Mitochondrial electron transport chain disruption and oxidative stress in lipopolysaccharide-induced cardiac dysfunction in rats and mice.

Abstract

Sepsis, characterized by severe systemic inflammation and an excessive immune response to infection, is frequently triggered by bacterial endotoxins like lipopolysaccharide (LPS) from Gram-negative bacteria. Moreover, sepsis-induced cardiac dysfunction remains a leading cause of mortality. This study aims to elucidate the effects of LPS-induced cardiac injury on mitochondrial damage, oxidative stress, and subsequent cardiac dysfunction. LPS injections (in rats and mice) for three days (1.5 mg/kg) impacted the body weight and increased cardiac TNF-α. Additionally, it decreased mitochondrial complexes I and II activities while complexes III and IV remained unaffected. Disturbed in mitochondrial electron transport chain leads to an increase in reactive oxygen species (ROS). Indeed, LPS treatment significantly increased mitochondrial hydrogen peroxide production, reduced the activity of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase activity. This was accompanied by decreased mitochondrial and cytosolic sulfhydryl proteins and parallel increased cellular lipid peroxidation in the presence or absence of Fe²⁺. LPS-treated samples had increased glutathione s-transferase activity, which may be an attempt of the cell to remove toxic lipid peroxidation products. In a more acute Langendorff-perfused rat hearts, LPS infusion (0.5 μg/mL) induced a significant elevation in left ventricular end-diastolic pressure and a decrease in left ventricular developed pressure. These findings elucidate the harmful mitochondrial and oxidative effects of LPS in cardiac tissue and could help the development of targeted therapies to mitigate the adverse effects of sepsis-induced cardiac dysfunction.