RESUMO
Metal phthalocyanines are promising components in photodynamic therapy. Aluminum phthalocyanine chloride (AlClPc) has been used to treat oral cancer in mice, human carious tissue, lung cancer cells and other conditions. To overcome the high hydrophobicity of AlClPc, phthalocyanine is often encapsulated in nanoformulations. Despite increased usage, little is known about the pharmacokinetics and biodistribution of AlClPc. The aim of this study was the development and validation of a UHPLC-MS method for the determination of AlClPc in solution after extraction from nanoformulations and biological matrices such as plasma and tissue. The described method has been assayed as to selectivity, linearity, limits of detection and quantification, precision and recovery. The present study is the first to describe the behavior of AlClPc in biological matrices with mass spectrometry as well as the first to describe the chromatographic behavior of AlClPc contaminants. Molecular mass analysis identified dechlorination of AlClPc by both LC/MS and MALDI-MS and an adduct formation in LC/MS. The parameters observed indicated that the method has applicability and robustness for use in biodistribution studies.
Assuntos
Cromatografia Líquida de Alta Pressão/normas , Indóis/sangue , Nanoestruturas/química , Compostos Organometálicos/sangue , Fármacos Fotossensibilizantes/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/normas , Animais , Disponibilidade Biológica , Biotransformação , Óleo de Rícino/química , Sistemas de Liberação de Medicamentos , Emulsões , Humanos , Interações Hidrofóbicas e Hidrofílicas , Indóis/farmacocinética , Indóis/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Limite de Detecção , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/administração & dosagem , Compostos Organometálicos/farmacocinética , Compostos Organometálicos/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Baço/efeitos dos fármacos , Baço/metabolismo , Distribuição TecidualRESUMO
The objective of this study was to evaluate markers of oxidative stress in the brains of rats exposed to lead acetate (Pb(C2 H3 O2 )2 ), either associated or not associated with ferrous sulfate (FeSO4 ). A total of 36 weaning rats (Rattus norvegicus) were divided into 6 groups of six animals and exposed to lead acetate for six weeks. In the control group (control), the animals received deionized water. The Pb260 and Pb260 + Fe received 260 µM lead acetate, and the Pb1050 and Pb1050 + Fe received 1050 µM lead acetate. The Pb260 + Fe and Pb1050 + Fe were supplemented with 20 mg of ferrous sulfate/Kg body weight every 2 days. Group Fe received deionized water and ferrous sulfate. The rat brains were collected to analyze the enzymatic activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the concentration of reduced glutathione (GSH), lipid peroxidation (TBARS), and total antioxidant substance (TAS) (DPPH⢠technique). The activity of SOD and GPx in the experimental groups decreased compared to the control, together with the concentration of GSH (p < 0.05). For CAT analysis, SOD tended to increase in concentration in the experimental groups without a concomitant exposure to FeSO4 , whereas GPx showed a slight tendency to increase in activity compared to the control. For TAS-DPPH⢠, there was a decrease in the experimental groups (p < 0.05). According to the results, SOD, GPx, and GSH were affected by lead acetate and exposure to ferrous sulfate changed this dynamic. However, further studies are needed to verify whether ferrous sulfate acts as a protectant against the toxic effects of lead. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 813-822, 2017.
