Toxicogenetic profile of the monoterpene alpha-terpineol on normal and tumor eukaryotic cells.

Alpha-terpineol is a monoterpene alcohol found in essential oils from medicinal plants with some well-known pharmacological activities and widely used in cosmetics. However, the toxicological effects and additional pharmacological activities need to be clarified. Thus, the study evaluated the toxic, cytotoxic, genotoxic, hemolytic, and oxidative potential of alpha-terpineol in non-clinical bioassays. Different concentrations of alpha-terpineol were used in bioassays, including MTT (50, 100, 200, and 400 µg/mL), Artemia salina (6.25-400 µg/mL), Allium cepa (10, 50, and 100 µg/mL), comet assay (100, 200, and 500 µg/mL), cytokinesis-block micronucleus (100, 250, and 500 µg/mL), confocal microscopy for apoptosis quantification (100 and 500 µg/mL), hemolysis and Saccharomyces cerevisiae central disk test (10, 35, and 75 µg/mL). For the MTT test, alpha-terpineol was more cytotoxic on melanoma murine B16-F10 cells rather than macrophages. For A. salina test, alpha-terpineol showed LC50 of 68.29 and 76.36 µg/mL for 24 h and 48 h of exposure time, respectively. Meanwhile, alpha-terpineol was also cytotoxic to meristematic cells, which revealed inhibition of cellular division and mutagenic action by formation of bridges and delayed anaphases. The compound increased damage index and frequency of damage corroborated by the presence of micronuclei, bridges and nuclear buds at 500 µg/mL, but it caused neither hemolysis, oxidative damage on the S. cerevisiae nor cell death in normal fibroblasts. The findings indicate alpha-terpineol has cytotoxic potential by cytogenetic and molecular mechanisms associated with apoptosis and probable target effects against melanoma cells.

Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages.

We have previously described that arachidonic acid (AA)-5-lipoxygenase (5-LO) metabolism inhibitors such as NDGA and MK886, inhibit cell death by apoptosis, but not by necrosis, induced by extracellular ATP (ATPe) binding to P2X7 receptors in macrophages. ATPe binding to P2X7 also induces large cationic and anionic organic molecules uptake in these cells, a process that involves at least two distinct transport mechanisms: one for cations and another for anions. Here we show that inhibitors of the AA-5-LO pathway do not inhibit P2X7 receptors, as judged by the maintenance of the ATPe-induced uptake of fluorescent anionic dyes. In addition, we describe two new transport phenomena induced by these inhibitors in macrophages: a cation-selective uptake of fluorescent dyes and the release of ATP. The cation uptake requires secreted ATPe, but, differently from the P2X7/ATPe-induced phenomena, it is also present in macrophages derived from mice deficient in the P2X7 gene. Inhibitors of phospholipase A2 and of the AA-cyclooxygenase pathway did not induce the cation uptake. The uptake of non-organic cations was investigated by measuring the free intracellular Ca(2+) concentration ([Ca(2+)]i) by Fura-2 fluorescence. NDGA, but not MK886, induced an increase in [Ca(2+)]i. Chelating Ca(2+) ions in the extracellular medium suppressed the intracellular Ca(2+) signal without interfering in the uptake of cationic dyes. We conclude that inhibitors of the AA-5-LO pathway do not block P2X7 receptors, trigger the release of ATP, and induce an ATP-dependent uptake of organic cations by a Ca(2+)- and P2X7-independent transport mechanism in macrophages.

Analysis of SIKVAV's receptor affinity, pharmacokinetics, and pharmacological characteristics: a matrikine with potent biological function.

Matrikines are biologically active peptides generated from fragments fragmentation of extracellular matrix components (ECM) that are functionally distinct from the original full-length molecule. The active matricryptic sites can be unmasked by ECM components enzymatic degradation or multimerization, heterotypic binding, adsorption to other molecules, cell-mediated mechanical forces, exposure to reactive oxygen species, ECM denaturation, and others. Laminin α1-derived peptide (SIKVAV) is a bioactive peptide derived from laminin-111 that participates in tumor development, cell proliferation, angiogenesis in various cell types. SIKVAV has also a potential pharmaceutical activity that may be used for tissue regeneration and bioengineering in Alzheimer's disease and muscular dystrophies. In this work, we made computational analyzes of SIKVAV regarding the ADMET panel, that stands for Administration, Distribution, Metabolism, Excretion, and Toxicity. Docking analyzes using the α3ß1 and α6ß1 integrin receptors were performed to fill in the gaps in the SIKVAV's signaling pathway and coupling tests showed that SIKVAV can interact with both receptors. Moreover, there is no indication of cytotoxicity, mutagenic or carcinogenic activity, skin or oral sensitivity. Our analysis suggests that SIKVAV has a high probability of interacting with peroxisome proliferator-activated receptor-gamma (NR-PPAR-γ), which has anti-inflammatory activity. The results of bioinformatics can help understand the participation of SIKVAV in homeostasis and influence the understanding of how this peptide can act as a biological asset in the control of dystrophies, neurodegenerative diseases, and tissue engineering.Communicated by Ramaswamy H. Sarma.

Promising Effects of Casearins in Tumor-Bearing Mice and Antinociceptive Action against Oncologic Pain: Molecular Docking and In Vivo Findings.

Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12-39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.

Films composed of white angico gum and chitosan containing chlorhexidine as an antimicrobial agent.

Anadenanthera colubrina, popularly known as white angico, is a species extensively cultivated in Brazil, mainly in the cerrado region, including the state of Piauí. This study examines the development of films composed of white angico gum (WAG) and chitosan (CHI) and containing chlorhexidine (CHX), an antimicrobial agent. The solvent casting method was used to prepare films. Different combinations and concentrations of WAG and CHI were used to obtain films with good physicochemical characteristics. Properties such as the in vitro swelling ratio, the disintegration time, folding endurance, and the drug content were determined. The selected formulations were characterised by scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and X-ray diffraction, and the CHX release time and antimicrobial activity were evaluated. CHX showed a homogenous distribution in all CHI/WAG film formulations. The optimised films showed good physicochemical properties with 80% CHX release over 26 h, which is considered promising for local treatment of severe lesions in the mouth. Cytotoxicity tests of the films did not show toxicity. The antimicrobial and antifungal effects were very effective against the tested microorganisms.

Toxic profile of marinobufagin from poisonous Amazon toads and antitumoral effects on human colorectal carcinomas.

ETHNOPHARMACOLOGICAL RELEVANCE: South Americans natives have extensively used the toad "kururu" to reduce/treat skin infections, cutaneous lesions and sores. They release secretions rich in bufadienolides, polyhydroxy steroids with well-documented cardiotonic and antiproliferative actions, but in vivo antitumoral evaluations in mammals are rare, and toxicological safety has been left in second place. AIMS OF THE STUDY: This investigation used in silico, in vitro and in vivo tools to evaluate acute and subacute toxic effects of marinobufagin and the anticancer action in tumor-bearing mice models. MATERIALS AND METHODS: Initially, in silico toxic predictions were performed, followed by in vitro assays using human and murine normal and tumor lines. Next, acute and subacute studies on mice investigated the behavior, hematological and intestinal transit profile and antitumoral activity of marinobufagin in sarcoma 180- and HCT-116 colorectal carcinoma-transplanted mice for 7 and 15 days, respectively. Ex vivo and in vivo cytogenetic assays in Sarcoma 180 and bone marrow cells and histopathological examinations were also executed. RESULTS: In silico studies revealed ecotoxicological effects on crustaceans (Daphnia sp.), fishes (Pimephales promelas and Oryzias latipes), and algae. A 24-h marinobufagin-induced acute toxicity included signals of central activity, mainly (vocal frenzy, absence of body tonus, increased ventilation, ataxia, and equilibrium loss), and convulsions and death at 10 mg/kg. The bufadienolide presented effective in vitro cytotoxic action on human lines of colorectal carcinomas in a similar way to ouabain and tumor reduction in marinobufagin-treated SCID-bearing HCT-116 heterotopic xenografts. Animals under subacute nonlethal doses exhibited a decrease in creatinine clearance with normal levels of blood urea, probably as a result of a marinobufagin-induced renal perfusion fall. Nevertheless, only minor morphological side effects were identified in kidneys, livers, hearts and lungs. CONCLUSIONS: Marinobufagin has in vitro and in vivo anticancer action on colorectal carcinoma and mild and reversible alterations in key metabolic organs without direct chemotherapy-induced gastrointestinal effects at subacute exposure, but it causes acute ataxia, equilibrium loss, convulsions and death at higher acute exposure.

