RESUMEN
O descarte inadequado de medicamentos pode levar a impactos ambientais negativos e deve ser considerado um problema de saúde pública. O presente estudo teve como objetivo levantar dados quantitativos e qualitativos relacionados ao perfil dos medicamentos descartados no município de Governador Valadares - MG. O trabalho foi desenvolvido nas UAPS/ESF que possuíam farmácias, e também na Farmácia Central/Policlínica Municipal. Nesses locais, foi realizada uma análise dos medicamentos descartados no período de julho de 2017 a maio de 2018. Por meio dos dados obtidos nesse período foi possível perceber que as principais classes de medicamentos descartadas foram os inibidores da enzima conversora de angiotensina, antagonistas da angiotensina II, agentes betabloqueadores, diuréticos, hipoglicemiantes, contraceptivos hormonais e agentes modificadores de lipídeos. Além disso, foi realizada uma ação de educação em saúde e aplicado um questionário semiestruturado aos usuários participantes dos grupos operativos. Dos 34 usuários respondentes do questionário, 23 (69,70%) não tinham acesso a informação sobre o local correto de descarte e armazenamento de medicamentos. Após a ação de educação em saúde verificou-se um aumento no quantitativo de medicamentos descartados pelos usuários nas UAPS/ESF Mãe de Deus I e II, Altinópolis III e IV, Santa Rita II, São Pedro I e II e Esperança e Nossa Senhora das Graças. O trabalho desenvolvido permitiu apresentar dados relevantes para a gestão municipal demonstrando a importância do farmacêutico no cuidado em saúde e o caráter epidemiológico local da prevalência das doenças crônico não transmissíveis.
The inadequate disposal of drugs can lead to negative environmental impacts and should be treated as a public health problem. This study aimed at surveying quantitative and qualitative data related to the profile of drugs discarded in the city of Governador Valadares - MG. The work was developed in the UAPS / ESF that had pharmacies, and also in the Central Pharmacy/Municipal Polyclinic. In these locations, an analysis of the drugs discarded between July 2017 and May 2018 was carried out. Through the data obtained in this period, it was possible to notice that the main classes of drugs discarded were angiotensin-converting enzyme inhibitors, angiotensin II antagonists, beta-blocking agents, diuretics, hypoglycemic agents, hormonal contraceptives, and lipid-modifying agents. In addition, a health education action was carried out and a semi-structured questionnaire was applied to users participating in the operating groups. From the 34 users who responded the questionnaire, 23 (69.70%) did not have access to information on the correct place to dispose and store medicines. After the health education action, there was an increase in the amount of drugs discarded by users in the UAPS/ESF Mãe de Deus I and II, Altinópolis III and IV, Santa Rita II, São Pedro I and II, and Esperança and Nossa Senhora das Graças. The work carried out made it possible to present relevant data for municipal management, demonstrating the importance of the pharmacist in health care and the local epidemiological character of the prevalence of chronic non-communicable diseases.
Asunto(s)
Humanos , Masculino , Femenino , Farmacias/provisión & distribución , Preparaciones Farmacéuticas , Pacientes , Farmacéuticos/provisión & distribución , Comprimidos/provisión & distribución , Inhibidores de la Enzima Convertidora de Angiotensina/provisión & distribución , Centros de Salud , Salud Pública/educación , Educación en Salud , Administración Municipal/legislación & jurisprudencia , Atención a la Salud , Diabetes Mellitus/tratamiento farmacológico , Almacenaje de Medicamentos , Ambiente , Hipertensión/tratamiento farmacológico , Hipoglucemiantes/provisión & distribución , Lípidos/provisión & distribuciónRESUMEN
OBJECTIVE: To evaluate the induction of DNA damage in peripheral blood mononuclear cells of patients with sickle cell disease, SS and SC genotypes, treated with hydroxyurea. METHODS: The study subjects were divided into two groups: one group of 22 patients with sickle cell disease, SS and SC genotypes, treated with hydroxyurea, and a Control Group composed of 24 patients with sickle cell disease who were not treated with hydroxyurea. Peripheral blood samples were submitted to peripheral blood mononuclear cell isolation to assess genotoxicity by the cytokinesis-block micronucleus cytome assay, in which DNA damage biomarkers - micronuclei, nucleoplasmic bridges and nuclear buds - were counted. RESULTS: Patients with sickle cell disease treated with hydroxyurea had a mean age of 25.4 years, whereas patients with sickle cell disease not treated with hydroxyurea had a mean age of 17.6 years. The mean dose of hydroxyurea used by the patients was 12.8mg/kg/day, for a mean period of 44 months. The mean micronucleus frequency per 1,000 cells of 8.591±1.568 was observed in the Hydroxyurea Group and 10.040±1.003 in the Control Group. The mean frequency of nucleoplasmic bridges per 1,000 cells and nuclear buds per 1,000 cells for the hydroxyurea and Control Groups were 0.4545±0.1707 versus 0.5833±0.2078, and 0.8182±0.2430 versus 0.9583±0.1853, respectively. There was no statistically significant difference between groups. CONCLUSION: In the study population, patients with sickle cell disease treated with the standard dose of hydroxyurea treatment did not show evidence of DNA damage induction.
