Alpha-Linolenic Acid Impedes Cadmium-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration in Mouse Brain.
Sayed-Ibrar AlamMin-Woo KimFawad Ali ShahKamran SaeedRahat UllahMyeong-Ok KimPublished in: Cells (2021)
Alpha-Linolenic acid (ALA), an omega-3 polyunsaturated fatty acid, is extracted from plant sources and has been shown to be one of the anti-inflammatory and antioxidant agents. Herein, we revealed the molecular mechanism underlying the anti-inflammatory and antioxidant potential of (ALA), against cadmium in the adult mouse brain. We evaluated the neuroprotective effect of ALA (60 mg/kg per oral for 6 weeks) against CdCl2 (5 mg/kg)-induced oxidative stress, neuroinflammation, and neuronal apoptosis. According to our findings, ALA markedly reduced ROS production and nitric oxide synthase 2 (NOS2) and enhanced the expression of nuclear factor-2 erythroid-2 (Nrf-2) and heme oxygenase-1 (HO-1) in mice treated with CdCl2. Most importantly, the molecular docking study revealed that ALA allosterically decreases the overexpression of c-Jun N-terminal kinase (JNK) activity and inhibited the detrimental effect against CdCl2. Moreover, ALA suppressed CdCl2-induced glial fibrillary acidic protein (GFAP), nuclear factor-kappa b (NF-κB), and interleukin-1β (IL-1β) in the mouse brain. Further, we also checked the pro- and anti-apoptotic proteins markers such as Bax, Bcl-2, and caspase-3, which were regulated in the cortex of ALA co-treated mouse brain. Overall, our study suggests that oral administration of ALA can impede oxidative stress, neuroinflammation, and increase neuronal apoptosis in the cortex of Cd-injected mouse brain.
Keyphrases
- nuclear factor
- oxidative stress
- anti inflammatory
- cell death
- toll like receptor
- nitric oxide synthase
- molecular docking
- diabetic rats
- induced apoptosis
- fatty acid
- lps induced
- traumatic brain injury
- dna damage
- nitric oxide
- signaling pathway
- cell cycle arrest
- lipopolysaccharide induced
- endoplasmic reticulum stress
- inflammatory response
- hydrogen peroxide
- molecular dynamics simulations
- heavy metals
- single cell
- type diabetes
- newly diagnosed
- blood brain barrier
- skeletal muscle
- drinking water
- spinal cord injury
- pi k akt
- risk assessment
- high glucose
- preterm birth
- young adults
- insulin resistance
- ionic liquid