Nitrooxidative Stress and Neuroinflammation Caused by Air Pollutants Are Associated with the Biological Markers of Neurodegenerative Diseases.

Millions of people around the world are exposed to air pollutants, such as particulate matter 2.5 (PM2.5) and ozone (O3). Such exposure usually does not exclude these two types of pollutants and their harmful effects could be additive or synergistic. O3 is a highly oxidizing gas that reacts with the cellular environment just as PM2.5, triggering nitrooxidative damage. Once nitrooxidative stress overcomes the endogenous antioxidant system, an acute neuroinflammatory process is generated, and once it becomes chronic, it favors the formation of neurodegenerative disease markers. The presence of these markers becomes potentially dangerous in people who have a genetic predisposition and are at a higher risk of developing neurodegenerative diseases such as Alzheimer's and Parkinson's. Our experimental approach for nitrooxidative damage and neuroinflammation caused by air pollutants has focused on the exposure of rats to O3 in an isolated chamber. The hippocampus is the most studied brain structure because of its neuronal connectivity network with the olfactory epithelium, its weak antioxidant defense, and its fundamental roll in cognitive processes. However, other brain structures may exhibit a different degree of damage upon exposure to O3 and PM2.5, making their involvement an important factor in developing other CNS diseases. The age spectrum for augmented sensibility to air pollutants seems to mostly affect the pre-postnatal (autism spectrum) period and the elderly (neurodegenerative). Thus, a new approach could be the estimation of the damage caused by PM2.5 and O3 through a controlled exposure paradigm to determine the extent of damage caused by both pollutants.

Curcumin Modifies the Activity of Plasmatic Antioxidant Enzymes and the Hippocampal Oxidative Profile in Rats upon Acute and Chronic Exposure to Ozone.

Ozone (O3) is an oxidating tropospheric pollutant. When O3 interacts with biological substrates, reactive oxygen and nitrogen species (RONS) are formed. Severe oxidative damage exhausts the endogenous antioxidant system, which leads to the decreased activity of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Curcumin (CUR) is a natural polyphenol with well-documented antioxidant and anti-inflammatory properties. The aim of this work is to evaluate the effects of curcumin on CAT, GPx, and SOD activity and the inhibition of oxidative damage after the acute and chronic exposure to O3. Fifty male Wistar rats were divided into five experimental groups: the intact control, CUR-fed control, exposed-to-O3 control, CUR-fed (preventive), and CUR-fed (therapeutic) groups. These two last groups received a CUR-supplemented diet while exposed to O3. These experiments were performed during acute- and chronic-exposure phases. In the preventive and therapeutic groups, the activity of plasma CAT, GPx, and SOD was increased during both exposure phases, with slight differences; concomitantly, lipid peroxidation and protein carbonylation were inhibited. For this reason, we propose that CUR could be used to enhance the activity of the antioxidant system and to diminish the oxidative damage caused by exposure to O3.

Curcumin Decreases Hippocampal Neurodegeneration and Nitro-Oxidative Damage to Plasma Proteins and Lipids Caused by Short-Term Exposure to Ozone.

Neurodegeneration is the consequence of harmful events affecting the nervous system that lead to neuronal death. Toxic substances, including air pollutants, are capable of inducing neurodegeneration. Ozone (O3) is the most oxidative toxic pollutant. O3 reacts with cellular components and forms reactive oxygen and nitrogen species, triggering nitro-oxidative damage during short-term exposure. Curcumin (CUR) is a natural phenolic molecule bearing well-documented antioxidant and anti-inflammatory biological activities in diverse experimental models. The aim of this work was to evaluate the effect of preventive dietary administration of CUR against hippocampal neurodegeneration and nitro-oxidative damage caused by short-term exposure to O3. Eighty Wistar male rats were distributed into four experimental groups, twenty rats each: intact control; CUR dietary supplementation without O3 exposure; exposure to 0.7 ppm of O3; and exposed to O3 with CUR dietary supplementation. Five rats from each group were sacrificed at 1, 2, 4, and 8 h of exposure. The CUR dose was 5.6 mg/kg and adjusted according to food consumption. CUR significantly decreased oxidative damage to plasma lipids and proteins, as well as neurodegeneration in CA1 and CA3 hippocampal regions. Concluding, CUR proved effective protection in decreasing neurodegeneration in the hippocampus and prevented systemic oxidative damage.

Dietary Curcumin Prevented Astrocytosis, Microgliosis, and Apoptosis Caused by Acute and Chronic Exposure to Ozone.

Ozone is the most oxidant tropospheric pollutant gas, causing damage through the formation of reactive oxygen and nitrogen species. Reactive species induce the nuclear factor-kappa B (NF-κB) activation leading to neuroinflammation characterized by astrocytosis, microgliosis, and apoptotic cell death. There is interest in evaluating the pharmacological activity of natural antioxidants to confer neuroprotection against the damage caused by ozone in highly polluted cities. Curcumin has been proven to exert a protective action in the central nervous system (CNS) of diverse experimental models, with no side effects. The aim of this work is to evaluate the effect of curcumin in a preventive and therapeutic manner against the astrocytosis, microgliosis, and apoptosis induced by ozone in rat hippocampus. Fifty Wistar rats were distributed into five experimental groups: The intact control, curcumin fed control, ozone-exposed group, and the preventive and therapeutic groups receiving the curcumin supplementation while exposed to ozone. Ozone caused astrocytosis and microgliosis, as well as apoptosis in the hippocampus. Meanwhile, curcumin was able to decrease the activation of microglia and astrocytes, and apoptotic cell death in both periods of exposure. Therefore, we propose that curcumin could be used as a molecule capable of counteracting the damage caused by ozone in the CNS.

Curcumin Exerted Neuroprotection against Ozone-Induced Oxidative Damage and Decreased NF-κB Activation in Rat Hippocampus and Serum Levels of Inflammatory Cytokines.

Ozone is a harmful tropospheric pollutant, causing the formation of reactive oxygen and nitrogen species that lead to oxidative damage in living beings. NF-κB can be activated in response to oxidative damage, inducing an inflammatory response. Nowadays, there are no reliable results that consolidate the use of antioxidants to protect from damage caused by ozone, particularly in highly polluted cities. Curcumin has a strong antioxidant activity and is a potent inhibitor of NF-κB activation with no side effects. The aim of this study is to evaluate the effect of curcumin in preventive and therapeutic approaches against oxidative damage, NF-κB activation, and the rise in serum levels of IL-1ß and TNF-α induced by acute and chronic exposure to ozone in rat hippocampus. One hundred male Wistar rats were distributed into five groups; the intact control, curcumin-fed control, the ozone-exposed group, and the preventive and therapeutic groups. These last two groups were exposed to ozone and received food supplemented with curcumin. Lipid peroxidation was determined by spectrophotometry, and protein oxidation was evaluated by immunodetection of carbonylated proteins and densitometry analysis. Activation of NF-κB was assessed by electrophoretic mobility shift assay (EMSA), and inflammatory cytokines (IL-1ß and TNF-α) were determined by ELISA. Curcumin decreased NF-κB activation and serum levels of inflammatory cytokines as well as protein and lipid oxidation, in both therapeutic and preventive approaches. Curcumin has proven to be a phytodrug against the damage caused by the environmental exposure to ozone.