Asunto(s)
Anemia de Células Falciformes/genética , Daño del ADN/efectos de los fármacos , Hidroxiurea/farmacología , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Adolescente , Adulto , Anemia de Células Falciformes/tratamiento farmacológico , Niño , Preescolar , Citocinesis , Daño del ADN/genética , Femenino , Humanos , Hidroxiurea/efectos adversos , Hidroxiurea/uso terapéutico , Masculino , Pruebas de Micronúcleos , Persona de Mediana Edad , Pruebas de Mutagenicidad , Mutación/efectos de los fármacos , Inhibidores de la Síntesis del Ácido Nucleico/efectos adversos , Inhibidores de la Síntesis del Ácido Nucleico/uso terapéutico , Adulto JovenRESUMEN
The aim of this work was to synthesize and characterize the inclusion compounds formed by the complexation of ß-cyclodextrin (ßCD) with insecticides from the class of benzoylphenylureas (BPUs), named novaluron (NOV) and diflubenzuron (DIF), beyond evaluate their larvicidal activity against Aedes aegypti larvae. Solid state characterization by FTIR showed changes in the main peaks of BPUs and ßCD, suggesting the formation of inclusion compounds in solid phase. DTA and TGA thermal analysis showed changes in temperatures of BPUs decomposition as result of molecular interactions. 1H NMR experiments allowed to observe the occurrence of interactions in solution through changes in chemical shifts of BPUs aromatic hydrogens. However, the presence of H-H intermolecular correlations in 2D ROESY was found only for the DIF/ßCD complex, suggesting different topology for each complex. Such hypothesis was corroborated by thermodynamic analysis using ITC, which showed different profile of titration curves, beyond endothermic and exothermic interactions for NOV/ßCD and DIF/ßCD complexes, respectively. DLS titrations of BPUs or BPUs/ßCD DMSO solutions in aqueous solution demonstrated that the spontaneously formed hydrophobic nanoprecipitates (HNPs) have different profile of sizes depending on the BPU/ßCD system, corroborating also with the hypothesis about the existence of different topologies for each complex. Finally, the HNPs of inclusion compounds showed to be more efficient than free BPUs, allowing proposing a new insecticide formulation.
RESUMEN
ABSTRACT Objective To evaluate the induction of DNA damage in peripheral blood mononuclear cells of patients with sickle cell disease, SS and SC genotypes, treated with hydroxyurea. Methods The study subjects were divided into two groups: one group of 22 patients with sickle cell disease, SS and SC genotypes, treated with hydroxyurea, and a Control Group composed of 24 patients with sickle cell disease who were not treated with hydroxyurea. Peripheral blood samples were submitted to peripheral blood mononuclear cell isolation to assess genotoxicity by the cytokinesis-block micronucleus cytome assay, in which DNA damage biomarkers - micronuclei, nucleoplasmic bridges and nuclear buds - were counted. Results Patients with sickle cell disease treated with hydroxyurea had a mean age of 25.4 years, whereas patients with sickle cell disease not treated with hydroxyurea had a mean age of 17.6 years. The mean dose of hydroxyurea used by the patients was 12.8mg/kg/day, for a mean period of 44 months. The mean micronucleus frequency per 1,000 cells of 8.591±1.568 was observed in the Hydroxyurea Group and 10.040±1.003 in the Control Group. The mean frequency of nucleoplasmic bridges per 1,000 cells and nuclear buds per 1,000 cells for the hydroxyurea and Control Groups were 0.4545±0.1707 versus 0.5833±0.2078, and 0.8182±0.2430 versus 0.9583±0.1853, respectively. There was no statistically significant difference between groups. Conclusion In the study population, patients with sickle cell disease treated with the standard dose of hydroxyurea treatment did not show evidence of DNA damage induction.
