Alpha-Linolenic Acid Impedes Cadmium-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration in Mouse Brain

Cells

Fawad Ali Shah¹  Sayed-Ibrar Alam²  Min-Woo Kim²  Rahat Ullah²  Kamran Saeed²  Myeong-Ok Kim² 

[1] Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan;Division of Life Sciences and Applied Life Science (BK 21 PLUS), College of Natural Science, Gyeongsang National University, Jinju 52828, Korea;

关键词: cadmium;    reactive oxygen species (ROS);    Nrf2/HO-1;    neuroinflammation;    neurodegeneration;    p-JNK;   

DOI  :  10.3390/cells10092274

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown