Perinatal Tobacco Smoke Exposure Increases Vascular Oxidative Stress and Mitochondrial Damage in Non-Human Primates

Epidemiological studies suggest that events occurring during fetal and early childhood development influence disease susceptibility. Similarly, molecular studies in mice have shown that in utero exposure to cardiovascular disease (CVD) risk factors such as environmental tobacco smoke (ETS) increased adult atherogenic susceptibility and mitochondrial damage; however, the molecular effects of similar exposures in primates are not yet known. To determine whether perinatal ETS exposure increased mitochondrial damage, dysfunction and oxidant stress in primates, archived tissues from the non-human primate model Macaca mulatta (M. mulatta) were utilized. M. mulatta were exposed to low levels of ETS (1 mg/m3 total suspended particulates) from gestation (day 40) to early childhood (1 year), and aortic tissues were assessed for oxidized proteins (protein carbonyls), antioxidant activity (SOD), mitochondrial function (cytochrome oxidase), and mitochondrial damage (mitochondrial DNA damage). Results revealed that perinatal ETS exposure resulted in significantly increased oxidative stress, mitochondrial dysfunction and damage which were accompanied by significantly decreased mitochondrial antioxidant capacity and mitochondrial copy number in vascular tissue. Increased mitochondrial damage was also detected in buffy coat tissues in exposed M. mulatta. These studies suggest that perinatal tobacco smoke exposure increases vascular oxidative stress and mitochondrial damage in primates, potentially increasing adult disease susceptibility

The role of redox imbalance in relation to immunological process in adjuvant arthritis

The model of adjuvant arthritis (AA) is well characterized concerning the immunological processes involved. However knowledge on the participation of redox imbalance in the progression of AA is scarce. The link between oxidative stress (OS) and immunological status in arthritis should be more precisely investigated. In our experiments, we focused on AA development in the time domain. AA was induced in rats by a single intradermal injection of Mycobacterium butyricum in incomplete Freund’s adjuvant. All experiments included healthy animals (HC) and arthritic animals not treated. We confirmed that the clinical parameters hind paw volume and body weight became significantly modified starting around day 14 after AA induction and this change was maintained until the end of the experiment (day 28). We obtained a good agreement of clinical parameters with parameters of OS. Measurements of plasmatic protein carbonyls revealed damage of proteins caused by OS. Progression of lipid peroxidation in AA was described by analysis of TBARS, HNE- /MDA-protein adducts and F2 isoprostane levels in plasma. Total antioxidant status analyzed in plasma was decreased significantly in both the acute (day 21) and the subchronic phase (day 28) of AA. Further we focused on evaluating CoQ9 plasmatic levels. The arthritic process increased significantly the level of CoQ9 in comparison to HC. Evidently, the arthritic process stimulates the synthesis of CoQ9 and its transport to plasma. In the model of AA, we observed already on experimental day 7 that AA was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as phorbol myristate acetate stimulated chemiluminescence. As the changes in neutrophils occur before the clinical parameter HPV starts to be increased, for further evaluation of neutrophil functionality we chose experimental day 7. The functionality of peripheral blood neutrophils in AA was described by phagocytosis, oxidative burst and metabolic activity. Both phagocytosis and oxidative burst were increased due to arthritis, and that despite the decreased metabolic activity. Analysis of OS in tissue showed changed GGT activity in spleen and joint homogenate accompanied by increased chemiluminescence. The OS parameters were in close relationship with time profiles of selected cytokines, chemokine MCP-1 and of C-reactive protein levels in plasma. Measurements of the immunoregulatory index in peripheral blood and lipoxygenase tissue activity (lung, liver) were also included. Our observations have evidenced the importance of pharmacological regulation of redox imbalance in arthritis. (VEGA 2/0090/08, COST B35, APVV-51-017905, APVV-21-055205