Banca de QUALIFICAÇÃO: AGDA ALINE PEREIRA DE SOUSA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : AGDA ALINE PEREIRA DE SOUSA
DATE: 28/06/2024
TIME: 14:00
LOCAL: Sala de Videoconferência da Faculdade de Medicina - UFCA (campus Barbalha)
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, characterized by an uncontrolled immune response to a systemic
infection, is commonly triggered by bacterial endotoxins such as lipopolysaccharide (LPS) from

Gram-negative bacteria, playing a central role in severe inflammation. Additionally, sepsis-
induced cardiac dysfunction is one of the leading causes 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 from the Animal Use Committee. Cardiac function
analysis was performed using the Langendorff perfusion system. The activities of mitochondrial
complexes (I, II, III, and IV), antioxidant enzymes, and hydrogen peroxide levels were measured
spectrophotometrically. Statistical analysis was conducted using Student's t-test in GraphPad
Prism software. LPS treatment significantly reduced the activity of glutathione peroxidase,
glutathione reductase, and catalase. This was accompanied by a trend of decreased mitochondrial
sulfhydryl protein levels in cardiac samples from mice and in the cytosol of rats. 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 a cellular adaptive mechanism to try to
control oxidative stress. These results led us to examine the influence of LPS on the functionality
of mitochondrial complexes. These analyses revealed a significant decrease in complexes I and
II in the cardiac mitochondria of LPS-treated animals, while the activities of complexes III and
IV remained unchanged. In the hearts of rats perfused with Langendorff, LPS infusion (0.5 μg)
induced a significant elevation in left ventricular end-diastolic pressure and a decrease in left
ventricular developed pressure. 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 dysfunct

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