Oxidative Stress Caused by Ozone Exposure Induces Changes in P2X7 Receptors, Neuroinflammation, and Neurodegeneration in the Rat Hippocampus.

Low-ozone doses cause alterations in the oxidation-reduction mechanisms due to the increase in reactive oxygen species, alter cell signaling, and produce deleterious metabolic responses for cells. Adenosine 5'triphosphate (ATP) can act as a mediator in intercellular communication between neurons and glial cells. When there is an increase in extracellular ATP, a modification is promoted in the regulation of inflammation, energy metabolism, by affecting the intracellular signaling pathways that participate in these processes. The objective of this work was to study changes in the P2X7 receptor, and their relationship with the inflammatory response and energy metabolism, in a model of progressive neurodegeneration in the hippocampus of rats chronically exposed to low-ozone doses. Therefore, 72 male rats were exposed to low-ozone doses for different periods of time. After exposure to ozone was finished, rats were processed for immunohistochemical techniques, western blot, quantitative polymerase chain reaction (qPCR), and histological techniques for periodic acid-Schiff staining. The results showed immunoreactivity changes in the amount of the P2X7 protein. There was an increase in phosphorylation for glycogen synthase kinase 3-ß (GSK3-ß) as treatment continued. There were also increases in 27 interleukin 1 beta (IL-1 ß) and interleukin 17 (IL-17) and a decrease in interleukin 10 (IL-10). Furthermore, neuronal glycogen was found at 30 and 60 days, and an increase in caspase 3. An increase in mRNA was also shown for the P2X7 gene at 60 days, and GSK3-ß at 90 days of exposure. In conclusion, these results suggest that repeated exposure to low-ozone doses, such as those that can occur during highly polluted days, causes a state of oxidative stress, leading to alterations in the P2X7 receptors, which promote changes in the activation of signaling pathways for inflammatory processes and cell death, converging at a progressive neurodegeneration process, as may be happening in Alzheimer's disease.

Obesity, Oxidative Stress, and Their Effect on Serum Heme Oxygenase-1 Concentrations and Insulin in Children Aged 3 to 5 Years in a Pediatric Hospital of the Ministry of Health CDMX.

BACKGROUND: Obesity during early stages of life may condition states of oxidative stress. Heme oxygenase-1 (HO-1) is an enzyme involved in oxidative metabolism; it has antioxidant and anti-inflammatory functions and is related in sensitivity to insulin. However, a high concentration of this enzyme has been described to cause alterations such as insulin resistance. The objective of this work was to study the relationship between obesity, oxidative stress, HO-1, and insulin in children aged 3 to 5 years. METHODS: To achieve our objective, we studied a control group of children (n = 50) and a group of obese children (n = 50) who underwent an anthropometric evaluation. Additionally, we quantified peroxidized lipids, oxidized low-density lipoproteins (Ox-LDLs), oxidized and reduced glutathione, HO-1, and insulin. We also calculated the homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-%B, and HOMA-%S indices. According to the data distribution, nonparametric and Spearman's rank correlation coefficient tests were conducted. RESULTS: The results demonstrate that obese children show a statistically relevant increase in BMI/age, serum concentrations of peroxidized lipids, Ox-LDLs, oxidized glutathione, HO-1, and insulin (p < 0.005). In addition, there was an increase in the HOMA-IR and HOMA-%B (p < 0.0001) indices and a decrease of reduced glutathione, as well as a reduction in the HOMA-%S, compared with the children of the control group (p < 0.003). CONCLUSIONS: With the results obtained, we can conclude that obese preschool children show a chronic state of oxidative stress, an increase of HO-1, and an incipient state of insulin resistance. Finally, the increased reactive oxygen species could be one of the leading factors involved in insulin resistance and Ox-LDL increase from the preschool stage.