RESUMO Objetivo Avaliar o efeito da indução de danos ao DNA em células monocelulares do sangue periférico de pacientes com doença falciforme, genótipos SS e SC, tratados com hidroxiureia. Métodos Os sujeitos da pesquisa foram divididos em dois grupos: um de 22 pacientes com doença falciforme genótipos SS e SC tratados com hidroxiureia, e o outro controle, composto por 24 pacientes com doença falciforme que não eram tratados com o fármaco. As amostras de sangue periférico foram submetidas ao isolamento de células mononucleares do sangue periférico para avaliação da genotoxicidade pelo ensaio de micronúcleo citoma com bloqueio da citocinese, tendo sido quantificados os biomarcadores de danos ao DNA - micronúcleos, pontes nucleoplasmáticas e brotamento nuclear. Resultados Os pacientes com doença falciforme tratados com hidroxiureia apresentaram média de idade de 25,4 anos, enquanto aqueles com doença falciforme não tratados com hidroxiureia tiveram média de idade de 17,6 anos. A dose média de hidroxiureia utilizada pelos pacientes foi de 12,8mg/kg/dia, por período médio de 44 meses. A frequência média de micronúcleos por 1.000 células de 8,591±1,568 foi observada no Grupo Hidroxiureia e de 10,040±1,003 no Grupo Controle. Adicionalmente, a frequência média de pontes nucleoplasmáticas por 1.000 células e brotamento nuclear por 1.000 células para o Grupo Hidroxiureia e Controle foi de 0,4545±0,1707 versus 0,5833±0,2078, e de 0,8182±0,2430 versus 0,9583±0,1853, respectivamente. Não houve diferença estatisticamente significativa entre os grupos. Conclusão Na população estudada de pacientes com doença falciforme com tratamento em dose padrão de hidroxiureia, não houve evidência de indução de danos ao DNA.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Adulto Joven , Daño del ADN/efectos de los fármacos , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Hidroxiurea/farmacología , Anemia de Células Falciformes/genética , Daño del ADN/genética , Pruebas de Micronúcleos , Inhibidores de la Síntesis del Ácido Nucleico/efectos adversos , Inhibidores de la Síntesis del Ácido Nucleico/uso terapéutico , Citocinesis , Hidroxiurea/efectos adversos , Hidroxiurea/uso terapéutico , Anemia de Células Falciformes/tratamiento farmacológico , Persona de Mediana Edad , Pruebas de Mutagenicidad , Mutación/efectos de los fármacosRESUMEN
Curcumin (CMN) is the principal active component derived from the rhizome of Curcuma longa (Curcuma longa L.). It is a liposoluble polyphenolic compound that possesses great therapeutic potential. Its clinical application is, however, limited by the low concentrations detected following oral administration. One key strategy for improving the solubility and bioavailability of poorly water-soluble drugs is solid dispersion, though it is not known whether this technique might influence the pharmacological effects of CMN. Thus, in this study, we aimed to evaluate the antioxidant and antigenotoxic effects of CMN formulated in a solid dispersion (CMN SD) compared to unmodified CMN delivered to Wistar rats. Cisplatin (cDDP) was used as the damage-inducing agent in these evaluations. The comet assay results showed that CMN SD was not able to reduce the formation of cDDP-DNA crosslinks, but it decreased the formation of micronuclei induced by cDDP and attenuated cDDP-induced oxidative stress. Furthermore, at a dose of 50 mg/kg b.w. both CMN SD and unmodified CMN increased the expression of Tp53 mRNA. Our results showed that CMN SD did not alter the antigenotoxic effects observed for unmodified CMN and showed effects similar to those of unmodified CMN for all of the parameters evaluated. In conclusion, CMN SD maintained the protective effects of unmodified CMN with the advantage of being chemically water soluble, with maximization of absorption in the gastrointestinal tract. Thus, the optimization of the physical and chemical properties of CMN SD may increase the potential for the therapeutic use of curcumin.
