Teses em Farmacologia e Bioquímica (Doutorado) - FARMABIO/ICB
URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/13300
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Item Acesso aberto (Open Access) Avaliação anticonvulsivante e pró-convulsivante de óleos essenciais de Lippia origanoides e Rosmarinus officinalis em ratos: um estudoeletrofisiológico(Universidade Federal do Pará, 2025-05) ARAÚJO, Daniella Bastos de; HAMOY, Moisés; http://lattes.cnpq.br/4523340329253911; https://orcid.org/0000-0002-2931-4324Epilepsy is a neuronal disorder characterized by abnormal brain excitability, leading to seizures. Only about 66% of epileptic patients respond adequately to treatment with existing conventional anticonvulsants, making it necessary to investigate new antiepileptic drugs. The growing research on natural products and their pharmacological properties has become increasingly promising, particularly in the study of essential oils, already widely used in popular culture for the treatment of several diseases. The present studies evaluated the anti- and pro-convulsant effects of the essential oils of Lippia origanoides (LOEO) and Rosmarinus officinalis (EORO) in Wistar rats. We evaluated the essential oil of Lippia origanoides (LOEO) (100 mg/kg i. p.) in comparison with diazepam (DZP) (5 mg/kg i. p.) and the combined administration of these two substances to control seizures induced by pentylenetetrazole (PTZ) (60 mg/kg i. p.). This evaluation was carried out using 108 male Wistar rats, which were divided into two experiments. Experiment 1 – Behavioral evaluation and Experiment 2 – Electrocorticographic evaluation. With rosemary essential oil, we evaluated high doses in 54 Wistar rats, weighing between 180 and 200 g. The study consisted of three experiments: 1) behavioral monitoring of the animals after administration of 500 mg/kg i.p.; 2) electrocorticographic recordings after drug administration; 3) reaction to anticonvulsant drugs, where phenytoin, phenobarbital and diazepam (10 mg/kg i.p.) were administered. With LOEO, the animals presented a more intense decrease in respiratory rate when combined with LOEO + DZP. EEG recordings showed a reduction in firing amplitude in the groups treated with LOEO. Combined treatment with diazepam resulted in increased anticonvulsant effects, while with EORO, the results demonstrated an increase in the latency time for the onset of isolated clonic seizures without loss of the postural reflex. The animals showed a more intense decrease in respiratory rate when combined with LOEO + DZP. EEG recordings showed a reduction in firing amplitude in the groups treated with LOEO. Combined treatment with diazepam resulted in increased anticonvulsant effects. Treatment with LOEO was effective in controlling seizures, and its combination with diazepam may represent a future option for the treatment of difficult-to-control seizures, while treatment with EORO demonstrated an excitatory activity related to the reduction of GABAergic activity.Item Acesso aberto (Open Access) Contaminação por mercúrio e os impactos na saúde: o cenário da notificação no Brasil e análises teórica e prática na Amazônia(Universidade Federal do Pará, 2025-06) ARAÚJO, Amanda Lopes; ARRIFANO, Gabriela de Paula Fonseca; http://lattes.cnpq.br/3401378700297133; HTTPS://ORCID.ORG/0000-0003-2817-3539; LÓPEZ, Maria Elena Crespo; http://lattes.cnpq.br/9900144256348265; https://orcid.org/0000-0002-1335-6853The Amazon is a relevant case for studying the environmental and health impacts caused by mercury. Activities such as mining, deforestation, and large-scale development projects intensify the mobilization of this metal, posing challenges for public health surveillance—especially in areas where mercury exposure is chronic. Studies indicate that the accumulation of this metal in the body is associated with cardiovascular and neurological diseases, putting vulnerable populations at risk. This study analyzed the relationship between mercury contamination and public health in the Amazon. The specific objectives were: i) to explore notifications of human exposure/intoxication cases related to mercury; ii) to conduct a theoretical review of current knowledge on mercury contamination in the Amazon region; and iii) to carry out a cross-sectional epidemiological study in riverside communities of the Amazon, assessing cardiovascular risk through lipid and genetic profilesFor the study on epidemiological surveillance, data from the Notifiable Diseases Information System (SINAN) on exogenous intoxication were obtained online, covering the years 2007 to 2022. Two researchers independently analyzed and selected the cases using a standardized protocol. After extracting the relevant data from each record, analyses were conducted on the geographic distribution of cases, age, pregnancy status, and identification of specific codes. For the review, a comprehensive literature search was conducted, including scientific articles, reports, and relevant studies. This narrative review enabled both qualitative and quantitative analysis of the findings, focusing on key outcomes and implications for public health and the environment in the region. Finally, to assess the association between mercury and cardiovascular risk, anthropometric data were collected from participants. Lipid profiles and levels of apolipoproteins B (ApoB) and A-I (ApoA-I) were measured by spectrophotometry. Total mercury and methylmercury (MeHg) levels in hair samples were quantified using ICP- MS and GC-pyro-AFS. The polymorphisms rs662799, rs693, rs429358, and rs7412 (in apolipoprotein genes A-V, B, and E at positions 112 and 158, respectively) were genotyped by real-time PCR. SINAN recorded only 668 suspected/confirmed cases of mercury exposure over 16 years, with just 15.6% occurring in the Brazilian Amazon, highlighting severe underreporting in this region. The review showed that the mercury biogeochemical cycle in the Amazon is highly dynamic, influenced by mining, deforestation, and large-scale development projects, which contribute to widespread mercury mobilization and dissemination throughout the region. As a result, local populations showed exposure concentrations 2 to 6 times higher than reference doses. Additionally, the studied riverside population presented a dyslipidemia profile significantly correlated with mercury levels in hair. The ApoB/ApoA-I ratio was also positively correlated with mercury, supporting a possible causal relationship. Allelic distributions were similar to those described in other populations. Conclusions: Despite the availability of tools such as SINAN and the work of Community Health Agents, official data fail to reflect the actual exposure experienced by these populations. Underreporting of mercury exposure compromises the understanding of the true magnitude of the problem and hinders the implementation of effective public policies. This scenario particularly affects the Amazon region. The mercury cycle in the Amazon is unique and extremely complex, shaped by both natural features and human activities. Moreover, Amazonian populations exhibit higher exposure levels than other regions of the world. The analysis of a riverside population demonstrated for the first time: i) the association between mercury exposure and apolipoproteins related to cardiovascular risk in humans, ii) ApoB levels and the ApoB/ApoA-I ratio as the risk factors most strongly associated with mercury-related dyslipidemia in humans, and iii) the prevalence of high/moderate risk of acute myocardial infarction in this population, along with the genotypic profile of the three most frequent polymorphisms in apolipoproteins relevant to cardiovascular risk.