Oxidative stress and septic shock: metabolic aspects of oxygen-derived free radicals generated in the liver during endotoxemia

Abstract

This review describes the role of oxidative stress caused by endotoxin challenge in sepsis or septic shock symptoms. We observed that endotoxin injection resulted in lipid peroxide formation and membrane damage (near 60-150 kDa) in the livers of experimental animals, causing decreased levels of scavengers or quenchers of free radicals. The administration of a-tocopherol completely prevented injury to the liver plasma membrane caused by endotoxin, and suggested that lipid peroxidation by free radicals might occur in a tissue ischemic state, probably by disseminated intravascular coagulation (DIC), in endotoxemia. In mice, depression of Ca 21 -ATPase activity in the liver plasma membrane may contribute to the membrane damage caused by endotoxin, and the increase of [Ca 21 ] i in the liver cytoplasm may partially explain the oxidative stress that occurs in endotoxemia. It seems that endotoxin-induced free radical formation is regulated by Ca 21 mobilization. Moreover, we have suggested that the oxidative stress caused by endotoxin may be due, at least in part, to the changes in endogenous zinc or selenium regulation during endotoxemia. Interestingly, the extent of TNF-a-induced oxidative stress may be the result of a synergism between TNF-a and gut-derived endotoxin. It is likely that bacterial or endotoxin translocation plays a significant role in TNF-ainduced septic shock. On the other hand, although nitric oxide (NO) has been implicated in the pathogenesis of vascular hyporesponsiveness and hypotension in septic shock in our experimental model, it is unlikely that NO plays a significant role in liver injury caused by free radical generation in endotoxemia.

Heat-shock response protects peripheral blood mononuclear cells (PBMCs) from hydrogen peroxide-induced mitochondrial disturbance

“…*p<0.05 vs. each other as indicated cellular activation (Hansen et al 2006); however, a large amount of ROS formation when cells are receiving stress signals can lead to an imbalance of oxidants and antioxidants, causing oxidative stress. Related effects of oxidative stress have been noted and have been implicated in a variety of clinical conditions, including infectious diseases (Sakaguchi and Furusawa 2006), aging (Csiszar et al 2007), and autoimmune diseases (Nicolls et al 2007). Hydrogen peroxide is a small and diffusible molecule, and it can act as a second messenger of metabolic oxidative stress and induces oxidative damage to many cellular components indiscriminately (Clarkson and Thompson 2000;Ji 1999;Song et al 2005).…”

Common Pathogenic Mechanism in Development Progression of Liver Injury Caused by Non-Alcoholic or Alcoholic Steatohepatitis

“…TNF-α administered intravenously with nanogram quantities of the endotoxin has been reported to cause lethal shock, and it appears that TNF-α and endogenously produced endotoxin act synergistically in activating the complement system, which plays an important role in mediating tissue injury and lethality (Hsueh et al,1990;Leist et al, 1997;Sakaguchi and Furusawa, 2006). In addition, we have reported that the oxidative stress caused by TNF-α occurs as an enhancing effect of endotoxin or by bacterial translocation from the intestinal gut under reduction of RES function in various disease states, and that the effect of TNF-α may cause a marked increase of toxicity of oxidative stress by endotoxin (Sakaguchi and Furusawa, 2006;Sakaguchi et al,1996). In support of our findings, previous studies (Sakaguchi et al, 2000) have indicated that endogenously produced endotoxin may contribute to the extent of TNF-α-hypersensitivity caused by Dgalactosamine.…”

Immediate Effects of Chest Physiotherapy on Hemodynamic, Metabolic, and Oxidative Stress Parameters in Subjects With Septic Shock

“…Therefore, it is important to evaluate the potential of free radicals in sepsis and septic shock patients with metabolic disorders. 4 Indeed, the mitochondrion also plays an important role in cellular energy, and its structure and function are markedly affected by the physiopathology of sepsis. In particular, its high reactivity composes peroxynitrite, generated by the reaction of nitric oxide and superoxidase anions, mitochondrial inhibition enzymes and nucleic acids, and proteins and injured lipids.…”