Oxidative stress is considered to be one of the important etiological factors invarious diseases including gastric ulcers. The mechanism of aspirin induced gastric lesion ismediated through lipid peroxidation. The effects of Cissus quadrangularis extract on aspirin-induced ulceration in rats with respect to its antioxidant status, lipid peroxidation, quantityof mucus and alkaline phosphatase and myeloperoxidase (MPO) activities was estimated.Cissus quadrangularis facilitated the healing of experimental gastric ulcer by increasedmucus content, antioxidant defense enzyme activity and decreased MPO activity and lipidperoxides levels in the gastric mucosa. These results indicate that Cissus quadrangularis extract protects against aspirin-induced gastric mucosal lesions in rats possibly through itsantioxidative action.
The oxidative stress hypothesis of aging is currently one of the most popular explanations for the cause of aging. Oxidative stress, including that due to reactive oxygen species, causes lesions to biomolecules such as DNA, protein and lipids. 8-Oxo-2'-deoxyguanosine (8-oxodG) is a major oxidative product of DNA and can be detected using avariety of assay methods. For an accurate measurement of 8-oxodG, it is important to minimize as much as possible the oxidation of intact DNA during its isolation from cells or tissues and during the hydrolysis of DNA to nucleosides. The most popular analyticaltechnique is high-performance liquid chromatography with electrochemical detection. The levels of oxidative damage to DNA are likely to increase in mammalian tissues during aging, although it is not clear whether the levels increase linearly during aging or exponentially in aged animals. The accumulation of oxidative damage to DNA is recognized asinducing mutations and dysfunction during aging. The steady state levels of oxidative damage to DNA are proposed to depend on the balance between the formation and repair of damage. The repair activity appears to be weak in aged animals compared with young animals, but antioxidative activity has not been shown to undergo a consistent changing pattern.Thus, it is assumed that the decline in repair activity in aged animals leads to the accumulation of oxidative damage in aged tissues.
The nematode Caenorhabditis elegans has proven a robust genetic model for studies of aging and the roles of oxidative stress. In this review we focus on the genetics of select long-lived and short-lived mutants of C. elegans that have proven useful in revealing the relationships that exist between oxidative stress and life span. The former are known to be controlled by an insulin/insulin-like growth factor (IGF-1)-like pathway, while the latter are affected by mitochondrial functions.
The oxidative stress theory of aging has become increasingly accepted as explaining at least in part the aging process. In mammalian genetic models of aging, a genetic deficiency of the p66-shc gene, which encodes a phosphotyrosine signal adapter protein, extends life span by 30% in mice, and confers resistance to oxidative stress. Upon oxidative stress, p66-Shc is phosphorylated at Ser36, contributing to inactivation of the forkhead- type transcription factor (FKHR), which regulates the gene expression of cellular antioxidants. The p66-Shc signaling has a direct connection with the evolutionary conserved longevity-related signaling, involving FKHR located far downstream of the insulinlike growth factor receptor and phosphatidyl inositol 3-kinase. While Shc is a mostly constitutive protein, it is not expressed in mature neurons of the adult brain. Instead, two neurally expressed homologues, Sck/ShcB and N-Shc/ShcC, take over the roles of Shc. N-Shc has long and short isoforms, p68 and p52, and seems to be phosphorylated at several serine residues under oxidative stress conditions, suggesting that it too has a role in oxidative stress and brain aging. The expression of Shc-related genes is affected in aging, though only slightly, which may be relevant to cellular dysfunction and/or death during aging.
The fruit fly, Drosophila melanogaster, is an excellent model system for the study of complex biological processes including aging. Through genetic manipulation of antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, the roles of these enzymes in oxidative stress resistance and life span determination were established. Transgenic flies overexpressing the enzyme peptide methionine sulfoxide reductase A (MSRA) have been shown to live longer and are more resistant to paraquat-induced oxidative stress. It has been also demonstrated that mutations in genes involved in the insulin/insulin-like growth factor (IGF) pathway (IGF receptor, chico, d FOXO) affected life span and sensitivity to various stresses. We have conducted a conditional gene misexpression screen to identify genes, whose overexpression in adult stages extends life span. Among 13 genes whose functions are known or suggested, six genes were found to be related to stress resistance or redox balance (Dm GST2, hsp26, sra, and Drosophila homologs of mammalian TRX, GILT, and POSH). We recently established a method for the efficient measurement of oxidative stress resistance in Drosophila, using a commercially available activity monitor. The method is suitable for the screening of oxidative stress resistance-related genes using a large number of mutagenized fly lines.