Antiulcerogenic and Antibacterial Effects of Chitosan Derivatives on Experimental Gastric Ulcers in Rats.

Gastric ulcer is an injury that develops on the lining of the stomach due to an imbalance between aggressive and defensive agents. Chitosan derivatives demonstrate promising biological activities in accelerating the healing activity of gastric lesions. Thus, this study aimed at investigating the healing activity of gastric lesion, induced by acetic acid (80%), of the chitosan derivative with acetylacetone (Cac) modified with ethylenediamine (Cacen) or diethylenetriamine (Cacdien). The biological activity was determined based on cytotoxicity, antibacterial activity, and gastroprotective activities. The results showed no significant difference in the cytotoxicity, a better antibacterial activity against S. aureus and E. coli, and a positive result on the healing of gastric lesions of the materials (Cac 18.4%, Cacen 55.2%, and Cacdien 68.1%) compared to pure chitosan (50.7%). Therefore, the results indicate that derivatives of chitosan are promising biomaterials for application in the control of lesions on the gastric mucosa.

Anti-Leishmania activity of extracts from Piper cabralanum C.DC. (Piperaceae).

Species of Piperaceae are known by biological properties, including antiparasitic such as leishmanicidal, antimalarial and in the treatment of schistosomiasis. The aim of this work was to evaluate the antileishmania activity, cytotoxic effect, and macrophage activation patterns of the methanol (MeOH), hexane (HEX), dichloromethane (DCM) and ethyl acetate (EtOAc) extract fractions from the leaves of Piper cabralanum C.DC. The MeOH, HEX and DCM fractions inhibited Leishmanina amazonensis promastigote-like forms growth with a half maximal inhibitory concentration (IC50) of 144.54, 59.92, and 64.87 µg/mL, respectively. The EtOAc fraction did not show any relevant activity. The half maximal cytotoxic concentration (CC50) for macrophages were determined as 370.70, 83.99, 113.68 and 607 µg/mL for the MeOH, HEX and DCM fractions, respectively. The macrophage infectivity was concentration-dependent, especially for HEX and DCM. MeOH, HEX and DCM fractions showed activity against L. amazonensis with low cytotoxicity to murine macrophages and lowering infectivity by the parasite. Our results provide support for in vivo studies related to a potential application of P. cabralanum extract and fractions as a promising natural resource in the treatment of leishmaniasis.

Computational analysis of eugenol inhibitory activity in lipoxygenase and cyclooxygenase pathways.

Chronic inflammation is triggered by numerous diseases such as osteoarthritis, Crohn's disease and cancer. The control of the pro-inflammatory process can prevent, mitigate and/or inhibit the evolution of these diseases. Therefore, anti-inflammatory drugs have been studied as possible compounds to act in these diseases. This paper proposes a computational analysis of eugenol in relation to aspirin and diclofenac and analyzing the ADMET profile and interactions with COX-2 and 5-LOX enzymes, important enzymes in the signaling pathway of pro-inflammatory processes. Through the analysis of ADMET in silico, it was found that the pharmacokinetic results of eugenol are similar to NSAIDs, such as diclofenac and aspirin. Bioinformatics analysis using coupling tests showed that eugenol can bind to COX-2 and 5-LOX. These results corroborate with different findings in the literature that demonstrate anti-inflammatory activity with less gastric irritation, bleeding and ulcerogenic side effects of eugenol. The results of bioinformatics reinforce studies that try to propose eugenol as an anti-inflammatory compound that can act in the COX-2/5-LOX pathways, replacing some NSAIDs in different diseases.

preADMET analysis and clinical aspects of dogs treated with the Organotellurium compound RF07: A possible control for canine visceral leishmaniasis?

