Role of Oxidative Stress and Mitochondrial Dysfunction in Sepsis and Potential Therapies

Konstantinos Mantzarlis, Vasiliki Tsolaki, Epaminondas Zakynthinos, Konstantinos Mantzarlis, Vasiliki Tsolaki, Epaminondas Zakynthinos

Abstract

Sepsis is one of the most important causes of death in intensive care units. Despite the fact that sepsis pathogenesis remains obscure, there is increasing evidence that oxidants and antioxidants play a key role. The imbalance of the abovementioned substances in favor of oxidants is called oxidative stress, and it contributes to sepsis process. The most important consequences are vascular permeability impairment, decreased cardiac performance, and mitochondrial malfunction leading to impaired respiration. Nitric oxide is perhaps the most important and well-studied oxidant. Selenium, vitamin C, and 3N-acetylcysteine among others are potential therapies for the restoration of redox balance in sepsis. Results from recent studies are promising, but there is a need for more human studies in a clinical setting for safety and efficiency evaluation.

Figures

Figure 1
Figure 1
The mechanism of cytopathic hypoxia. The production of NO inhibits normal function of the respiratory complex IV interrupting the normal transport of electrons. O₂− production is enhanced and reacts with NO inhibiting complex I normal function. NO, nitric oxide; NOS, nitric oxide synthase; ADP, adenosine diphosphate; ATP, adenosine triphosphate.
Figure 2
Figure 2
Mechanism of apoptosis. Mitochondrial damage by ROS releases cytochrome C, which contributes to the formation of apoptosome. The reaction of apoptosome with caspaces initiates cell apoptosis via DNA fragmentation and chromatin condensation. ROS, reactive oxygen species; Cyt C, cytochrome C; DNA, deoxyribonucleic acid.

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