No abstract

α-Lipoic acid administration activates a coordinated cytoprotective response against diabetes-induced oxidative injury in kidney tissue through an O-GlcNAc-dependent mechanism.

Pancreatic b-cell death or dysfunction mediated by oxidative stress underlies the development and progression of diabetes mellitus. In the present study, we tested extracts from the edible mushroom Lactarius deterrimus and the chestnut Castanea sativa, as well as their mixture (MIX Ld/Cs), for potential beneficial effects on streptozotocin (STZ)-induced pancreatic b-cell death. Analysis of chelating effects, reducing power and radical-scavenging assays revealed strong antioxidant effects of the C. sativa extract and MIX Ld/Cs, while the L. deterrimus extract displayed a weak to moderate effect. The antioxidative effect of the chestnut extract corresponds with the high content of phenolics and flavonoids identified by HPLC analysis. In contrast, the mushroom extract contains relatively small amounts of phenols and flavonoids. However, both extracts, and especially their combination MIX Ld/Cs, increased cell viability after the STZ treatment as a result of a significant reduction of DNA damage and improved redox status. The chestnut extract and MIX Ld/Cs significantly lowered the STZ-induced increases in superoxide dismutase and catalase activities, while the mushroom extract had no impact on the activities of these antioxidant enzymes. However, the L. deterrimus extract exhibited good NO-scavenging activity. Different mechanisms that underlie antioxidant effects of the mushroom and chestnut extracts were discussed. When combined as in the MIX Ld/Cs, the extracts exhibited diverse but synergistic actions that ultimately exerted beneficial and protective effects against STZ-induced pancreatic b-cell death.Key words: Lactarius deterrimus: Castanea sativa: Rin-5F cells: Cytoprotection: Antioxidant activity Reactive oxygen (ROS) and nitrogen (RNS) species are products of normal aerobic metabolism and are continuously produced under physiological conditions. However, when they rise above their physiological concentrations, ROS and RNS are extremely toxic due to their ability to induce protein and DNA damage and lipid peroxidation. Consequently, organisms have developed antioxidant defence systems, i.e. antioxidative enzymes that work in synergy with nonenzymatic antioxidant systems that are produced in cells or ingested through the diet. In healthy individuals, there is a balance between ROS and RNS production and antioxidant defences. An imbalance provoked by either overproduction of reactive species or attenuation of the antioxidative system leads to a process called oxidative stress. Oxidative stress is implicated in the development of many diseases such as CVD, atherosclerosis, neurodegenerative diseases and diabetes mellitus (1) . Diabetes mellitus is a chronic metabolic disorder that continues to present a major health problem worldwide. It is characterised by hyperglycaemia resulting from deficiencies in insulin secretion, insulin action or both. Multiple biochemical pathways and mechanisms for glucose toxicity have been (2) . All of these pathways have in common the formation of ROS that when in excess...

Chlamydia trachomatis (Ct) can induce scarring disease of the ocular mucosa, known as trachoma, the most common infectious cause of blindness worldwide. We hypothesized that epithelial-mesenchymal transition (EMT) contributes to the fibrotic process in trachomatous scarring. Infection of human conjunctival epithelial cells (HCjE) with Ct activated signaling pathways involved in EMT induction, which was correlated with decreased expression of E-cadherin, guardian of the epithelial phenotype. In addition, Ct infection was associated with increased expression of two mesenchymal cell markers: fibronectin and α-SMA. The DNA methylation statuses of selected regions of E-cadherin, fibronectin, and α-SMA genes revealed that Ct infection was accompanied with changes in DNA methylation of the E-cadherin promoter, while the expression of the two mesenchymal markers was not related with this epigenetic event. Our data suggest that Ct infection of conjunctival epithelial cells induces EMT-like changes that go along with modification of the methylation profile of the E-cadherin promoter and could, as one of the earliest events, contribute to processes triggering conjunctival scarring.

No abstract