Albendazole as a promising molecule for tumor control.

This work evaluated the antitumor effects of albendazole (ABZ) and its relationship with modulation of oxidative stress and induction of DNA damage. The present results showed that ABZ causes oxidative cleavage on calf-thymus DNA suggesting that this compound can break DNA. ABZ treatment decreased MCF-7 cell viability (EC50=44.9 for 24h) and inhibited MCF-7 colony formation (~67.5% at 5µM). Intracellular ROS levels increased with ABZ treatment (~123%). The antioxidant NAC is able to revert the cytotoxic effects, ROS generation and loss of mitochondrial membrane potential of MCF-7 cells treated with ABZ. Ehrlich carcinoma growth was inhibited (~32%) and survival time was elongated (~50%) in animals treated with ABZ. Oxidative biomarkers (TBARS and protein carbonyl levels) and activity of antioxidant enzymes (CAT, SOD and GR) increased, and reduced glutathione (GSH) was depleted in animals treated with ABZ, indicating an oxidative stress condition, leading to a DNA damage causing phosphorylation of histone H2A variant, H2AX, and triggering apoptosis signaling, which was confirmed by increasing Bax/Bcl-xL rate, p53 and Bax expression. We propose that ABZ induces oxidative stress promoting DNA fragmentation and triggering apoptosis and inducing cell death, making this drug a promising leader molecule for development of new antitumor drugs.

Antiproliferative effects of phenylaminonaphthoquinones are increased by ascorbate and associated with the appearance of a senescent phenotype in human bladder cancer cells.

Quinone-containing molecules have been developed against cancer mainly for their redox cycling ability leading to reactive oxygen species (ROS) formation. We have previously shown that donor-acceptor phenylaminonaphthoquinones are biologically active against a panel of cancer cells. In this report, we explored the mechanisms involved in cancer cell growth inhibition caused by two phenylaminonaphthoquinones, namely Q7 and Q9, with or without ascorbate (ASC). The results show that Q7 and Q9 are both redox cyclers able to form ROS, which strongly inhibit the proliferation of T24 cells. Q9 was a better redox cycler than Q7 because of marked stabilization of the semiquinone radical species arising from its reduction by ascorbate. Indeed, ASC dramatically enhances the inhibitory effect of Q9 on cell proliferation. Q9 plus ASC impairs the cell cycle, causing a decrease in the number of cells in the G2/M phase without involving other cell cycle regulating key proteins. Moreover, Q9 plus ASC influences the MAPK signaling pathways, provoking the appearance of a senescent cancer cell phenotype and ultimately leading to necrotic-like cell death. Because cellular senescence limits the replicative capacity of cells, our results suggest that induction of senescence may be exploited as a basis for new approaches to cancer therapy.

Inhibition of cell proliferation and migration by oxidative stress from ascorbate-driven juglone redox cycling in human bladder-derived T24 cells.

The effects of juglone on T24 cells were assessed in the presence and absence of ascorbate. The EC(50) value for juglone at 24 h decreased from 28.5 µM to 6.3 µM in the presence of ascorbate. In juglone-treated cells, ascorbate increased ROS formation (4-fold) and depleted GSH (65%). N-acetylcysteine or catalase restricted the juglone/ascorbate-mediated effects, highlighting the role of oxidative stress in juglone cytotoxicity. Juglone alone or associated with ascorbate did not cause caspase-3 activation or PARP cleavage, suggesting necrosis-like cell death. DNA damage and the mild ER stress caused by juglone were both enhanced by ascorbate. In cells treated with juglone (1-5 µM), a concentration-dependent decrease in cell proliferation was observed. Ascorbate did not impair cell proliferation but its association with juglone led to a clonogenic death state. The motility of ascorbate-treated cells was not affected. Juglone slightly restricted motility, but cells lost their ability to migrate most noticeably when treated with juglone plus ascorbate. We postulate that juglone kills cells by a necrosis-like mechanism inhibiting cell proliferation and the motility of T24 cells. These effects are enhanced in the presence of ascorbate.

Use of coal mining waste for the removal of acidity and metal ions Al (III), Fe (III) and Mn (II) in acid mine drainage.