Assuntos
Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Compostos Ferrosos/farmacologia , Compostos Organometálicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/química , Peso Corporal/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Compostos Organometálicos/análise , Compostos Organometálicos/sangue , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Analytical and bioanalytical methods of high-performance liquid chromatography with fluorescence detection (HPLC-FLD) were developed and validated for the determination of chloroaluminum phthalocyanine in different formulations of polymeric nanocapsules, plasma and livers of mice. Plasma and homogenized liver samples were extracted with ethyl acetate, and zinc phthalocyanine was used as internal standard. The results indicated that the methods were linear and selective for all matrices studied. Analysis of accuracy and precision showed adequate values, with variations lower than 10% in biological samples and lower than 2% in analytical samples. The recoveries were as high as 96% and 99% in the plasma and livers, respectively. The quantification limit of the analytical method was 1.12 ng/ml, and the limits of quantification of the bioanalytical method were 15 ng/ml and 75 ng/g for plasma and liver samples, respectively. The bioanalytical method developed was sensitive in the ranges of 15-100 ng/ml in plasma and 75-500 ng/g in liver samples and was applied to studies of biodistribution and pharmacokinetics of AlClPc.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Indóis/análise , Indóis/sangue , Fígado/metabolismo , Nanopartículas/análise , Compostos Organometálicos/análise , Compostos Organometálicos/sangue , Animais , Disponibilidade Biológica , Feminino , Indóis/farmacocinética , Limite de Detecção , Modelos Lineares , Camundongos , Compostos Organometálicos/farmacocinética , Reprodutibilidade dos Testes , Espectrometria de Fluorescência/métodos , Distribuição TecidualRESUMO
The biological effects of lead are well defined; however, neither the risk exposure level nor the subcellular mechanism of its action is completely clear. The present work was undertaken to investigate the effects of low level and long term lead exposure on the composition and expression of rat renal gangliosides. In order to identify ganglioside expression, frozen sections of kidneys were stained with monoclonal antibodies GMB16 (GM1 specific), GM28 (GM2 specific), AMR-10 (GM4 specific) and CDW 60 (9-O-Ac-GD3 specific). Strong reactivity was observed for GMB28, AMR-10 and CDW 60, while GMB16 developed only weak labelling in treated kidney compared with the control. The alterations in the expression of renal gangliosides observed by immunohistochemistry were accompanied by quantitative and qualitative changes in the thin layer chromatography of total gangliosides isolated from kidney tissues. Lead treatment produced a significant increase in 9-O-Ac GD3, a ganglioside involved in apoptotic processes. In agreement with this result, a significant decrease in the number of apoptotic glomerular cells was observed with the TUNEL assay. These findings lead us to suggest that alterations in renal gangliosides produced by low level lead exposure are associated with the apoptotic processes that take place in the kidney. These findings provide evidence that low level and long term lead exposure produces renal ganglioside alterations with urinary microalbumin excretion. The results suggest that lead levels within the limits of biological tolerance already cause molecular renal damage without clinical signs of toxicity.
Assuntos
Gangliosídeos/metabolismo , Nefropatias/etiologia , Rim/metabolismo , Intoxicação por Chumbo/complicações , Albuminúria/etiologia , Albuminúria/metabolismo , Animais , Apoptose , Peso Corporal , Cromatografia em Camada Fina , Modelos Animais de Doenças , Ingestão de Alimentos , Gangliosídeo G(M1)/metabolismo , Gangliosídeo G(M2)/metabolismo , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Intoxicação por Chumbo/metabolismo , Intoxicação por Chumbo/patologia , Masculino , Compostos Organometálicos/sangue , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The temperature and pH effects on the equilibrium of a blood plasma model have been studied on the basis of artificial neural networks. The proposed blood plasma was modeled considering two important metals, calcium and magnesium, and six ligands, namely, alanate, carbonate, citrate, glycinate, histidinate and succinate. A large data set has been used to simulate different concentrations of magnesium and calcium as a function of temperature and pH and these data were used for training the neural network. The proposed model allowed different types of analyses, such as the effects of pH on calcium and magnesium concentrations, the competition between calcium and magnesium for ligands and the effects of temperature on calcium and magnesium concentrations. The model developed was also used to predict how the variation of calcium concentration can affect magnesium concentrations. A comparison of neural network predictions against experimental data produced errors of about 3%. Moreover, in agreement with experimental measurements (Wang et al. in Arch. Pathol. 126:947-950, 2002; Heining et al. in Scand. J. Clin. Lab. Invest. 43:709-714, 1983), the artificial neural network predicted that calcium and magnesium concentrations decrease when pH increases. Similarly, the magnesium concentrations are less sensitive than calcium concentrations to pH changes. It is also found that both calcium and magnesium concentrations decrease when the temperature increases. Finally, the theoretical model also predicted that an increase of calcium concentrations will lead to an increase of magnesium concentration almost at the same rate. These results suggest that artificial neural networks can be efficiently applied as a complementary tool for studying metal ion complexation, with especial attention to the blood plasma analysis.