Tellurium compounds have been described as potential leishmanicides, bearing promising leishmanicidal and antimalarial effects. Therefore, the present study investigated the pharmacological potential of the organotellurane compound RF07 through preADMET parameters, such as absorption, distribution, metabolism and excretion. After studying the pharmacokinetic properties of RF07, studies were carried out on dogs naturally infected with visceral leishmaniasis after the administration of RF07, in order to assess pathophysiological parameters. Thus, dogs were divided into 4 groups with administration of daily intraperitoneal injections for 3 weeks (containing RF07 or placebo). During the trial, hematological parameters, renal and hepatic toxicity were evaluated. Serum urea, creatinine, alkaline phosphatase, transaminases (GOT and GPT), as well as hemogram results, were evaluated before the first administration and during the second and third weeks after the start of the treatment. In dogs with VL, RF07 improved liver damage, regulated GPT levels and significantly decreased leukocyte count, promoting its regularization. These phenomena occurred at the end of the third week of treatment. The administration of RF07 promoted a significant decrease in the average levels of GOT and GPT after the third week of treatment and did not significantly alter the hematological parameters. The application of RF07 in the treatment of visceral leishmaniasis suggests that it is an alternative to the disease, since the reversal of clinical signs in dogs with VL requires the use of 0.6 mg/kg.

Assessment of In Vitro Anti-melanoma Potential of Ephedranthus pisocarpus R.E.Fr.

BACKGROUND/AIM: Despite being a rare disease, melanoma is considered the most dangerous skin cancer due to its highly invasive and aggressive nature, and still requires for more effective treatments. The aim of this study was to evaluate the in vitro anti-melanoma potential of Ephedranthus pisocarpus R.E.Fr. (Annonaceae), a popular Brazilian plant with medicinal properties. MATERIALS AND METHODS: Initially, the ethanolic extract (EtOH) was obtained from E. pisocarpus leaves and later partitioned using increasing polarity solvents. The anti-melanoma potential of E. pisocarpus was assessed by spectrophotometry and its cytotoxicity determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and confocal microscopy. RESULTS: We demonstrated that the EtOH extract and fractions from E. pisocarpus had a moderate photoprotective action (FPS 3.0-5.0) against UVA radiation. Interestingly, the dichloromethane fraction presented higher anti-melanoma activity against B16-F10 (IC50=46.8 µg/ml) and SK-MEL-28 cells (IC50=40.1 µg/ml) and lesser toxicity on normal cells. Additionally, our study reported that spathulenol, one of the major constituents from E. pisocarpus, acts through an apoptosis-dependent mechanism in SK-MEL-28 cells. CONCLUSION: The present study demonstrated, for the first time, the in vitro anti-melanoma potential of E. pisocarpus against melanoma cells.

ATP-induced apoptosis involves a Ca2+-independent phospholipase A2 and 5-lipoxygenase in macrophages.

Macrophages express P2X(7) and other nucleotide (P2) receptors, and display the phenomena of extracellular ATP (ATP(e))-induced P2X(7)-dependent membrane permeabilization and cell death by apoptosis and necrosis. P2X(7) receptors also cooperate with toll-like receptors (TLRs) to induce inflammasome activation and IL-1beta secretion. We investigated signaling pathways involved in the induction of cell death by ATP(e) in intraperitoneal murine macrophages. Apoptosis (hypodiploid nuclei) and necrosis (LDH release) were detected 6h after an induction period of 20 min in the presence of ATP. Apoptosis was blocked by caspase 3 and caspase 9 inhibitors and by cyclosporin A. The MAPK inhibitors PD-98059, SB-203580 and SB-202190 provoked no significant effect on apoptosis, but SB-203580 blocked LDH release. Neither apoptosis nor necrosis was inhibited when both intra- and extracellular Ca(2+) were chelated during the induction period. Mepacrine, a generic PLA(2) inhibitor and BEL, an inhibitor of Ca(2+)-independent PLA(2) (iPLA(2)) blocked apoptosis, while pBPB and AACOOPF(3), inhibitors of secretory and Ca(2+)-dependent PLA(2) respectively, had no significant effect. Cycloxygenase inhibitors had no effect on apoptosis, while the inhibitors of lipoxygenase (LOX) and leukotriene biosynthesis nordihydroguaiaretic acid (NDGA), zileuton, AA-861, and MK-886 significantly decreased apoptosis. Neither NDGA nor MK-886 blocked apoptosis of 5-LOX(-/-) macrophages. CP-105696 and MK-571, antagonists of leukotriene receptors, had no significant effect on apoptosis. None of the inhibitors of PLA(2) and LOX/leukotriene pathway had a significant inhibitory effect on LDH release. Our results indicate that a Ca(2+)-independent step involving an iPLA(2) and 5-LOX are involved in the triggering of apoptosis but not necrosis by P2X(7) in macrophages.

