Effect of a mitochondria-targeted vitamin E derivative on mitochondrial alteration and systemic oxidative stress in mice

Abstract

The objective of the present study was to determine whether a mitochondria-targeted vitamin E derivative (MitoVit E) would affect certain mitochondrial parameters, as well as systemic oxidative stress. A total of sixty-four mice were fed a high-fat (HF) diet for 5 weeks. They were then switched to either a low-fat (LF) or a medium-fat (MF) diet, and administered orally with MitoVit E (40 mg MitoVit E/kg body weight) or drug vehicle (10 % (v/v) ethanol in 0·9 % (w/v) NaCl solution), every other day for 5 weeks. Mitochondrial ATP and H 2 O 2 production rates in both the liver and the gastrocnemius were not affected by MitoVit E administration in either LF or MF diet-fed mice. However, the number and average size of the subsarcolemmal mitochondria, but not the intermyofibrillar mitochondria, from the soleus muscle were significantly higher in the MF group receiving MitoVit E (MF-E) than in the MF group receiving vehicle only (MF-C). After the mice were switched from the HF diet to the four dietary treatments (LF-C, LF-E, MF-C and MF-E), the decrease in urinary isoprostane concentration was significantly greater in the LF-E group than in the other three groups during the whole study (weeks 6-10). In addition, MitoVit E significantly increased plasma superoxide dismutase (SOD) activity in the MF diet-fed group without affecting plasma glutathione peroxidase activity or H 2 O 2 levels. Overall, these data suggest that MitoVit E affects subsarcolemmal mitochondrial density and systemic oxidative stress parameters such as plasma SOD activity and urinary isoprostane concentration.

Physiological changes due to hepatotoxicity and the protective role of some medicinal plants

“…Hence, the role of oxidant agents in cells is complex and depends on the balance between oxidant and antioxidant particles. Protective actions against ROS are performed by several enzymes [(e.g., superoxide dismutase (SOD), catalase and glutathione peroxidase)] as well as nonenzymatic compounds (e.g., tocopherol, vitamin E, beta-carotene, ascorbate and glutathione (GSH)) (Mao et al, 2011). When the capacity of this antioxidant system decreases, the level of inactivated ROS rises.…”

α-Tocopherol incorporation in mitochondria and microsomes upon supranutritional vitamin E supplementation

“…Recently, Murphy and co-workers developed a series of mitochondria-targeted antioxidants by conjugation with triphenylphosphonium cations, which can permeate lipid bilayers easily and accumulate manyfold within the mitochondria. One of these mitochondria-targeted antioxidants is a mitochondria-targeted vitamin E derivative (Mao et al 2011). The molecule rapidly permeates lipid bilayers and because of the large mitochondrial membrane potential (negative inside) accumulates several hundredfold inside isolated mitochondria and within mitochondria in cultured cells (Smith et al 2003).…”

“…The lipids associated with the subcellular organelles (e.g., mitochondria and microsomes) are especially susceptible to oxidation by virtue of their high contents of phospholipids containing relatively large amounts of polyunsaturated fatty acids (Pearson et al 1977). Oxidative stress, characterized by increased generation of reactive oxygen species (ROS), and subsequent damage to mitochondria, has been proposed to cause a wide range of metabolic disorders (Mao et al 2011). It has been estimated that as much as 1-2% of all oxygen consumed may result in the formation of ROS, with the vast majority of ROS being generated in the mitochondria (Gille and Sigler 1995;Ischiropoulos and Beckman 2003).…”

“…Interest in preventing oxidant-induced pathologies and reduced stabilization of polyunsaturated fatty acids in the mitochondria and other subcellular fractions has therefore led to studies on antioxidant therapy. Recently, it was claimed (Mao et al 2011) that the effectiveness of antioxidant therapy seems to be largely limited by the poor capacity to accumulate specifically within the mitochondria. However, there are actually limited amount of data available on the incorporation of vitamin E and other antioxidants into supranutritional dietary levels.…”

Reversal of doxorubicin resistance in breast cancer by mitochondria-targeted pH-responsive micelles

“…Mitochondrion, a critical subcellular organelle, is usually referred to the cellular power source since it controls ATP synthesis [13]. The evidence accumulated to date indicates that mitochondria-associated apoptosis and energy metabolism could play important roles in cancer chemotherapy since the mitochondrion is also a crucial regulator of cell death [14][15][16][17].…”