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and reduced the levels of p-p65, p-IB, p-p38, and p-ERK1/2, which reduced the levels of prefrontal cortex proinflammatory cytokines, such as IL-1, TNF, IL-6, COX-2 and iNOS levels by activating the NRF-2 signalling pathway and inhibiting the MAPK and NF-kB signalling pathways to reduce inflammation, reduce oxidative stress, and improve schizophrenia-like behaviour ( 7.6 Chronic cerebral hypoperfusion Chronic cerebral hypoperfusion induces the activation of inflammasome components in distinct brain regions

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Figure 3 Locally produced melatonin also protects the intramitochondrial environment from oxidative stress since in addition to acting as a direct radical scavenger it also stimulates enzymes, i.e., superoxide dismutase 2 (SOD2) and glutathione peroxidase (GPx), that remove ROS from the mitochondrial matrix (103)

Finally, cluster 8 was the most crowded (24 metabolites) and was composed by metabolites which abundance mainly increased in the deceased group

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