Taurine as a Natural Antioxidant: From Direct Antioxidant Effects to Protective Action in Various Toxicological Models

Natural antioxidants have received tremendous attention over the last 3 decades. At the same time, the attitude to free radicals is slowly changing, and their signalling role in adaptation to stress has recently received a lot of attention. Among many different antioxidants in the body, taurine (Tau), a sulphur-containing non-proteinogenic β-amino acid, is shown to have a special place as an important natural modulator of the antioxidant defence networks. Indeed, Tau is synthesised in most mammals and birds, and the Tau requirement is met by both synthesis and food/feed supply. From the analysis of recent data, it could be concluded that the direct antioxidant effect of Tau due to scavenging free radicals is limited and could be expected only in a few mammalian/avian tissues (e.g., heart and eye) with comparatively high (>15–20 mM) Tau concentrations. The stabilising effects of Tau on mitochondria, a prime site of free radical formation, are characterised and deserve more attention. Tau deficiency has been shown to compromise the electron transport chain in mitochondria and significantly increase free radical production. It seems likely that by maintaining the optimal Tau status of mitochondria, it is possible to control free radical production. Tau’s antioxidant protective action is of great importance in various stress conditions in human life, and is related to commercial animal and poultry production. In various in vitro and in vivo toxicological models, Tau showed AO protective effects. The membrane-stabilizing effects, inhibiting effects on ROS-producing enzymes, as well as the indirect AO effects of Tau via redox balance maintenance associated with the modulation of various transcription factors (e.g., Nrf2 and NF-κB) and vitagenes could also contribute to its protective action in stress conditions, and thus deserve more attention.

Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

Background Alzheimer’s disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD. Objectives AD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease. Results We show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation. Conclusion Our data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention.

Inhibitory Action of Antidiabetic Drugs on the Free Radical Production by the Rod Outer Segment Ectopic Aerobic Metabolism

Rod outer segments (OS) express the FoF1-ATP synthase and the respiratory chain, conducting an ectopic aerobic metabolism that produces free radicals in vitro. Diabetic retinopathy, a leading cause of vision loss, is associated with oxidative stress in the outer retina. Since metformin and glibenclamide, two anti-type 2 diabetes drugs, target the respiratory complexes, we studied the effect of these two drugs, individually or in association, on the free radical production in purified bovine rod OS. ATP synthesis, oxygen consumption, and oxidative stress production were assayed by luminometry, oximetry and flow cytometry, respectively. The expression of FoF1-ATP synthase was studied by immunogold electron microscopy. Metformin had a hormetic effect on the OS complex I and ATP synthetic activities, being stimulatory at concentrations below 1 mM, and inhibitory above. Glibenclamide inhibited complexes I and III, as well as ATP production in a concentration-dependent manner. Maximal concentrations of both drugs inhibited the ROI production by the light-exposed OS. Data, consistent with the delaying effect of these drugs on the onset of diabetic retinopathy, suggest that a combination of the two drugs at the beginning of the treatment might reduce the oxidative stress production helping the endogenous antioxidant defences in avoiding retinal damage.