Assuntos
Cálcio/sangue , Magnésio/sangue , Redes Neurais de Computação , Humanos , Concentração de Íons de Hidrogênio , Ligantes , Compostos Organometálicos/sangue , TemperaturaRESUMO
The objective of this study was to investigate circadian variations of blood and milk lead toxicokinetics in dairy cows in summer. Twenty lactating Holstein animals were randomly assigned to four treatments corresponding to different hours after onset of light (HALO): 2, 8, 14, and 20. Cows received a single intravenous administration of 2.5 mg/kg lead as lead acetate. Blood and milk samples were taken and analyzed by atomic absorption spectrophotometry. For each toxicokinetic parameter, a one-way analysis of variance (ANOVA) was performed to outline the existence of daily variations. Significant blood differences as a function of HALO were found for the hybrid constant of distribution (alpha), hybrid constant of elimination (beta), elimination half-life (t(1/2)beta), area under the curve (AUC), volume of distribution at steady state (V(ss)) and clearance (Cl(B)) (p<0.05). Half-life of elimination presented two peaks at 2 and 14 HALO. Milk data showed significant differences for maximum concentration and AUC (p<0.05). The ratio AUC(milk)/AUC(blood) was utilized to estimate penetration of lead in milk. It differed significantly throughout the day (p<0.05). Milk data for the significant parameters could be fitted to circadian rhythms. No circadian rhythms were detected in blood parameters or in the ratio AUC(milk)/AUC(blood).
Assuntos
Bovinos/metabolismo , Ritmo Circadiano , Chumbo/análise , Leite/química , Compostos Organometálicos/farmacocinética , Animais , Feminino , Injeções Intravenosas , Lactação/metabolismo , Chumbo/sangue , Compostos Organometálicos/sangue , Farmacocinética , Estações do AnoRESUMO
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.
Assuntos
Eritrócitos/diagnóstico por imagem , Meglumina/farmacologia , Compostos Organometálicos/farmacologia , Compostos Radiofarmacêuticos/farmacocinética , Tecnécio/farmacocinética , Animais , Proteínas Sanguíneas/metabolismo , Eritrócitos/efeitos dos fármacos , Marcação por Isótopo , Masculino , Meglumina/sangue , Antimoniato de Meglumina , Compostos Organometálicos/sangue , Cintilografia , Compostos Radiofarmacêuticos/sangue , Ratos , Estatísticas não Paramétricas , Tecnécio/sangue , Compostos de Estanho/sangue , Distribuição Tecidual/efeitos da radiaçãoRESUMO
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.
Assuntos
Animais , Masculino , Ratos , Eritrócitos , Meglumina/farmacologia , Compostos Organometálicos/farmacologia , Compostos Radiofarmacêuticos/farmacocinética , Tecnécio/farmacocinética , Proteínas Sanguíneas/metabolismo , Eritrócitos/efeitos dos fármacos , Marcação por Isótopo , Meglumina/sangue , Compostos Organometálicos/sangue , Compostos Radiofarmacêuticos/sangue , Estatísticas não Paramétricas , Tecnécio/sangue , Compostos de Estanho/sangue , Compostos de Estanho , Distribuição Tecidual/efeitos da radiaçãoRESUMO
Organochalcogens are important intermediates and useful reagents in organic synthesis, which can increase human exposure risk to these chemicals in the workplace. As well, there are a number of reported cases of acute toxicity following organochalcogen ingestion of vitamins and dietary supplements. Since, the erythrocytic delta-ALA-D activity could be an important indicator of toxicity this report investigated the organochalcogens effects on blood delta-ALA-D in vitro. To investigate a possible involvement of cysteinyl groups in the inhibitory actions of diphenyl diselenide, diphenyl ditelluride and Ebselen (4-100 micro M), the effects of thiol reducing agents (0-3 mM) or zinc chloride (0-2 mM) were examined. Diphenyl ditelluride, diphenyl diselenide and Ebselen inhibited in a concentration-dependent manner delta-ALA-D activity from human erythrocytes. Ebselen was lesser delta-ALA-D inhibitor than (PhSe)(2) and (PhTe)(2), whereas the diorganoyldichalcogenides displayed similar inhibitory potency towards delta-ALA-D. Dithiothreitol, a hydrophobic SH-reducing agent, was able to reactivate and to protect inhibited delta-ALA-D. The pre-incubation of blood with the inhibitors changed considerably the reversing potency of thiols. From these findings we suggest that organochalcogens inactivate in vitro human erythrocyte delta-ALA-D by an interaction with the sulfhydryl group essential of the enzyme activity.
