinding of ITO for 8 to 12 years and had significant lung injuries. The serum indium level and serum concentration of KL-6 were significantly elevated in all 3 cases. One non-smoker case among them showed severe obstructive changes on spirometry and had an episode of repeated bilateral pneumothorax before and during the follow-up period. All 3 cases showed both interstitial and/or emphysematous changes on HRCT. It is suggested that inhaled indium compounds can cause a new and unique interstitial pulmonary disease.

In whole blood, LPS, TNF-alpha and GM-CSF increase monocyte uptake of 99mtechnetium stannous colloid but do not affect neutrophil uptake.

INTRODUCTION: (99m)Technetium stannous colloid (TcSnC) is used in white cell scanning. It labels neutrophils and monocytes via phagocytosis, with uptake mediated by the phagocytic receptor CD11b/CD18 in neutrophils. Uptake of TcSnC is altered by gram-negative infection, possibly due to the endotoxin component lipopolysaccharide (LPS) or to cytokines released during infection (e.g., TNF-alpha and IFN-gamma). Endotoxemia and increased TNF-alpha levels also occur in inflammatory bowel disease. Another potential confounder in cell labeling is that sepsis patients may be treated with GM-CSF and G-CSF, which alter phagocytic cell function. This study aimed to determine how these factors affect TcSnC cellular uptake. METHODS: Whole blood from six healthy volunteers was incubated with LPS, TNF-alpha, IFN-gamma, GM-CSF or G-CSF. Samples were then mixed with TcSnC. Blood was separated across density gradients and imaged using a gamma camera. Three radioactive count peaks were observed in each tube: free plasma activity, mononuclear cell uptake and neutrophil uptake. RESULTS: Compared with controls, significant increases in mononuclear cell uptake were induced by LPS, TNF-alpha and GM-CSF stimulation. It was incidentally noted that exogenous estrogens appear to affect TcSnC labeling and may influence the neutrophil response to stimulation. Neutrophil uptake and plasma activity were not significantly affected. IFN-gamma and G-CSF had no significant effect. CONCLUSIONS: In whole blood, the effect of LPS on TcSnC monocyte uptake is different to its effect on neutrophils, consistent with previously reported differences in CD11b/CD18 expression. TNF-alpha response parallels LPS response. GM-CSF also increases TcSnC uptake by monocytes. These effects should be considered when using TcSnC for imaging purposes, as they will tend to increase monocyte labeling. Estrogens may also affect TcSnC labeling. Responses to IFN-gamma and G-CSF are consistent with previously reported effects of these cytokines on CD11b/CD18 expression.

[Effect of Hypericum perforatum extract on in vitro labelling of blood elements with technetium-99m and on biodisponibility of sodium pertechnetate in Wistar rats]. / Efeito de um extrato de Hipérico (Hypericum perforatum) na marcação in vitro de elementos sangüíneos com tecnécio-99m e na biodisponibilidade do radiofármaco pertecnetato de sódio em ratos Wistar.

PURPOSE: To evaluate the effect of a hiperico extract (Hypericum perforatum) on the labeling of blood elements with technetium-99m (99mTc) and in the bioavailability of the radiopharmaceutical sodium pertechnetate in Wistar rats. METHODS: Blood (heparinized) withdrawn from Wistar rats is incubated with a hiperico extract, with a stannous cloride and with 99mTc, as sodium pertechnetate (99mTcONa). Plasma (P) and cells (C) are isolated by centrifugation. Samples of P and C are also precipitated with trichloroacetic acid (TCA 5%) and soluble (FS-P; FS-C) and isoluble (FI-P; FI-C) fractions are separated. In the bioavailability analysis, the extract or NaCl 0.9% solution is administrated into Wistar rats (gavage) during 15 days. Sodium pertechnetate was administered and after 10 min, the animals are sacrificed, the organs were isolated, the radioactivity determined in a well counter, and the percentages of radioactivity per gram (%ATI/g) in the organs are calculated. RESULTS: The hiperico extract decreasedsignificantly (P < 0.05) the %ATI in the cells, cellular insoluble fraction and plasma insoluble fraction. The biodistribution was significantly (P < 0.01) decreased in bone, muscle and thyroid and significantly (P < 0.05) increased in pancreas. CONCLUSION: The analysis of the results indicates that in studied extract should have substances that should oxidize the stannous ion, reducing the fixation of the 99mTc on the erythrocytes and plasma and cellular proteins. Moreover, it could produce metabolic alterations with influence in the uptake of the radiopharmaceutical 99mTcO4Na in bone, muscle, pancreas and thyroid.

The effect of Glucantime on the labeling of blood constituents with technetium-99m.