RESUMEN
The purpose of this study was to investigate the neuroprotective effect of a water-soluble formulation of coenzyme Q10 (WS-CoQ10) in PC12 cells exposed to cisplatin, a chemotherapeutic agent with a dose-limiting factor due to neurotoxicity. In the cytokinesis-block micronucleus cytome assay (CBMN Cyt), WS-CoQ10 (at concentrations of 0.1, 0.5 and 1.0µgmL(-1)) protected PC12 cells from cisplatin-induced DNA damage (0.1µgmL(-1)), reducing the frequency of micronuclei (MNi) and nuclear buds (NBUDs). WS-CoQ10 did not alter the mRNA expression levels of Tp53 (at a concentration of 1.0µgmL(-1)) and exhibited neuroprotective activity by stimulating cisplatin-inhibited neurite outgrowth in nerve growth factor (NGF)-differentiated PC12 cells (at a concentration of 0.1µgmL(-1)). In conclusion, WS-CoQ10 protected the PC12 cells from cisplatin-induced DNA damage and neurotoxicity. Moreover, the neuroprotective effects of WS-CoQ10 suggest a possible application in chemotherapeutic protocols.
Asunto(s)
Antineoplásicos/toxicidad , Cisplatino/toxicidad , Daño del ADN/efectos de los fármacos , Ubiquinona/análogos & derivados , Análisis de Varianza , Animales , Diferenciación Celular/efectos de los fármacos , Ensayo Cometa , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Factor de Crecimiento Nervioso/farmacología , Células PC12 , ARN Mensajero/metabolismo , Ratas , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ubiquinona/farmacologíaRESUMEN
The potential neuroprotective benefits of curcumin against cisplatin neurotoxicity were investigated. Curcumin is a polyphenol derived from the rhizome of Curcuma longa whose pharmacological effects include antioxidant, anti-inflammatory and anti-cancer properties. Cisplatin is a potent chemotherapeutic drug with activity against a wide variety of tumors, although it has notorious side effects. Cisplatin neurotoxicity is clinically evident in patients that have undergone a full course of chemotherapy and develop a peripheral neuropathy that may affect the treatment regimen and the patient's qualify of life. In this study, we examined whether curcumin can protect against cisplatin neurite outgrowth inhibition in PC12 cells, which is an indicator of the protective potential against neuropathy. We also investigated whether curcumin affects cisplatin effectiveness by analyzing the modulation of p53 gene expression and its effect on cisplatin cytotoxicity in HepG2 tumor cells. Non-cytotoxic concentrations of curcumin reduced in vitro neurotoxicity of cisplatin in PC12 cells. The treatment of PC12 cells with cisplatin (10µg/mL) significantly reduced neurite outgrowth. The tested concentration of curcumin (1.0 and 10µg/mL) did not result in neurite toxicity but nevertheless diminished cisplatin-induced inhibition of neurite outgrowth by up to 50% (p<0.05). Our results indicate that curcumin does not compromise cisplatin's anticancer activity. Curcumin neither suppressed p53 mRNA transcription nor protected tumor cells against cisplatin cytotoxicity. These results indicate that curcumin may reduce cisplatin-induced neurotoxicity, and clinical studies should potentially be considered.