Effects of pesticides on rural workers: haematological parameters and symptomalogical reports.

Exposure to pesticides by the rural population is increasing worldwide. Pesticides can induce the development of different diseases such as cancer and diseases of the central nervous system. This study analysed the clinical symptoms and haematological changes of a rural population in Conceição do Castelo, Espirito Santo, Brazil. For evaluation of symptomatology exposure to pesticides, 142 rural workers were interviewed. Of these, 22 workers were selected for haematological tests randomly as to evaluate haematological changes during the period of exposure to pesticides. Haematological analyses showed that erythrocytes, haemoglobin, haematocrit, mean corpuscular (VCM) volume, mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) are in accordance with the reference intervals in haematology. Variations in the concentrations of rods and neutrophils indicates that exposure to pesticides increases the amount of those cells. Haematological disorders in rural workers exposed to pesticides can be correlated with reported symptoms. The results described in this study are relevant to the health public and reinforce the concern about the indiscriminate use of pesticides.

Biological properties of chitosan derivatives associated with the ceftazidime drug.

Chitosan has become promising as a biomaterial because of its biocompatible, biodegradable nature and non-toxic. The biochemical and antioxidant properties of chitosan modified with acetylacetone and ethylenediamine (Cacen) or diethylenetriamine (Cacdien) associated with ceftazidime (F) were investigated. Chitosan was characterized using Elemental Analysis (CHN), Thermal Analysis (TG/DTG/DSC), X-Ray Diffractometry (XRD), and was investigated an in vitro hemolytic cytotoxicity test, Artemia saline larvae for toxicity and in vitro antioxidant activity by DPPH (2,2-diphenyl-1-picrylhydrazyl). The chemical modification was confirmed by CHN, XRD and TG. The Cacen, Cacdien, CacenF and CacdienF derivatives presented high percentages of nitrogen (7.6%, 7.9%, 14.1% and 19.2%, respectively), confirming the modification and drug adsorption. The average molecular weight of chitosan and its derivatives were 132 kDa, with very few variations after modification. This incorporation decreased in the crystallinity index of Cacen (7.1%) and Cacdien (4.3%), as well as the incorporation of the drug (CacenF 0.3% and CacdienF 3.4%). FTIR spectra showed bands at 1580-1654 cm-1 referring to carbonyl and imine group and bands at 3500-3300 and 1462-1264 cm-1 related to vibration and deformation the amine group. 13C NMR spectroscopy was observed new peaks in carbonyl and imine regions (170-200 ppm). The thermal stability of the derivatives without the drug improved according to TG/DTG/DSC analysis, however there were decreased in the derivatives with the drug. The biocompatibility of the derivatives was confirmed by the low hemolytic rate (<5%), non-toxic on Artemia salina (LD50%>3000 ppm), and significant index (1-34%) of antioxidant activity. The results demonstrated that chitosan and its derivatives are promising biomaterials.

Retinol palmitate and ascorbic acid: Role in oncological prevention and therapy.

Cancer development has been directly related to oxidative stress. During chemotherapy, some cancer patients use dietary antioxidants to avoid nutritional deficiencies due to cancer treatment. Among the antioxidants consumed, there are vitamins, including retinyl palmitate (PR) and ascorbic acid (AA), which have the capacity to reduce free radicals formation, protect cellular structures and maintain the cellular homeostasis. This systematic review evaluated the antioxidant and antitumor mechanisms of retinol palmitate (a derivative of vitamin A) and/or ascorbic acid (vitamin C) in cancer-related studies. Ninety-seven (97) indexed articles in the databases PubMed and Science Direct, published between 2013 and 2017, including 23 clinical studies (5 for every single compound while 13 in interaction) and 74 non-clinical studies (37 for retinol palmitate, 36 for ascorbic acid and 1 in interaction) were considered. Antioxidant and antitumor effects, with controversies over dosage and route of administration, were observed for the test compounds in their isolated form or associated in clinical studies. Prevention of cancer risks against oxidative damage was seen in lower doses of retinol palmitate and/or vitamin C. However, at high doses, they can generate reactive oxygen species, cytotoxicity and apoptosis in test systems. Non-clinical studies using cell lines have allowed understanding the mechanisms related to antioxidants and antitumor effects of the isolated compounds, however, studies on vitamin interactions, acting as antioxidants and/or antitumor are still rare and controversial. More studies, mainly related to modulation of antineoplastic drugs are needed for understanding the risks and benefits of their use during treatment in order to achieve effectiveness in cancer therapy and patient's quality of life.