The coal industry may generate acid mine drainage (AMD) and mining wastes, which may adversely affect the quality of the environment. In this study we propose the use of this waste in the removal of acidity and metal ions, as well as in the reduction of the toxicity of AMD. A physico-chemical analysis of the waste shows the presence of mainly SiO2, Al2O3 and Fe2O3 and a superficial area of 4.316 m2 g(-1). The treatment of AMD with the waste resulted in an increase in pH from 2.6 to 7.8 and removed 100% of the Al (III), 100% of the Fe (III) and 89% of the Mn (II). We also observed that the high toxicity of the AMD towards Daphnia magna (LC50 = 3.68%) and Artemia sp. (LC50 = 4.97%) was completely eliminated after treatment with the waste. The data obtained allow us to propose that the waste can be used in the treatment of AMD, providing an economic use for the waste.

Evaluation of remediation of coal mining wastewater by chitosan microspheres using biomarkers.

Acidic mine waters have a marked influence on the surrounding environment and pose a serious threat through long-term environmental degradation. Therefore, it is important to improve and monitor water quality with the aim of decreasing the hazard presented by this effluent emission. The aim of this work was to evaluate the remediation of mining wastewater effluents by chitosan microspheres using biomarkers of exposure and effect. DNA damage (Comet assay) and several biomarkers of oxidative stress, such as lipoperoxidation levels (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) activities, and contents of reduced glutathione (GSH), were measured in blood and liver of tilapia (Oreochromis niloticus) exposed for 7, 15, and 30 days to dechlorinated tap water, 10% coal mining wastewater (CMW), and coal mining wastewater treated with chitosan microspheres (RCM). The results indicate that hepatic TBARS levels were significantly higher in fish exposed to CMW after 7, 15, and 30 days (100%, 86%, and 63%, respectively), and after remediation there was no significant difference in relation to the control group. Hepatic GSH concentrations were lower than control values for CMW after 7 and 15 days of exposure (34% decrease at both times), and this concentration was normalized by treatment with chitosan. SOD showed increased activity in liver after 15 and 30 days of exposure, 30% and 36%, respectively, and in fish exposed to RCM there was no change in this activity compared with the control group. Increased CAT activity in liver was observed during all experimental periods in fish exposed to CMW (46%, 50%, and 56% at 7, 15, and 30 days, respectively) compared with the control or treated-water groups. The highest increase in hepatic GST activity (106%) was observed only in fish exposed to CMW for 30 days. There was an increase in DNA damage in liver (50% at 7 and 15 days) and blood (79%, 77%, and 48% at 7, 15, and 30 days, respectively) after exposure to CMW. In contrast, the fish exposed to wastewater treated with chitosan microspheres exhibited DNA fragmentation indexes similar to the control group. The results obtained indicate the use of oxidative stress biomarkers as useful tools for the toxicity evaluation of coal mining effluents and also suggest that chitosan microspheres may be used as an alternative approach for remediation of coal mining wastewaters.

Lipid lowering activity of hydrosoluble chitosan and association with Aloe vera L. and Brassica olearaceae L.

The lipid lowering activity of chitosan associated with Aloe vera L. or hydrosoluble chitosan with Brassica olearaceae L. has been studied in rats. In this study, rats were submitted to different treatments with hydrosoluble chitosan alone (4% diet), hydrosoluble chitosan associated with Aloe vera L. or hydrosoluble chitosan with Brassica olearaceae L. (1:4, 4% diet) for 35 days, to identify the formula with the highest hypolipaemic potential. The results showed that all treatments reduced blood lipid levels but that hydrosoluble chitosan associated with Brassica olearaceae L. proved most efficient, because it decreased the levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol and triglycerides in blood serum. The overall results suggest that the hydrosoluble chitosan/Brassica olearaceae L. association is a therapeutic alternative for hyperlipidaemia, and in this way may contribute to the prevention of atherogenic processes.

Time-course variations of DNA damage and biomarkers of oxidative stress in tilapia (Oreochromis niloticus) exposed to effluents from a swine industry.

DNA damage (Comet assay), lipoperoxidation levels (TBARS), and several biomarkers of oxidative stress such as catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione S-transferase (GST), and contents of reduced (GSH) and total (TG) glutathione were measured in liver and blood (Comet assay) of tilapia (Oreochromis niloticus) exposed for 7, 15, 30 (subchronic exposure), 60, and 90 days (chronic exposure) to two treatment lagoons of a swine-processing plant, the first an anaerobic lagoon and the second a final treatment lagoon. After the 15th day, TBARS increased in fish exposed to both lagoons, decreased on the 30th day, and on the 90th day remained similar to controls. Fish exposed subchronically and chronically to both effluents showed consistently greater DNA damage. The CAT and GPx activities showed similar profiles and were induced only during the first week and during the first and second months. GST activity was induced throughout the experimental period. On the other hand, GR activities showed inverted profiles, with progressively decreased activities in the liver of fish exposed to the anaerobic lagoon, and progressively increased activities in fish exposed to the final lagoon. GSH showed higher contents in liver after 60 and 90 days of exposure to the final lagoon. GSSG contents were higher in fish exposed to the final lagoon throughout the experimental period. After 15 days, tilapia exposed to both lagoons showed enhanced total glutathione contents. The hepatic antioxidant system and biomarkers of oxidative stress such as DNA fragmentation and TBARS contents of tilapia exposed to both lagoons presented biphasic profiles. These changes in the antioxidant status also indicate that the industrial treatment is not adequate to avoid damaging environmental effects.

