Antioxidative activity of thiophane [bis(3-(3,5-di-tret-butyl-4-hydroxyphenyl)propyl)sulfide]

The antioxidant activity, mutagenicity, and genotoxicity of bis(3-(3,5-di-tret-butyl-4-hydroxyphenyl)propyl)sulfide (thiophane) were studied using bacterial tests. The results of both an Ames test and SOS chromotest, as well as those studying the survival of E. coli cells deficient in enzymes responsible for the repair of DNA oxidative damage, testify to the fact that thiophane is not mutagenic and genotoxic, and it protects Salmonella typhimurium cells better than the well-known antioxidant trolox.     

Cyclic oxidation and reduction of protein methionine residues is an important antioxidant mechanism

Almost all forms of reactive oxygen species (ROS) oxidize methionine residues of proteins to a mixture of the R- and S-isomers of methionine sulfoxide. Because organisms contain methionine sulfoxide reductases (Msr's) that can catalyze the thioredoxin-dependent reduction of the sulfoxides back to methionine, it was proposed that the cyclic oxidation/reduction of methionine residues might serve as antioxidants to scavenge ROS, and also to facilitate the regulation of critical enzyme activities. We summarize here results of studies showing that organisms possess two different forms of Msr – namely, MsrA that catalyzes reduction of the S-isomer and MsrB that catalyzes the reduction of the R-isomer. Deletion of the msrA gene in mice leads to increased sensitivity to oxidative stress and to a decrease (40%) in the maximum lifespan. This suggests that elimination of both Msr's would have more serious consequences.     

Leaf senescence and activities of the antioxidant enzymes

Senescence is a genetically regulated process that involves decomposition of cellular structures and distribution of the products of this degradation to other plant parts. Reactions involving reactive oxygen species are the intrinsic features of these processes and their role in senescence is suggested. The malfunction of protection against destruction induced by reactive oxygen species could be the starting point of senescence. This article reviews biochemical changes during senescence in relation to reactive oxygen species and changes in antioxidant protection.     

New promising antioxidants based on 2,6-dimethylphenol

Three new sulfur-containing derivatives of 2,6-dimethylphenol were synthesized. Their antioxidative activity, mutagenicity, and genotoxicity were examined by bacterial tests and by calculating the dominant lethal mutations in murine embryonic cells. It was shown that all the compounds synthesized have a marked antioxidative effect and have no genotoxic and mutagenic properties. One of the antioxidants, 4-(3-dodecylthiopropyl)-2,6-dimethylphenol, increases the survival of cells of both the wild-type Escherichia coli strain and bacterial strains defective in the genes of repair enzymes and has a more distinct antioxidative effect than the classic antioxidants α-tocopherol and trolox, increasing the survival of cells devoid of repair enzymes.     

Microcirculation and oxidative stress

The microcirculation is a complex and integrated system, transporting oxygen and nutrients to the cells. The key component of this system is the endothelium, contributing to the local balance between pro and anti-inflammatory mediators, hemostatic balance, as well as vascular permeability and cell proliferation. A constant shear stress maintains vascular endothelium homeostasis while perturbed shear stress leads to changes in secretion of vasodilator and vasoconstrictor agents. Increased oxidative stress is a major pathogenetic mechanism of endothelial dysfunction by decreasing NO bioavailability, promoting inflammation and participating in activation of intracellular signals cascade, so influencing ion channels activation, signal transduction pathways, cytoskeleton remodelling, intercellular communication and ultimately gene expression. Targeting the microvascular inflammation and oxidative stress is a fascinating approach for novel therapies in order to decrease morbidity and mortality of chronic and acute diseases.     

Cell Proliferation and Oxidative Stress

Antioxidants such as mannitol, butylated hydroxytoluene and a-tocopherol enhance the growth of pol-yoma virus transformed and non-transformed BHK-21 cells. In the case of mannitol this is observed even in the absence of added calf serum. In part these effects may operate to protect cellular growth control mechanisms. On the other hand oxidants such as H₂O₂ and t-butyl hydroperoxide can inhibit growth and overall cellular protein synthesis, through mechanisms that are likely to involve radicals. In the case of H₂O₂, the inhibitory effects can nevertheless be reduced by 'prestressing' the cells with mild heat or with H₂O₂ itself.

Paradoxically very low concentrations (10^?8 M) of H₂ 0₂ or t-butyl hydroperoxide can actually stimulate cell growth, even in the absence of serum. These stimulatory effects however do not appear to involve radicals as they are enhanced by inclusion of mannitol or DMSO in the medium.