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Type 2 diabetes can increase the risk of skeletal muscle dysfunction and, consequently, that of cardiovascular diseases, including coronary artery disease and stroke. It is also related to a reduced capacity for exercise, but the underlying mechanism is only partially understood. There are several factors that contribute to the development of skeletal muscle dysfunction, of which oxidative stress and mitochondrial dysfunction are among the most important. This review discusses the role of oxidative stress in the development and progression of skeletal and cardiac dysfunction associated with diabetes. It also provides an overview of the potential actions of antioxidants in general and mitochondria-targeted antioxidants in particular in the treatment of muscle dysfunction in type 2 diabetes.

Mitochondria play an important role in controlling the bioenergetic status of cells in physiological conditions. Consequently, mitochondrial dysfunction leads to a range of human vascular diseases in humans. Although the molecular mechanisms responsible for mitochondria-mediated disease processes are not altogether clear, oxidative stress appears to be closely linked to the subsequent increase in the amount of free radicals. Accordingly, strategies for the targeted deliv- ery of antioxidants to mitochondria are being developed. In this review, we shall briefly discuss the metabolism of cellular reactive oxygen species and its role in pathophysiology, currently available antioxidants and possible reasons for their in- effectiveness in ameliorating oxidative stress-mediated diseases, and recent developments in mitochondria-targeted anti- oxidants (in particular mitochondria-targeted vitamin E) and their potential for the treatment of cardiovascular disease.

Severe sepsis leading to shock is the principal cause of death in intensive care units. It is a systemic inflammatory response caused by excessive secretion of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNFalpha) and reactive oxygen species (ROS), mainly induced by endotoxin (a major component of the Gram-negative bacterial outer membrane). Immune cells use ROS in order to support their functions and need adequate levels of antioxidant defenses to avoid harmful effects of an excessive ROS production. In addition, nitric oxide (NO) is thought to play a key role in the pathogenesis of sepsis and in the development of multiple organ failure. This article discusses the toxic effects of endotoxin, paying particular attention to cardiovascular damage. It continues by analysing the mechanism by which endotoxin is recognized by specific cells of the immune system, and the pathway leading to nuclear factor-kappaB (NF-kappaB) activation and pro-inflammatory gene transcription. In relation to this process, this review focuses on the involvement of reactive oxygen and nitrogen species. Finally, the protective role of antioxidants against homeostatic disturbances such as those caused by endotoxin toxicity, their potential clinical use and the effects on the redox state of the immune cells is discussed.