Assuntos
Antioxidantes/toxicidade , Azóis/toxicidade , Derivados de Benzeno/toxicidade , Dissulfetos/toxicidade , Eritrócitos/efeitos dos fármacos , Compostos Organometálicos/toxicidade , Compostos Organosselênicos/toxicidade , Sintase do Porfobilinogênio/metabolismo , Azóis/antagonistas & inibidores , Azóis/sangue , Derivados de Benzeno/antagonistas & inibidores , Derivados de Benzeno/sangue , Cisteína/farmacologia , Dissulfetos/antagonistas & inibidores , Dissulfetos/sangue , Ditiotreitol/farmacologia , Interações Medicamentosas , Eritrócitos/enzimologia , Glutationa Transferase/farmacologia , Humanos , Isoindóis , Compostos Organometálicos/antagonistas & inibidores , Compostos Organometálicos/sangue , Compostos Organosselênicos/antagonistas & inibidores , Compostos Organosselênicos/sangue , Sintase do Porfobilinogênio/antagonistas & inibidores , Zinco/farmacologiaRESUMO
A sensitive and specific liquid chromatographic method using solid-phase extraction with Sep-pak cartridges has been developed for the determination of Casiopeina IIgly and validated over the linear range 2.5-50 microg/ml in rat plasma. The analysis was performed on a Symetry C(18) (5 microm) column with a Phenomenex C(18) precolumn. The mobile phase was methanol-water (58:42, v/v). The column effluent was monitored at 273 nm. The results showed that the assay is sensitive at 2.5 microg/ml. Maximum intra-day coefficient of variation was 11.47%. The recovery based upon addition of internal standard to rat plasma was 80.98%. The method was used to perform preclinical pharmacokinetic studies in rat plasma and was found to be satisfactory.
Assuntos
Cobre/sangue , Compostos Organometálicos/sangue , Animais , Calibragem , Masculino , Compostos Organometálicos/farmacocinética , Ratos , Ratos Wistar , Padrões de Referência , Sensibilidade e EspecificidadeRESUMO
A sensitive and specific liquid chromatographic method using extraction with zinc sulfate has been developed for the determination of Casiopeina IIIi and validated over the linear range 5-100 microg/ml in 1 ml of rat plasma. The analysis was performed on a Symmetry C(18) (5 microm) column. The mobile phase was methanol: 0.01 M phosphate buffer pH 6.5 (40:60, v/v). The column effluent was monitored at 262 nm. The results showed that the assay is sensitive at 5 microg/ml. Maximum intra-day coefficient of variation was 10.6%. The recovery obtained in plasma was 87.2%. The method was used to perform protein binding studies by equilibrium dialysis in rat plasma and was found to be satisfactory.
Assuntos
Antineoplásicos/sangue , Cromatografia Líquida/métodos , Compostos Organometálicos/sangue , Animais , Antineoplásicos/farmacocinética , Calibragem , Masculino , Compostos Organometálicos/farmacocinética , Ratos , Ratos Wistar , Sensibilidade e Especificidade , Espectrofotometria UltravioletaRESUMO
Wistar dams were exposed to 500 ppm of Pb, as Pb acetate, or 660 ppm Na acetate in drinking water during pregnancy and lactation. Male pups at 23 (weaned) or 70 days (adult) of age were submitted to behavioral evaluation and Pb determination. The behaviors evaluated were: locomotor activity (open-field test), motor coordination (rotarod test), exploratory behavior (holeboard test), anxiety (elevated plus maze and social interaction tests), and learning and memory (shuttle box). Pb levels were measured in the blood and cerebral regions (hippocampus and striatum) of dams and pups. The results of the present report demonstrated that exposure to Pb during pregnancy and lactation induces in weaned pups hyperactivity, decreased exploratory behavior, and impairment of learning and memory. These alterations were observed at blood Pb levels in the range that may be attained in children chronically exposed to low levels of Pb (21+/-3 microg/dl). Regarding adults, the results demonstrated that the regimen of exposure adopted induces anxiety in these animals at nondetectable blood Pb levels.
