EXPLORING LIPOPOLYSACCHARIDE-INDUCED CARDIAC DYSFUNCTION: INSIGHTS INTO THE EFFECTS OF MITOCHONDRIAL AND OXIDATIVE STRESS
Sepsis. Mitochondria. Oxidative stress.
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