Banca de DEFESA: AGDA ALINE PEREIRA DE SOUSA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : AGDA ALINE PEREIRA DE SOUSA
DATE: 01/08/2024
TIME: 14:00
LOCAL: Sala de Aula do Mestrado em Ciências da Saúde - Faculdade de Medicina - UFCA
TITLE:

EXPLORING LIPOPOLYSACCHARIDE-INDUCED CARDIAC DYSFUNCTION: INSIGHTS INTO THE EFFECTS OF MITOCHONDRIAL AND OXIDATIVE STRESS

KEY WORDS:

Sepsis. Mitochondria. Oxidative stress.

PAGES: 71
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

Sepsis is characterized by an uncontrolled immune response to systemic infection, commonly triggered by bacterial endotoxins such as lipopolysaccharide (LPS) from Gram-negative bacteria, playing a central role in severe inflammation. Moreover, sepsis-induced cardiac dysfunction is a leading cause of mortality. This study aims to determine the effects of LPS-induced cardiac injury on mitochondrial damage, oxidative stress, and subsequent cardiac dysfunction in mice and rats. Mice and rats were injected with LPS for three days (1.5 mg/kg), following approval by the Animal Use Committee. Cardiac function analysis was performed using the Langendorff perfusion system. Activities of mitochondrial complexes (I, II, III, and IV), antioxidant enzymes, and hydrogen peroxide levels were measured spectrophotometrically. Statistical analysis was performed using Student's t-test in GraphPad Prism software. LPS treatment significantly reduced the activities of glutathione peroxidase, glutathione reductase, and catalase. This was accompanied by a trend towards decreased levels of mitochondrial sulfhydryl proteins in mouse cardiac samples and in rat cytosol. Additionally, LPS treatment significantly increased mitochondrial hydrogen peroxide production and lipid peroxidation in treated animals, indicating increased oxidative stress. There was also a significant increase in glutathione S- transferase, as an adaptive mechanism by the cell to control oxidative stress. These results led us to examine the influence of LPS on mitochondrial complex functionality. These analyses revealed a significant decrease in complexes I and II in cardiac mitochondria of LPS-treated animals, while activities of complexes III and IV remained unchanged. In Langendorff-perfused rat hearts, LPS infusion (0.5 µg) induced a significant increase in left ventricular end-diastolic pressure and a decrease in total developed pressure by this same ventricle. In conclusion, this study sheds light on the detrimental effects of LPS-induced cardiac injury on mitochondrial integrity and function, leading to increased oxidative stress and subsequent cardiac dysfunction. These insights may pave the way for the development of targeted therapeutic interventions aimed at mitigating the deleterious consequences of sepsis-induced cardiac dysfunction.

COMMITTEE MEMBERS:
Presidente - HEBERTY DI TARSO FERNANDES FACUNDO
Externo ao Programa - 1242648 - JORGE ANDRE MATIAS MARTINS - nullInterna - MARIA ELIZABETH PEREIRA NOBRE
Interna - SALLY DE FRANCA LACERDA PINHEIRO