Use of chitosan microspheres as remedial material for acidity and iron (III) contents of coal mining wastewaters.

Chitosan microspheres are highly effective in neutralizing the acidity of wastewaters from coal mining. The saturation capacity for the formation of a superficial monolayer on the adsorbent was interpreted using Langmuir isotherm and considering the amino groups as the adsorption sites for hydronium ions. The saturation capacity of the surface of the static system was 0.428 mol kg(-1), higher than that of the dynamic one. This value corresponds to the neutralization of 135 liters of wastewater per kilogram of microspheres. One gram of chitosan microspheres was capable of increasing wastewater pH from 2.5 to 4.0 and removing approximately 100% of its iron (III) contents.

Remediation of coal mining wastewaters using chitosan microspheres.

This study aimed to evaluate the potential use of chitosan and chitosan/poly(vinylalcohol) microspheres incorporating with tetrasulphonated copper (II) phthalocyanine (CTS/PVA/TCP) in the remediation of coal mining wastewaters. The process was monitored by toxicity tests both before and after adsorption treatments with chitosan and microspheres. Physicochemical parameters, including pH and trace-metal concentration, as well as bioindicators of water pollution were used to that end. Wastewater samples colleted from drainage of underground coal mines, decantation pools, and contaminated rivers were scrutinized. Acute toxicity tests were performed using the Brine Shrimp Test (BST) in order to evaluate the remediation efficiency of different treatments. The results showed that the pH of treated wastewater samples were improved to values close to neutrality. Chitosan treatments were also effective in removing trace-metals. Pre-treatment with chitosan followed by microsphere treatment (CTS/PVA/TCP) was more effective in decreasing toxicity than the treatment using only chitosan. This was probably due to the elimination of pollutants other than trace-metals. Thus, the use of chitosan and microspheres is an adequate alternative towards remediation of water pollution from coal mining.

Hypolipidaemic activity of methanol extract of Aleurites moluccana.

The lipid-lowering action of the leaves of the Aleurites moluccana methanol extract was studied in Triton W-1339 and high-fat-diet fed rats. The serum lipids (total cholesterol, LDL- and HDL-cholesterol and triglycerides) and body weight were found to be lowered by A. moluccana (300 mg/kg, b.w.) in rats with Triton-induced hypercholesterolaemia and on a hyperlipaemic diet. The results suggest that the lipid lowering action of this natural product is mediated through inhibition of hepatic cholesterol biosynthesis and reduction of lipid absorption in the intestine.

Time-dependent oxidative stress caused by benznidazole.

Benznidazole (BZN) is a nitroimidazole derivative which has a notable trypanocide activity, and it is the only drug used in Brazil and Argentina for the treatment of Chagas' disease. The drug in current use is thought to act, at least in part, by inducing oxidative stress within the parasite. Imidazolic compounds are involved in the production of reactive oxygen species (ROS). In order to evaluate the effect of BZN on ROS production and on the antioxidant status of the host, male rats were treated for different periods of time (2, 4, 6, 10 and 30 days) with 40 mg BZN/kg body weight. After treatment, biomarkers of oxidative stress such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione reductase (GR), and also thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH), total glutathione (TG) and oxidized glutathione (GSSG) concentrations, were measured in crude hepatic homogenates. Our results revealed that BZN is able to cause tissue damage as shown by increased TBARS content, inhibition of some antioxidants and induction of other antioxidants in a concentration- and time-dependent manner. The tissue damage measured as TBARS increased up to the 10th day of treatment. GST activity was inhibited during the BZN treatment. On the other hand, CAT and GR showed similar increased activities at the beginning, followed by decreased activities at the end of the treatment. After 30 days of treatment, GR activity remained low while CAT activity was high, compared to controls. The SOD activities remained unchanged throughout the experimental period. GSH showed lower values at the beginning of BZN treatment but the hepatic concentrations were enhanced at the end of the experimental period. Total glutathione showed a similar profile, and oxidized glutathione showed higher values in rats treated with BZN. In conclusion, these results indicate that, at therapeutic doses, BZN treatment elicits an oxidative stress in rat hepatocytes.