PURPOSE: The labeling of red blood cells (C) with 99mTc is employed in clinical nuclear medicine for a variety of diagnostic procedures. Drugs can alter this labeling method and modify the disposition of the radiopharmaceuticals. In this paper, the influence of glucantime on the labeling of blood constituents with 9mTc was reported. METHODS: Blood was withdrawn from rats and incubated with glucantime. Stannous chloride and 99mTc were added. After centrifugation, plasma (P) and (C) were isolated. Samples of P and C were precipitated with TCA 5%, centrifuged and insoluble (IF) and soluble fractions (SF) separated. The percentages of total activity injected (%ATI) in C, IF-P and IF-C were calculated (p < 0.05). RESULTS: The %ATI on C decreased from control to following concentrations of glucantime (6.25%; 12.5%; 25%; 50%; 100%), respectively: 94.06 +/- 1.29 (control) to 77.15 +/- 2.79; to 76.68 +/- 1.88; to 75.15 +/- 2.79; to 72.64 +/- 4.40 and to 63.05 +/- 3.84. On IF-C the %ATI decreased from control to all the concentrations of glucantime (3.125%;6.25%; 12.5%; 25%; 50%; 100%), respectively: 93.34 +/- 1.18 (control) to 78.81 +/- 2.76; to 74.76 +/- 4.82; to 74.02 +/- 5.32; to 64.35 +/- 4.82; to 62.81 +/- 1.97 and to 54.55 +/- 3.58. CONCLUSIONS: This effect was probably due to products present in this drug that may complex with ions (Sn(+2) and 99mTcO4) or have a direct or indirect effect on intracellular stannous ion concentration.

Labeling efficiency and biodistribution of Technetium-99m labeled nanoparticles: interference by colloidal tin oxide particles.

The interference of colloidal tin oxides on the biodistribution of (99m)Technetium radiolabeled chitosan nanoparticles has been overcome by using sodium borohydride instead of commonly used stannous salts as reducing agent for the reduction of (99m)Tc (VII) to lower valency states. Biodistribution of radiolabeled chitosan nanoparticles prepared by using stannous chloride method revealed localization of the radioactivity mainly in the liver and spleen while that of radiolabeled chitosan nanoparticles prepared by using sodium borohydride method manifested the presence of radioactivity in blood up to an extent of 10% even after 2 h. Interestingly, the reduction of radioactivity in the latter case with the progress of time was not manifested through an increase in activity in the liver. Rather, a time dependent increased accumulation of radioactive materials was observed in the stomach. From the results it has been concluded that the biodistribution is strongly influenced by the presence of colloidal particles of tin oxides and (99m)Tc labeled chitosan nanoparticles are RES evading and long circulating in blood when Tc (VII) is reduced by sodium borohydride and not by stannous chloride during radiolabeling process.

Efeito de um extrato de Hipérico (Hypericum perforatum) na marcação in vitro de elementos sangüíneos com tecnécio-99m e na biodisponibilidade do radiofármaco pertecnetato de sódio em ratos Wistar / Effect of Hypericum perforatum extract on in vitro labelling of blood elements with technetium-99m and on biodisponibility of sodium pertecnetate in Wistar rats

OBJETIVO: Avaliar o efeito de um extrato de hipérico (Hypericum perforatum) na marcação de elementos sanguíneos com tecnécio-99m (99mTc) e na biodisponibilidade do radiofármaco pertecnetato de sódio em ratos Wistar. MÉTODOS: Sangue (heparinizado) de ratos Wistar é incubado com um extrato de hipérico, com cloreto estanoso e a seguir com Tc-99m, como pertecnetato de sódio (99mTcO4Na). Plasma (P) e células (CS) são isolados por centrifugação. Amostras de P e CS também são precipitadas com ácido tricloroacético 5 por cento, e separadas as frações solúveis (FS-P e FS-CS) e insolúveis (FI-P e FI-CS). Para a análise da biodistribuição, 0,3 mL do radiofármaco 99mTcO4Na foi administrada em ratos Wistar que receberam por gavagem extrato ou salina (NaCl 0,9 por cento) por 15 dias. Após 10 minutos os animais foram sacrificados e os órgãos isolados para contagem da atividade radioativa. RESULTADOS: O extrato de hipérico reduziu de forma significativa (P<0,05) a por centoATI ligada às células, à fração insolúvel celular e à fração insolúvel do plasma. A biodistribuição foi diminuída significativamente (P<0,01) no osso, no músculo e na tireóide. No pâncreas o percentual de radioatividade aumentou significativamente (P<0,05). CONCLUSÃO: No extrato vegetal estudado podem existir substâncias que oxidariam o íon estanoso, reduzindo a fixação do 99mTc às hemácias e proteínas plasmáticas e celulares. Da mesma forma poderiam produzir alterações metabólicas com conseqüente influência na captação do radiofármaco pertecnetato de sódio no osso, músculo, pâncreas e tireóide.