Assuntos
Envelhecimento/fisiologia , Chumbo/toxicidade , Compostos Organometálicos/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Animais , Ansiedade/induzido quimicamente , Peso Corporal/efeitos dos fármacos , Encéfalo/metabolismo , Comportamento Exploratório/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Feminino , Lactação , Chumbo/sangue , Chumbo/farmacocinética , Atividade Motora/efeitos dos fármacos , Compostos Organometálicos/sangue , Compostos Organometálicos/farmacocinética , Gravidez , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Wistar , Fatores de Tempo , Abastecimento de ÁguaRESUMO
Neurotoxicity associated with lead exposure may be the result of a series of small perturbations in brain metabolism, and, in particular, of oxidative stress. Some studies have suggested a lead-induced enhancement on lipid peroxidation as a possible mechanism for some toxic effects of lead. However, there are no reports about the association between lipid peroxidation enhancement and brain lead content. In this study, we determined the concentration of lead and the formation of lipid fluorescence products in the blood, as well as in the parietal cortex, striatum, hippocampus, thalamus, and cerebellum of rats exposed prenatally and postnatally to variable concentrations of lead acetate through drinking water. Pregnant Wistar rats were intoxicated throughout gestation with solutions containing either 320 or 160 ppm of lead. The pups were treated after birth in the same way until 45 days of age. Control animals received deionized water for the same period of time. The developing rats were sacrificed at postnatal day 45 and lead level was assessed biochemically in the blood and different brain regions. Results showed that blood lead levels were increased in a dose-dependent manner. In the brain, lead accumulated preferentially in the parietal cortex, striatum, and thalamus as compared to the control group, while lipid fluorescence products were significantly increased in the striatum, thalamus, and hippocampus of the treated animals. These data suggest that in the brain of rats exposed to lead acetate, lead produces a neurotoxic effect with a complex correlation with both lead regional content and lipid peroxidation.
Assuntos
Encéfalo/efeitos dos fármacos , Intoxicação do Sistema Nervoso por Chumbo na Infância/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Compostos Organometálicos/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Animais , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Criança , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Intoxicação do Sistema Nervoso por Chumbo na Infância/fisiopatologia , Peroxidação de Lipídeos/fisiologia , Neurônios/metabolismo , Compostos Organometálicos/sangue , Compostos Organometálicos/farmacocinética , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Gravidez , Ratos , Ratos Wistar , Poluentes Químicos da Água/farmacocinética , Poluentes Químicos da Água/toxicidadeRESUMO
Bismuth subsalicylate (BSS) and placebo were evaluated in a double-blind, placebo-controlled study as adjunct to rehydration therapy in 123 children, aged 4 to 28 months, hospitalized with acute diarrhea. The dosing regimen was 20 mg/kg five times daily for 5 days. Significant benefits were noted in the BSS group compared with placebo as manifested by decreases in stool frequency and stool weights and an improvement in stool consistency, significant improvement in clinical well-being, and shortening of the disease duration. Patients treated with BSS had a significant reduction in duration of hospital stay (6.9 days) compared with placebo-treated patients (8.5 days). Also, intravenous fluid requirements decreased significantly more rapidly and to a greater degree in the BSS-treated group. Bismuth subsalicylate was associated with clearance of pathogenic Escherichia coli from the stools in 100% of cases but was not different from placebo in rotavirus elimination. Bismuth subsalicylate was well tolerated with no reported adverse effects. Blood bismuth and serum salicylate levels were well below levels considered toxic. In this study, BSS provided effective adjunctive therapy for acute diarrhea, allowing children to get well sooner with less demand on the nursing and hospital staff.