Aluminium is known to accelerate oxidative stress, amyloid beta (Aβ) deposition, and plaque formation in the brain of rats.Objective. The present study is aimed at studying the neuroprotective effects of eugenol following aluminium-induced neurotoxicity on caspase-3, apoptotic proteins (Bcl-2 and Bax), and oxidative stress markers in Wistar rats such as superoxide dismutase (SOD), glutathione peroxidase (GPx), nitric oxide (NO), and assay oxidative stress to mitochondrial DNA (mtDNA) by measuring the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG).Materials and methods. Twenty (20) adult Wistar rats were randomly divided into four (4) groups with five animals in each group. Route of administration was oral throughout the duration of this study and this study lasted for 21 days. Rats were sacrificed 24 hours after administration of the last dose (i.e., day 22) with 0.8 mg/kg ketamine as an anaesthetic agent.Results. Exposure to AlCl₃resulted in a significant (p<0.01) elevation in the levels of nitric oxide and 8-hydroxy-2-deoxyguanosine (8-OHdG), enhanced the activity of caspase-3, increased the level of proapoptotic protein Bax and reduced the levels of antiapoptotic protein Bcl-2, and significantly (p<0.01) reduced the levels of SOD and GPx. However, treatment with eugenol resulted in a significant reduction (p<0.01) in the levels of nitric oxide (NO) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, inhibited the activity of caspase-3, increased levels of Bcl-2 and significantly (p<0.05) reduced levels of Bax protein, respectively, and also significantly (p<0.05) increased the levels of SOD and GPx. Our results would hereby suggest that eugenol would provide a therapeutic value against aluminium-induced oxidative stress as related to antioxidant and antiapoptotic activities.

Aluminium and its compounds when taken orally can have negative impacts on a variety of enzymes leading to neurotoxicity. Apurinic endonuclease 1 (APE-1), a protein that performs multiple functions, including deoxyribonucleic acid (DNA) repair, is essential for cell survival. Thus, the determination of APE-1 with aluminium chloride (AlCl3) induced neuro-inflammation in Wistar rats was performed in this study. Wistar rats were divided into four groups, each with six animals. Group 1 received 100 mg/kg AlCl3 orally, Group 2 received 150 mg/kg eugenol, Group 3 received both 100 mg/kg AlCl3 and 150 mg/kg eugenol, and Group 4 received 0.8 ml/kg distilled water. Rats were euthanized after eight weeks, and brain tissues were homogenized and analysed. Oral administration of AlCl3 resulted in significant (p<0.01) decreased APE-1, superoxide dismutase (SOD) and amyloid beta-40 (Aβ-40), and significant (p<0.01) increased tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1), inducible nitric oxide synthase (iNOS), myeloperoxidase, and nitric oxide (NO). Co-administration of AlCl3 and eugenol significantly increased (p<0.01) APE-1, Aβ-40 and SOD, while significantly decreasing (p<0.01) TNF-α, IL-1, iNOS and MPO levels. Our findings suggest that eugenol, by targeting these most potent hallmarks of neurodegeneration could be an effective alternative in its treatment.

Cadmium neurotoxicity is associated with oxidative injury, impaired antioxidant defence and dysregulated apoptosis-associated signalling. This study investigated whether dimethyl fumarate (DMF) attenuates cadmium chloride (CdCl₂)-induced biochemical injury in the hippocampus and prefrontal cortex of male Wistar rats. Thirty-two rats were randomly allocated to Control, CdCl₂ (5 mg/kg/day), DMF (25 mg/kg/day) and CdCl₂+DMF groups (n = 8/group) and treated orally for 30 days. Malondialdehyde (MDA), total nitrate/nitrite (NOx), 8-hydroxy-2′-deoxyguanosine (8-OHdG), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), reduced glutathione (GSH), PUMA, caspase-3, BAX and BCL-2 were assessed in both regions. CdCl₂ increased MDA, NOx, 8-OHdG, PUMA, caspase-3 and BAX, reduced SOD, catalase, GPx, GSH and BCL-2, and markedly increased the BAX/BCL-2 ratio. DMF co-treatment significantly attenuated these alterations. Hippocampal PUMA increased from 1.00 ± 0.18 to 2.48 ± 0.42-fold of Control and was reduced to 1.39 ± 0.25 by DMF, while the BAX/BCL-2 ratio fell from 5.76 ± 1.36 to 1.86 ± 0.45. Comparable protection occurred in the prefrontal cortex. These findings support DMF-mediated biochemical neuroprotection associated with restored antioxidant defence and attenuation of PUMA/BCL-2-family-associated pro-apoptotic signalling, although recovery of selected oxidative and hippocampal apoptosis-associated endpoints remained incomplete overall.

Cadmium disrupts neuronal redox control and mitochondrial energy production, but whether dimethyl fumarate (DMF) protects the brain mainly through NRF2 remains uncertain. Adult male Wistar rats were assigned to control, cadmium, DMF, ML385, cadmium plus DMF, cadmium plus ML385, or cadmium plus DMF plus ML385 groups (n = 12/group). Cadmium chloride (5 mg/kg) and DMF (25 mg/kg) were administered orally, while ML385 (30 mg/kg) was given intraperitoneally, daily for 30 days. Brain cadmium, NRF2 binding to antioxidant response elements in the Nqo1 and Gclc promoters, NQO1, GCLC and TXNRD1 abundance, glutathione status, F₂-isoprostanes, mitochondrial respiration, ATP and Y-maze performance were assessed. Cadmium suppressed NRF2 promoter binding and target proteins, shifted glutathione towards oxidation, increased F₂-isoprostanes, impaired mitochondrial respiration, depleted ATP and reduced spontaneous alternation. DMF improved all these outcomes without significantly lowering hippocampal cadmium (3.85 ± 0.24 versus 3.62 ± 0.22 µg/g; adjusted P = 0.975). Adding ML385 to cadmium plus DMF reduced NRF2 occupancy at the Nqo1 promoter from 1.28 ± 0.09 to 0.62 ± 0.05% input and lowered the GSH/GSSG ratio from 12.26 ± 1.76 to 5.46 ± 0.56. It also reduced oxidative phosphorylation from 56 ± 3 to 40 ± 2.5 pmol O₂/s/mg and spontaneous alternation from 61 ± 2.5% to 48 ± 2.4% (all adjusted P ≤ 0.003), without a significant difference in total arm entries. Several outcomes nevertheless remained partly improved. These findings support a major, although not exclusive, contribution of NRF2 signalling to DMF-mediated redox, mitochondrial and cognitive protection during cadmium exposure in rats.