Influence of season and pollution on the antioxidant defenses of the cichlid fish acará (Geophagus brasiliensis)

The livers of Geophagus brasiliensis collected from both a non-polluted site and a polluted site were analyzed for different antioxidant defenses, O2 consumption, thiobarbituric acid-reactive substance (TBARS) levels, and histological damage. Compared to controls (116.6 + or - 26.1 nmol g-1), TBARS levels were enhanced at the polluted site (284.2 + or - 25.6 nmol g-1), as also was oxygen consumption (86.6 + or - 11.3 and 128.5 + or - 9.8 µmol O2 min-1 g-1, respectively). With respect to enzymatic antioxidants, increased catalase activities (8.7 + or - 1.3 and 29.2 + or - 2.4 mmol min-1 g-1, respectively), unchanged superoxide dismutase activities (767.2 + or - 113.3 and 563.3 + or - 70.2 U g-1, respectively), and diminished glutathione S-transferase activities (29.0 + or - 3.2 and 14.9 + or - 3.2 µmol min-1 g-1, respectively) were detected. Reduced glutathione (1.91 + or - 0.17 and 1.37 + or - 0.25 mM, respectively), oxidized glutathione (1.50 + or - 0.20 and 0.73 + or - 0.17 mM, respectively), and total glutathione (3.40 + or - 0.26 and 2.07 + or - 0.27 mM, respectively) concentrations were also below control values at the polluted site. Nevertheless, the observed ethoxyresorufin-O-deethylase activities (1.34 + or - 0.11 and 16.7 + or - 0.21 pmol min-1 mg-1, respectively) showed enhanced values at the polluted site. The main histological damage observed in the hepatocytes from fish collected at the polluted site was characterized by heavy lipid infiltration. Fish collected at the end of spring showed higher O2 consumption, higher superoxide dismutase and glutathione S-transferase activities, and higher total and oxidized glutathione concentrations compared to the beginning of autumn. No seasonal changes were observed in catalase activities, glutathione or TBARS levels. Fish chronically exposed to relatively high pollution levels seem to be unable to set up adequate antioxidant defenses, probably due to severe injury to their hepatocytes. The higher antioxidant defenses found at the end of spring are probably related to the enhanced activities during high temperature periods in thermoconforming organisms.

Influence of season and pollution on the antioxidant defenses of the cichlid fish acará (Geophagus brasiliensis).

The livers of Geophagus brasiliensis collected from both a non-polluted site and a polluted site were analyzed for different antioxidant defenses, O2 consumption, thiobarbituric acid-reactive substance (TBARS) levels, and histological damage. Compared to controls (116.6 +/- 26.1 nmol g-1), TBARS levels were enhanced at the polluted site (284.2 +/- 25.6 nmol g-1), as also was oxygen consumption (86.6 +/- 11.3 and 128.5 +/- 9.8 micromol O2 min-1 g-1, respectively). With respect to enzymatic antioxidants, increased catalase activities (8.7 +/- 1.3 and 29.2 +/- 2.4 mmol min-1 g-1, respectively), unchanged superoxide dismutase activities (767.2 +/- 113.3 and 563.3 +/- 70.2 U g-1, respectively), and diminished glutathione S-transferase activities (29.0 +/- 3.2 and 14.9 +/- 3.2 micromol min-1 g-1, respectively) were detected. Reduced glutathione (1.91 +/- 0.17 and 1.37 +/- 0.25 mM, respectively), oxidized glutathione (1.50 +/- 0.20 and 0.73 +/- 0.17 mM, respectively), and total glutathione (3.40 +/- 0.26 and 2.07 +/- 0.27 mM, respectively) concentrations were also below control values at the polluted site. Nevertheless, the observed ethoxyresorufin-O-deethylase activities (1.34 +/- 0.11 and 16.7 +/- 0.21 pmol min-1 mg-1, respectively) showed enhanced values at the polluted site. The main histological damage observed in the hepatocytes from fish collected at the polluted site was characterized by heavy lipid infiltration. Fish collected at the end of spring showed higher O2 consumption, higher superoxide dismutase and glutathione S-transferase activities, and higher total and oxidized glutathione concentrations compared to the beginning of autumn. No seasonal changes were observed in catalase activities, glutathione or TBARS levels. Fish chronically exposed to relatively high pollution levels seem to be unable to set up adequate antioxidant defenses, probably due to severe injury to their hepatocytes. The higher antioxidant defenses found at the end of spring are probably related to the enhanced activities during high temperature periods in thermoconforming organisms.