Encapsulation of Piper cabralanum (Piperaceae) nonpolar extract in poly(methyl methacrylate) by miniemulsion and evaluation of increase in the effectiveness of antileukemic activity in K562 cells.

This study aimed to synthesize and characterize nanoparticles (NPs) of poly(methyl methacrylate) (PMMA) and evaluate their ability to incorporate plant extracts with antitumor activity and low dissolution in aqueous media. The extract used was n-hexane partition of the methanol extract of Piper cabralanum (PCA-HEX). PMMA NPs were obtained using the mini-emulsion method, which was able to encapsulate almost 100% of PCA-HEX. The synthesized polymeric particles presented with a size of 200 nm and a negative charge. Cytotoxicity tests by MTT and trypan blue assays showed that NPs without PCA-HEX did not kill leukemic cells (K562 cells). NPs containing PCA-HEX were able to enhance cell death when compared to pure extract. The results showed that PMMA NPs could be useful as a drug delivery system as they can enhance the antitumor activity of the PCA-HEX extract by more than 20-fold. PMMA NPs containing plant extracts with antitumor activities may be an alternative to control the evolution of diseases such as leukemia.

Effects of pesticides on rural workers: haematological parameters and symptomalogical reports / Efeitos dos pesticidas sobre trabalhadores rurais: parâmetros hematológicos e relatos sintomatológicos

Abstract Exposure to pesticides by the rural population is increasing worldwide. Pesticides can induce the development of different diseases such as cancer and diseases of the central nervous system. This study analysed the clinical symptoms and haematological changes of a rural population in Conceição do Castelo, Espirito Santo, Brazil. For evaluation of symptomatology exposure to pesticides, 142 rural workers were interviewed. Of these, 22 workers were selected for haematological tests randomly as to evaluate haematological changes during the period of exposure to pesticides. Haematological analyses showed that erythrocytes, haemoglobin, haematocrit, mean corpuscular (VCM) volume, mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) are in accordance with the reference intervals in haematology. Variations in the concentrations of rods and neutrophils indicates that exposure to pesticides increases the amount of those cells. Haematological disorders in rural workers exposed to pesticides can be correlated with reported symptoms. The results described in this study are relevant to the health public and reinforce the concern about the indiscriminate use of pesticides.

Resumo A exposição a pesticidas pela população rural está crescendo em todo o mundo. Os pesticidas podem induzir o desenvolvimento de diferentes doenças, como o cancer e as do sistema nervoso central. Este estudo analisou os sintomas clínicos e alterações hematológicas de uma população rural em Conceição do Castelo, Espírito Santo, Brasil. Para a avaliação da exposição a pesticidas e sintomatologias, 142 trabalhadores rurais foram entrevistados. Destes, 22 trabalhadores foram selecionados de randomicamente para testes hematológicos e avaliação de alterações hematológicas durante o período de exposição a pesticidas. Análises hematológicas mostraram que eritrócitos, hemoglobina, hematócrito, volume corpuscular médio (VCM), hemoglobina corpuscular média (HCM), concentração de hemoglobina corpuscular média (CHCM) estão em conformidade com os intervalos de referência. As variações nas concentrações de bastonetes e neutrófilos indicam que a exposição a pesticidas aumenta a quantidade dessas células. Alterações hematológicas em trabalhadores rurais expostos a pesticidas podem ser correlacionados com alguns sintomas relatados. Os resultados descritos neste estudo são relevantes para a saúde pública e para reforçar a preocupação com o uso indiscriminado de pesticidas.