Polybrominated diphenyl ethers (PBDEs) are synthetic halogen compounds, industrially used as flame retardants in many flammable products. PBDEs are environmentally persistent and bioaccumulative substances that were used from the 1970s and discontinued in the 1990s. PBDEs are present in air, soil, water, and food, where they remain stable for a long time. Chronic exposure to PBDEs is associated with adverse human health effects, including cancer, immunotoxicity, hepatotoxicity, reproductive and metabolic disorders, motor and hormonal impairments, and neurotoxicity, especially in children. It has been demonstrated that PBDE exposure can cause mitochondrial and DNA damage, apoptosis, oxidative stress, epigenetic modifications, and changes in calcium and neurotransmitter levels. Here, we conduct a comprehensive review of the molecular mechanisms of the neurotoxicity of PBDEs using different approaches. We discuss the main neurotransmitter pathways affected by exposure to PBDEs in vitro and in vivo in different mammalian models. Excitatory and inhibitory signaling pathways are the putative target where PBDEs carry out their neurotoxicity. Based on this evidence, environmental PBDEs are considered a risk to human public health and a hazard to biota, underscoring the need for environmental monitoring to mitigate exposure to PBDEs.

The epoxyeicosatrienoic acids (EETs) are metabolites that result from the oxidation of the arachidonic acid by cytochrome P450 (CYP) epoxygenases. EETs are known to exert anti-inflammatory, antioxidant, vasodilatory, pro-angiogenic and anti-apoptotic actions. In the nervous system, EETs have been found to be neuroprotective in different models of neuronal damage. However, the molecular mechanisms responsible for these effects are not yet fully understood. This article seeks to review what is known about the signaling pathways involved in the EETs mediated neuroprotection. The mechanisms responsible for these effects are complex and involve several biological pathways that often crosstalk, including an inhibition of NFκB pathway, the activation of PPARα/γ nuclear receptors, and the activation of the PI3K/Akt pathway, among others. We also review what is known about the production and the biological significance of the epoxyeicosatrienoic acid ethanolamides (EET-EAs) and the epoxyeicosatrienoic acid glycerols (EET-EGs), metabolites that result from the epoxidation of the anandamide (AEA) and 2-arachidonylglycerol (2-AG) by CYP epoxygenases, which show endocannabinoid features.

Epoxyeicosatrienoic acids (EETs), are known to possess potent anti‐inflammatory and antioxidant neuroprotective properties. However, the molecular mechanisms responsible for these effects are not well understood. In this work, we aimed to evaluate the neuroprotective role of EETs in a hemorrhagic stroke model and the possible involvement of PPAR‐α activation in this neuroprotection. Hemorrhagic damage was induced in mice through the intracerebral administration of collagenase VII in the striatum. The neuroprotective effect of EETs was tested in mice by pre‐treatments of 2 h with TPPU, an inhibitor of the EETs metabolism. TPPU was administered intraperitoneally at a dose of 0.5, 1.0, or 2 mg/kg. Brain damage was evaluated based on measurements of motor activity, hematoma volume, brain water content, and blood–brain barrier (BBB) permeability. Additionally, the levels of enzymes involved in the oxidative stress balance, such as NADPH oxidase 2 (NOX‐2) and superoxide dismutase (SOD), were determined by Western blot analysis. Our results showed that EETs exert neuroprotective effects by significantly decreasing all parameters related to brain damage, improving motor function and promoting an antioxidant state, as evidenced by increased levels of SOD and reduced levels of NOX enzymes. Subsequently, PPAR‐α involvement was evaluated through the administration of GW6471, a PPAR‐α antagonist. Pre‐treating mice with GW6471 for 30 min, reverted all neuroprotective effects, including the observed changes in SOD and NOX levels. Our results demonstrate that EETs confer neuroprotection in hemorrhagic brain injury, and this effect is dependent on PPAR‐α activation.

Monosodium glutamate (MSG), a flavor enhancer, and butylated hydroxyanisole (BHA), an antioxidant, are among the most widely used additives worldwide. The present study aims to investigate the inflammatory effect of oral administration of MSG (40 mg/kg body weight) and BHA (0.5 mg/kg body weight) for 28 days, by evaluating proinflammatory cytokines in serum and NF-κB, Nrf2, CYP2C11, and CYP2J3 gene and protein expression in liver and cerebral cortex in male Wistar rats. Additionally, one group of rats was intraperitoneally injected with lipopolysaccharide (LPS) to induce systemic inflammation. The administration of MSG significantly increased serum levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) and NF-κB gene expression in the liver and cortex. Also, the protein levels of the p65-NFkb subunit increased in cytosolic fraction in liver and Nrf2 transcription factor increased in the nuclear fraction in both the liver and cortex. Although we found that CYP2C11 and CYP2J3 mRNA levels were increased by MSG in the liver and cortex, no differences in protein levels were observed compared to controls. In contrast, BHA consumption did not cause inflammation or oxidative stress. Taken together, our findings suggest that MSG consumption induces systemic inflammation and oxidative stress under the evaluated conditions.

Neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), represent a critical global health challenge characterized by the progressive and currently irreversible loss of neuronal function. A key pathogenic factor in these diverse conditions is the disruption of redox balance, in which excessive reactive oxygen species (ROS) overwhelm the body’s natural antioxidant defenses. Neurons are particularly susceptible to this oxidative stress due to their high oxygen consumption, high lipid content, and limited regenerative capacity. This imbalance leads to a cascade of cellular damage, including lipid peroxidation, protein misfolding, and oxidative DNA lesions. Mitochondrial dysfunction serves as both a primary source and a major target of ROS, leading to bioenergetic failure and activation of apoptotic pathways. Furthermore, a self-perpetuating cycle of neuroinflammation and oxidative stress, driven largely by microglial activation, accelerates tissue damage. This chapter discusses the key cellular and molecular mechanisms involved in oxidative stress in neurodegenerative pathologies and explores its biomarkers and therapeutic strategies. Understanding oxidative stress molecular mechanisms, along with the roles of protective targets, is essential for identifying therapeutic opportunities to regulate neurodegeneration.