Sera from chronic chagasic patients depress cardiac electrogenesis and conduction.

We report results obtained with sera from 58 chronic chagasic patients that were evaluated for effects on heart rate and atrioventricular (AV) conduction in isolated rabbit hearts and screened for the presence of muscarinic and beta-adrenergic activity. We show that sera from 26 patients decreased heart rate, while 10 increased it and 22 had no effect. Additionally, sera from 20 of the 58 patients blocked AV conduction. Muscarinic activation seems to be involved in both effects, but is not the only mechanism, since atropine did not antagonize the decrease in heart rate in 23% of sera or AV block in 40%. Sera from patients with complex arrhythmias were significantly more effective in depressing both heart rate and AV conduction. Sera that induce increases in heart rate seem to operate exclusively through beta-adrenergic activation. Two of these sera, evaluated with respect to intercellular communication in primary cultures of embryonic cardiomyocytes were able to block gap junction conductance evaluated by a dye injection technique after 24-h exposure. The mechanisms underlying this uncoupling effect are currently being investigated.

Sera from chronic chagasic patients depress cardiac electrogenesis and conduction

We report results obtained with sera from 58 chronic chagasic patients that were evaluated for effects on heart rate and atrioventricular (AV) conduction in isolated rabbit hearts and screened for the presence of muscarinic and beta-adrenergic activity. We show that sera from 26 patients decreased heart rate, while 10 increased it and 22 had no effect. Additionally, sera from 20 of the 58 patients blocked AV conduction. Muscarinic activation seems to be involved in both effects, but is not the only mechanism, since atropine did not antagonize the decrease in heart rate in 23 percent of sera or AV block in 40 percent. Sera from patients with complex arrhythmias were significantly more effective in depressing both heart rate and AV conduction. Sera that induce increases in heart rate seem to operate exclusively through beta-adrenergic activation. Two of these sera, evaluated with respect to intercellular communication in primary cultures of embryonic cardiomyocytes were able to block gap junction conductance evaluated by a dye injection technique after 24-h exposure. The mechanisms underlying this uncoupling effect are currently being investigated

Gas exchange during exercise in different evolutional stages of chronic Chagas' heart disease.

OBJECTIVE: To compare gas exchange at rest and during exercise in patients with chronic Chagas' heart disease grouped according to the Los Andes clinical hemodynamic classification. METHODS: We studied 15 healthy volunteers and 52 patients grouped according to the Los Andes clinical and hemodynamic classification as follows: 17 patients in group IA (normal electrocardiogram and echocardiogram), 9 patients in group IB (normal electrocardiogram and abnormal echocardiogram), 14 patients in group II (abnormal electrocardiogram and echocardiogram, without congestive heart failure), and 12 patients in group III (abnormal electrocardiogram and echocardiogram with congestive heart failure). The following variables were analyzed: oxygen consumption (V O2), carbon dioxide production (V CO2), gas exchange rate (R), inspiratory current volume (V IC), expiratory current volume (V EC), respiratory frequency, minute volume (V E), heart rate (HR), maximum load, O2 pulse, and ventilatory anaerobic threshold (AT). RESULTS: When compared with the healthy group, patients in groups II and III showed significant changes in the following variables: V O2 peak, V CO2 peak, V IC peak, V EC peak, E, HR, and maximum load. Group IA showed significantly better results for these same variables as compared with group III. CONCLUSION: The functional capacity of patients in the initial phase of chronic Chagas' heart disease is higher than that of patients in an advanced phase and shows a decrease that follows the loss in cardiac-hemodynamic performance.

Presence of antibodies against the third intracellular loop of the m2 muscarinic receptor in the sera of chronic chagasic patients.

