Sulforaphane Induces Glioprotection After LPS Challenge

• Published in: Cellular and molecular neurobiology 2022-04, Vol.42 (3), p.829-846
• Main Authors: Bobermin, Larissa Daniele, Weber, Fernanda Becker, dos Santos, Tiago Marcon, Belló-Klein, Adriane, Wyse, Angela T. S., Gonçalves, Carlos-Alberto, Quincozes-Santos, André
• Format: Article
• Language: English
• Subjects: Adenosine receptors; Animals; Antioxidants; Astrocytes; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cells, Cultured; Central nervous system; Glial cell line-derived neurotrophic factor; Glutamate-ammonia ligase; Glutamine; Glutathione; Heme; Heme oxygenase (decyclizing); Homeostasis; Hypoxia-inducible factors; Inflammation; Isothiocyanates - pharmacology; Lipopolysaccharides; Lipopolysaccharides - pharmacology; mRNA; Na+/K+-exchanging ATPase; NAD(P)H oxidase; Neurobiology; Neuronal-glial interactions; Neurosciences; NF-E2-Related Factor 2 - metabolism; Nitrotyrosine; Original Research; Oxygenase; Rats; S100b protein; Signal Transduction; Sulforaphane; Sulfoxides; Superoxide dismutase
• ISSN: 0272-4340; 1573-6830
• DOI: 10.1007/s10571-020-00981-5

Sulforaphane is a natural compound that presents anti-inflammatory and antioxidant properties, including in the central nervous system (CNS). Astroglial cells are involved in several functions to maintain brain homeostasis, actively participating in the inflammatory response and antioxidant defense systems. We, herein, investigated the potential mechanisms involved in the glioprotective effects of sulforaphane in the C6 astrocyte cell line, when challenged with the inflammogen, lipopolysaccharide (LPS). Sulforaphane prevented the LPS-induced increase in the expression and/or release of pro-inflammatory mediators, possibly due to nuclear factor κB and hypoxia-inducible factor-1α activation. Sulforaphane also modulated the expressions of the Toll-like and adenosine receptors, which often mediate inflammatory processes induced by LPS. Additionally, sulforaphane increased the mRNA levels of nuclear factor erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO1), both of which mediate several cytoprotective responses. Sulforaphane also prevented the increase in NADPH oxidase activity and the elevations of superoxide and 3-nitrotyrosine that were stimulated by LPS. In addition, sulforaphane and LPS modulated superoxide dismutase activity and glutathione metabolism. Interestingly, the anti-inflammatory and antioxidant effects of sulforaphane were blocked by HO1 pharmacological inhibition, suggesting its dependence on HO1 activity. Finally, in support of a glioprotective role, sulforaphane prevented the LPS-induced decrease in glutamate uptake, glutamine synthetase activity, and glial-derived neurotrophic factor (GDNF) levels, as well as the augmentations in S100B release and Na + , K + ATPase activity. To our knowledge, this is the first study that has comprehensively explored the glioprotective effects of sulforaphane on astroglial cells, reinforcing the beneficial effects of sulforaphane on astroglial functionality.