The effect of glucantime™ on the labeling of blood constituents with technetium-99m

OBJETIVO: A marcação de hemácias sangüíneas (C) com 99mTc é muito utilizada nos procedimentos diagnósticos na medicina nuclear. Drogas podem alterar este método de marcação e modificar a biodisponibilidade de radiofármacos. Neste trabalho, foi avaliada a influência de glucantime na marcação de elementos sangüíneos com 99mTc. MÉTODOS: Sangue foi retirado de ratos e incubado com glucantime. Adicionou-se cloreto estanoso e 99mTc. Após centrifugação, plasma (P) e (C) foram isolados. Amostras de P e C foram precipitadas com TCA 5 por cento, centrifugadas e separadas em frações solúveis (FS) e insolúveis (FI). Os percentuais de atividade total injetada (por cento ATI) em C, FI-P e FI-C foram calculados (p<0,05). RESULTADOS: O %ATI em C diminuiu, em relação ao controle, nas seguintes concentrações de glucantime (6,25 por cento;12,5 por cento; 25 por cento; 50 por cento; 100por cento), respectivamente: 94,06±1,29 (controle) para 77,15±2,79; para 76,68±1,88; para 75,15±2,79; para 72,64±4,40 e para 63,05±3,84. Em FI-C, o %ATI diminuiu, em relação ao controle, em todas as concentrações de glucantime (3,125 por cento; 6,25 por cento; 12, 5 por cento; 25 por cento; 50 por cento; 100 por cento), respectivamente: 93,34±1,18 (controle) para 78,81±2,76; para 74,76±4,82; para 74,02±5,32; para 64,35±4,82; para 62,81±1,97 e para 54,55±3,58. CONCLUSÕES: Este efeito provavelmente foi devido a produtos presentes nesta droga que podem se complexar com íons (Sn+2 e 99mTcO-4) ou ter um efeito direto ou indireto na concentração intracelular do íon estanoso.

Assessment of the effect of Maytenus ilicifolia (espinheira santa) extract on the labeling of red blood cells and plasma proteins with technetium-99m.

We are trying to develop a model to assess properties of products utilized in popular medicine. Maytenus ilicifolia is used in herbal medicine. Red blood cells (RBC) labeled with technetium-99m (99mTc) are employed in nuclear medicine. This labeling procedure depends on a reducing agent and stannous chloride is used. There is evidence that this labeling may be altered by drugs. We have investigated the possibility of M. ilicifolia extract being capable to alter the labeling of blood elements with 99mTc. Blood was incubated with M. ilicifolia extract. Stannous chloride solution and Tc-99m were added. Blood was centrifuged and plasma (P) and blood cells (C) were isolated. Samples of P or C were also precipitated, centrifuged and insoluble (IF) and soluble (SF) were separated. The percentages of radioactivity (%ATI) in C, IF-P and IF-C was calculated. The %ATI decreased on C from 93.6+/-2.3 to 29.0+/-2.7, on IF-P from 77.6+/-1.2 to 7.5+/-1.0 and on IF-C from 80.0+/-3.4 to 12.6+/-4.8. Once in RBC labeling procedure with 99mTc depends on the presence of stannous (+2) ions, the substances of the M. ilicifolia extract could increase the valence these ions to stannic (+4). This fact would decrease the %ATI on blood elements and indicate the presence of oxidant agents in the M. ilicifolia extract.

The effect of drugs on the labeling of blood elements with technetium-99m.

The influence of drugs on the labeling of red blood cells and plasma proteins with 99mTc has been reported. Any drug, which alters the labeling of the tracer, could be expected to modify the disposition of the radiopharmaceuticals. Red blood cells (RBC) labeled with technetium-99m (99mTc) are used for several evaluations in nuclear medicine. We have evaluated the effect of Thuya occidentalis, Peumus boldus and Nicotiana tabacum (tobacco) extracts on the labeling of RBC and plasma and cellular proteins with 99mTc. Blood was incubated with the drugs. Stannous chloride (SnCl2) solutions and 99mTc were added. Plasma (P) and blood cells (BC) were separated. The percentage of radioactivity (%ATI) bound to P and BC was determined. The %ATI on the plasma and cellular proteins was also evaluated by precipitation of P and BC samples with trichloroacetic acid (TCA) and isolation of soluble (SF) and insoluble (IF) fractions. The analysis of the results shows that there is a decrease in %ATI (from 97.64 to 75.89 percent) in BC with Thuya occidentalis extract. The labeling of RBC and plasma proteins can be decreased in presence of tobacco. This can be due either a direct or indirect effect (reactive oxygen species) of tobacco. The analysis of radioactivity in samples of P and BC isolated from samples of whole blood treated with Peumus boldus showed a rapid uptake of the radioactivity by blood cells in the presence of the Peumus boldus, whereas there was a slight decrease in the amount of 99mTc radioactivity in the TCA-insoluble fraction of plasma. This study shows that extracts of some medicinal plants can affect the radiolabeling of red blood cells with 99mTc using an in vitro technique.