Patients in the chronic phase of Chagas' disease suffer from a slowly evolving inflammatory cardiomyopathy that can lead to severe cardiac dilatation, congestive heart failure, and death. This process appears to be caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate decades after infection with the parasite Trypanosoma cruzi. Recent evidence suggests that there are circulating antibodies in chronic chagasic patients that alter the physiological behavior of the heart on binding to G-protein-coupled cardiovascular receptors, including beta1-adrenergic and m2 muscarinic receptors. A 42 kDa fusion protein was constructed that contains the central part of the third intracellular loop (i3; Arg(267)-Arg(381)) of the human m2 muscarinic receptor, linked to glutathione S-transferase. This fusion protein was overexpressed in Escherichia coli and subsequently purified by affinity chromatography. Based on Western blots, the i3 loop is specifically recognized by the sera of chronic chagasic patients who have reached advanced stages of cardiac failure (according to the Los Andes classification). Analysis of the prevalence and distribution of these antibodies shows a strong association between seropositive patients and moderate (group II) to severe (group III) heart dysfunction.

Saliva ELISA: a method for the diagnosis of chronic Chagas disease in endemic areas.

An indirect enzyme linked immunosorbent assay (ELISA) was applied to saliva to detect chronic infection by Trypanosoma cruzi in humans. Saliva samples from 114 Chagas' disease chronically infected individuals, characterized by three serological tests and clinical evaluation and from 100 healthy controls were tested for T. cruzi specific IgG antibodies. At dilution of 1 in 2, specific antibodies were detected in saliva samples from 103 of 114 samples from infected patients and 5 of 100 controls (sensitivity 90.4%, specificity 95%). There was no significant correlation between the antibody titre and cardiac or gastrointestinal tract disease. This assay possesses some advantages over other methods as saliva collection is non-invasive, requires no special equipment and whole saliva gave reproducible results. Although serology remains the gold standard for T. cruzi infection, these results suggest that T. cruzi specific salivary antibody detection may provide a screening diagnostic test and contribute to epidemiological studies of chronic trypanosomiasis infection in endemic areas.

Functionally active cardiac antibodies in chronic Chagas' disease are specifically blocked by Trypanosoma cruzi antigens.

Antibodies of chronic chagasic patients have been shown to interfere with electric and mechanical activities of cardiac embryonic myocytes in culture and with whole mammalian hearts. A mechanism proposed for this effect involves interaction of the antibodies with G-protein-linked membrane receptors, thus leading to activation of beta adrenergic and muscarinic receptors; more specifically, IgG of chagasic patients would interact with the negatively charged regions of the second extracellular loop of these receptors. We performed competition experiments to test this hypothesis. We evaluated the effect of sera/IgG from patients previously known to depress electrogenesis and/or atrioventricular conduction in isolated rabbit hearts after incubation with live and lysed parasites, the peptide corresponding to the second extracellular loop (O2) of the M2 receptor, and different peptides derived from two ribosomal proteins of T. cruzi: P0 and P2beta. Our results indicate that 1) the antigenic factor inducing the functionally active IgGs in the chagasic patients is probably an intracellular T. cruzi antigen; 2) IgG/serum is interacting with the O2 region of the M2 receptor in the rabbit heart; and 3) the negative charges present in the ribosomal proteins of T. cruzi are important in mediating the interaction between the patients' serum/IgG and the receptor.

Sera from chronic chagasic patients with complex cardiac arrhythmias depress electrogenesis and conduction in isolated rabbit hearts.

BACKGROUND: Immune dysfunction has long been proposed as a mechanism for the etiopathogenesis of the chronic phase of Chagas' disease. Antibodies of chagasic patients have been shown to interfere with electric and mechanical activity of embryonic myocardial cells in culture. Here, we demonstrate that antibodies derived from a group of chronic chagasic patients are able to induce disturbances in the electrogenesis and conduction in isolated adult rabbit hearts. METHODS AND RESULTS: Sera from chronic chagasic patients with complex cardiac arrhythmias (ChA+) decreased heart rate (from 131+/-26 to 98+/-37 bpm [mean+/-SD]; n=6; P<.05) in isolated rabbit hearts when perfused at a dilution of 1:100 (vol:vol) by the Langendorff method. Sera from another experimental group of four chronic chagasic patients without complex arrhythmias (ChA-) and two control groups composed of five Wolff-Parkinson-White (WPW) syndrome patients and five orthopedic surgery patients did not affect heart rate when tested under similar conditions. In addition, sera from five of six ChA+ patients and from one WPW patient induced AV conduction blockade. Effects of the sera from ChA+ patients are due to their IgG fractions. Both serum and IgG effects are blocked by atropine (10 micromol/L). CONCLUSIONS: Antibodies of ChA+ patients decrease heart rate and induce AV conduction block in isolated adult rabbit hearts through activation of muscarinic receptors.