Intoxicação aguda com clorpirifós tem impacto distinto na sobrevida e função cardiorrespiratória de ratos hipertensos e normotensos

• Ano de defesa: 2023
• Autor(a) principal: Aitken, Andrew Vieira
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso embargado
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Mestrado em Ciências Farmacêuticas; Centro de Ciências da Saúde; UFES; Programa de Pós-Graduação em Ciências Farmacêuticas
• Palavras-chave em Português: Clorpirifós; Ratos espontaneamente hipertensos; Toxicidade; Estresse oxidativo; Inflamação; SHR; Cardiovascular; Compostos organofosforados; Hipertensão; subject.br-rjbn; Farmácia
• Link de acesso: http://repositorio.ufes.br/handle/10/16757

Hypertension is the most important and well-known risk factor for development of cardiovascular disease (CVD). Additionally, other factors such as acute organophosphate (OP) poisoning have been pointed as a CVD risk factor. However, no studies have compared the cardiorespiratory effects induced by intoxication with OP in hypertensive and normotensive situations. Therefore, our study aimed to evaluate and compare acute toxicity and cardiorespiratory effects induced by the OP, chlorpyrifos (CPF), in normotensive and hypertensive rats. In order to study this, adult, male, Wistar and Spontaneously Hypertensive rats (SHR) were injected, intraperitoneally (i.p.) with saline or with CPF at the doses of 10, 20 and 30 mg/kg and evaluated for acute toxicity and lethality and 48 hours after testing, brainstem samples were collected for assays of oxidative stress and inflammation. Independent groups of animals were submitted to catheterization of femoral vein and artery under anesthesia with ketamine/xylazine (70/10 mg.kg-1 , i.p.) and 24 hours after rats were injected with saline or CPF (20mg/kg). 24 hours after the injections, baseline cardiorespiratory parameters were recorded and the Bezold-Jarisch Reflex (BJR), chemoreflex and cardiac autonomic tone were evaluated. After this, brainstem and blood samples were obtained for quantification of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity. For data analysis we used generalized estimating equations (GEE), three-way ANOVA for repeated measures and two-way ANOVA, followed by Bonferroni and Tukey post-hoc, when necessary. Hypertensive rats presented more intense acute toxicity signs following CPF intoxication and 8,34% lethality in non operated animals and 33% in animals previously submitted to catheterization. Intoxication with CPF attenuated baseline ventilation in SHR, impaired the hypotensive and bradycardic responses of BJR in Wistar and attenuated tachypneic response of chemoreflex in both strains. CPF promoted inhibition of AChE and BuChE enzyme activities, increased levels of advanced oxidative protein products, nitrite, nitrate, as well as elevated expression of tumor necrosis factor (TNF) and angiotensin-1 converting enzyme in Wistar rats, without evoking changes in SHR. Our findings show that SHR presented increased susceptibility to acute toxicity and lethality to CPF, in doses that were sublethal to normotensive animals. We also show that cardiorespiratory reflexes were differentially impacted by intoxication with CPF in hypertensive and normotensive rats and that cardiorespiratory disfunction seems to be associated with interference of cholinergic transmission, oxidative stress, and inflammation. These findings suggest an increased susceptibility to acute toxicity in hypertension, which could indicate a significant risk to vulnerable populations