Ivermectina na lesão renal aguda por isquemia-reperfusão: estudo experimental
Data
2023-10-11
Autores
Budini, Raphael Cuencas [UNIFESP]
Orientadores
Fonseca, Cassiane Dezoti da [UNIFESP]
Tipo
Trabalho de conclusão de curso de graduação
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: Lesão Renal Aguda (LRA) é uma síndrome caracterizada pela diminuição da capacidade de excreção renal vista pelo aumento dos níveis séricos de creatinina e/ou diminuição do débito urinário. A infecção pelo SARS-CoV-2 vislumbrou o uso de medicamentos com possíveis potenciais terapêuticos. Dentre eles destacou-se a ivermectina, a qual proporcionou efeitos adversos associados à dose ingerida, como cefaleia, febre e visão turva. Além disso, pouco se sabe sobre o uso da Ivermectina a longo prazo. Objetivo: Avaliar o efeito da ivermectina em animais submetidos ao fator de risco isquemia-reperfusão. Metodologia: Foram utilizados 30 animais, machos, de raça Wistar, com peso variando entre 250 e 290g, randomizados de acordo com os seguintes grupos : a) SHAM (n = 10): animais que foram utilizados para a simulação do ato cirúrgico, sem clampeamento dos pedículos renais; b) Isquemia (n = 5): animais que foram utilizados para o clampeamento dos pedículos renais por um período de 30 minutos; c) SHAM + Ivermectina (n = 5): animais SHAM que receberam 10mg/kg de Ivermectina, via oral, uma vez ao dia, durante um período de cinco dias; d) Isquemia + Ivermectina (n = 5): animais Isquemia que receberam 10mg/kg de Ivermectina, via oral, uma vez ao dia, durante um período de cinco dias. Parâmetros fisiológicos como peso, ingestão hídrica e de alimento, razão entre o peso do rim e o do animal, função renal (clearance de creatinina) e perfil oxidativo (peróxidos e TBARS urinários) foram avaliados e seus resultados foram expressos em média ± desvio padrão. A variância entre os grupos foi analisada por meio do teste One Way ANOVA, seguida do pós-teste de comparações múltiplas de Tukey do programa estatístico Graph-Pad Prism version-3 for Windows®. Foram considerados significativos, valores de p < 0,05. Comitê de ética: Aprovado pela Comissão de Ética no Uso de Animais (CEUA) sob o protocolo nº 8126260822. Resultados: Foi observado aumento da relação peso/rim nos animais medicados com Ivermectina, especialmente no grupo Isquemia + Ivermectina. O valor de creatinina sérica aumentou nos grupos de animais medicados com a Ivermectina. A ivermectina causou diminuição do clearance de creatinina sobretudo nos grupos associados à isquemia renal. O estresse oxidativo foi maior no grupo ivermectina com isquemia. Conclusão: A ivermectina demostrou atividade nefrotóxica baseada no mecanismo de nefrose osmótica, e evidenciou também uma piora adicional dos parâmetros de função renal e estresse oxidativo quando associada a lesão renal prévia.
Introduction: Acute Kidney Injury (AKI) is a syndrome characterized by decreased renal excretion capacity seen by increased serum creatinine levels and/or decreased urinary output. The SARSCoV2 infection envisioned the use of drugs with possible therapeutic potential. Among them, ivermectin stands out, which provided adverse effects associated with the ingested dose, such as headache, fever and blurred vision. In addition, little is known about the longterm use of Ivermectin. Objective: To evaluate the effect of ivermectin in animals submitted to ischemiareperfusion risk factor. Methodology: We used 30 male Wistar animals, weighing between 250 and 290g, randomized according to the following groups: a) SHAM (n = 10): animals that were used to simulate the surgical procedure, without clamping the renal pedicles; b) Ischemia (n = 5): animals that were used to clamp the renal pedicles for a period of 30 minutes; c) SHAM + Ivermectin (n = 5): SHAM animals that received 10mg/kg of Ivermectin, orally, once a day, for a period of five days; d) Ischemia + Ivermectin (n = 5): Ischemia animals that received 10mg/kg of Ivermectin, orally, once a day, for a period of five days. Physiological parameters such as weight, water and food intake, ratio between kidney and animal weight, renal function (creatinine clearance) and oxidative profile (urinary peroxides and TBARS) were evaluated and their results were expressed as mean ± standard deviation . Variance between groups was analyzed using the One Way ANOVA test, followed by Tukey's multiple comparisons posttest using the statistical program GraphPad Prism version3 for Windows®. Values of "p < 0.05" were considered significant. Ethics Committee: Approved by the Animal Use Ethics Committee (CEUA) under protocol nº 8126260822. Results: An increase in the weight/kidney ratio was observed in animals medicated with Ivermectin, especially in the Ischemia + Ivermectin group. The serum creatinine value increased in groups of animals medicated with Ivermectin. Ivermectin caused a decrease in creatinine clearance, especially in groups associated with renal ischemia. Oxidative stress was greater in the ivermectin group with ischemia. Conclusion: Ivermectin demonstrated nephrotoxic activity based on the mechanism of osmotic nephrosis, and also showed an additional worsening of renal function parameters and oxidative stress when associated with previous renal injury.
Introduction: Acute Kidney Injury (AKI) is a syndrome characterized by decreased renal excretion capacity seen by increased serum creatinine levels and/or decreased urinary output. The SARSCoV2 infection envisioned the use of drugs with possible therapeutic potential. Among them, ivermectin stands out, which provided adverse effects associated with the ingested dose, such as headache, fever and blurred vision. In addition, little is known about the longterm use of Ivermectin. Objective: To evaluate the effect of ivermectin in animals submitted to ischemiareperfusion risk factor. Methodology: We used 30 male Wistar animals, weighing between 250 and 290g, randomized according to the following groups: a) SHAM (n = 10): animals that were used to simulate the surgical procedure, without clamping the renal pedicles; b) Ischemia (n = 5): animals that were used to clamp the renal pedicles for a period of 30 minutes; c) SHAM + Ivermectin (n = 5): SHAM animals that received 10mg/kg of Ivermectin, orally, once a day, for a period of five days; d) Ischemia + Ivermectin (n = 5): Ischemia animals that received 10mg/kg of Ivermectin, orally, once a day, for a period of five days. Physiological parameters such as weight, water and food intake, ratio between kidney and animal weight, renal function (creatinine clearance) and oxidative profile (urinary peroxides and TBARS) were evaluated and their results were expressed as mean ± standard deviation . Variance between groups was analyzed using the One Way ANOVA test, followed by Tukey's multiple comparisons posttest using the statistical program GraphPad Prism version3 for Windows®. Values of "p < 0.05" were considered significant. Ethics Committee: Approved by the Animal Use Ethics Committee (CEUA) under protocol nº 8126260822. Results: An increase in the weight/kidney ratio was observed in animals medicated with Ivermectin, especially in the Ischemia + Ivermectin group. The serum creatinine value increased in groups of animals medicated with Ivermectin. Ivermectin caused a decrease in creatinine clearance, especially in groups associated with renal ischemia. Oxidative stress was greater in the ivermectin group with ischemia. Conclusion: Ivermectin demonstrated nephrotoxic activity based on the mechanism of osmotic nephrosis, and also showed an additional worsening of renal function parameters and oxidative stress when associated with previous renal injury.