Asunto(s)
Antineoplásicos/toxicidad , Diferenciación Celular , Cisplatino/toxicidad , Curcumina/farmacología , Factor de Crecimiento Nervioso/metabolismo , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Supervivencia Celular/efectos de los fármacos , Citoprotección , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neuritas/efectos de los fármacos , Neuritas/metabolismo , Neuritas/patología , Neuronas/metabolismo , Neuronas/patología , Células PC12 , ARN Mensajero/metabolismo , Ratas , Transcripción Genética/efectos de los fármacos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Bixin is the main carotenoid found in annatto seeds (Bixa orellana L.) and is responsible for their reddish-orange color. The antioxidant properties of this compound are associated with its ability to scavenge free radicals, which may reduce damage and protect tissues against toxicity caused by anticancer drugs such as cisplatin. In this study, the genotoxicity and antigenotoxicity of bixin on cisplatin-induced toxicity in PC12 cells was assessed. Cytotoxicity was evaluated using the MTT assay, mutagenicity, genotoxicity, and protective effect of bixin were evaluated using the micronucleus test and comet assay. PC12 cells were treated with bixin (0.05, 0.08, and 0.10µg/mL), cisplatin (0.1µg/mL) or a combination of both bixin and cisplatin. Bixin was neither cytotoxic nor genotoxic compared to the controls. In the combined treatment bixin significantly reduced the percentage of DNA in tail and the frequency of micronuclei induced by cisplatin. This result suggests that bixin can function as a protective agent, reducing cisplatin-induced DNA damage in PC12 cells, and it is possible that this protection could also extend to neuronal cells. Further studies are being conducted to better understand the mechanisms involved in the activity of this protective agent prior to using it therapeutically.
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Antineoplásicos/toxicidad , Antioxidantes/farmacología , Carotenoides/farmacología , Cisplatino/toxicidad , Animales , Ensayo Cometa , Relación Dosis-Respuesta a Droga , Pruebas de Micronúcleos , Células PC12 , RatasRESUMEN
A very appropriate method for antigenotoxicity evaluation of antioxidants is the comet assay, since this analytical method detects initial DNA lesions that are still subject to repair; in other words, lesions that are very associated to damages resulting from the generation and subsequent action of reactive species. However, a solid evaluation should be developed in order to avoid inexact interpretations. In our study, besides the association of curcumin with cisplatin, curcumin and cisplatin agents were also tested separately. Classical genotoxic compounds, when tested by the comet assay, present an increase in the nucleoid tail; however, the cisplatin treatment has resulted in a decrease of DNA migration. This was an expected effect, as the cross-links between cisplatin and DNA decrease the DNA electrophoretic mobility. A similar effect was observed with the curcumin treatment, which decreased the nucleoid tail. Such effect was not expected and reinforced the necessity of including in the study, separate treatment groups with potentially antigenotoxic substances. The comet assay results have been analyzed using specific software for image analysis, as well as the classical visual analysis, and we have observed that the effect of decrease in DNA electrophoretic mobility was more easily observed when the data were analyzed by the software.
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Antineoplásicos/toxicidad , Cisplatino/toxicidad , Ensayo Cometa , Curcumina/toxicidad , Daño del ADN , Animales , Relación Dosis-Respuesta a Droga , Procesamiento de Imagen Asistido por Computador , Mutágenos/toxicidad , Células PC12 , RatasRESUMEN
Neurotoxicity induced by reactive oxygen species can appear as an adverse effect of chemotherapy treatment with platinum compounds, such as cisplatin. The use of this drug in clinical practice is limited due to its adverse effects, including nephrotoxicity, ototoxicity, neurotoxicity and genotoxicity. Functional foods or nutraceuticals have demonstrated potential neuroprotective activity in several experiments and models. This study aimed to investigate the possible cytotoxicity and genotoxicity/antigenotoxic effects of curcumin in PC12 cells exposed to cisplatin. Cell viability and genotoxicity/antigenotoxicity were evaluated by the MTT assay and micronucleus test, respectively. PC12 cells were treated with different concentrations of cisplatin and curcumin (0.5 -- 128 microg/mL). Analysis of the results showed that high concentrations of curcumin were cytotoxic and increased micronuclei frequency compared to the control group. In the associated treatments, at all three concentrations evaluated, curcumin significantly reduced the total frequency of micronuclei induced by cisplatin. Determining the cytotoxic and genotoxic/antigenotoxic effects of this frequently used antioxidant in a neuronal model is important to assess possible hazards when combined with other chemical agents, including chemotherapy drugs used in cancer therapy.