Lipoic Acid and Fish Oil Combination Potentiates Neuroinflammation and Oxidative Stress Regulation and Prevents Cognitive Decline of Rats After Sepsis.

Abstract

Sepsis causes organ dysfunction due to an infection, and it may impact the central nervous system. Neuroinflammation and oxidative stress are related to brain dysfunction after sepsis. Both processes affect microglia activation, neurotrophin production, and long-term cognition. Fish oil (FO) is an anti-inflammatory compound, and lipoic acid (LA) is a universal antioxidant substance. They exert neuroprotective roles when administered alone. We aimed at determining the effect of FO+LA combination on microglia activation and brain dysfunction after sepsis. Microglia cells from neonatal pups were co-treated with lipopolysaccharide (LPS) and FO or LA, alone or combined, for 24 h. Cytokine levels were measured. Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) and treated orally with FO, LA, or FO+LA. At 24 h after surgery, the hippocampus, prefrontal cortex, and total cortex were obtained and assayed for levels of cytokines, myeloperoxidase (MPO) activity, protein carbonyls, superoxide dismutase (SOD), and catalase (CAT) activity. At 10 days after surgery, brain-derived neurotrophic factor (BDNF) levels were determined and behavioral tests were performed. The combination diminished in vitro levels of pro-inflammatory cytokines. The combination reduced TNF-α in the cortex, IL-1β in the prefrontal cortex, as well as MPO activity, and decreased protein carbonyls formation in all structures. The combination enhanced catalase activity in the prefrontal cortex and hippocampus, elevated BDNF levels in all structures, and prevented behavioral impairment. In summary, the combination was effective in preventing cognitive damage by reducing neuroinflammation and oxidative stress and increasing BDNF levels.

• Authors: Amanda Della Giustina, Mariana Pereira de Souza Goldim, Lucinéia Gainski Danielski, Leandro Garbossa, Aloir Neri Oliveira Junior, Thainá Cidreira, Taís Denicol, Sandra Bonfante, Naiana da Rosa, Jucélia Jeremias Fortunato, Juliete Palandi, Bruna Hoffmann de Oliveira, Daniel Fernandes Martins, Franciane Bobinski, Michelle Garcez, Tatiani Bellettini-Santos, Josiane Budni, Gabriela Colpo, Giselli Scaini, Vijayasree V Giridharan, Tatiana Barichello, Fabricia Petronilho
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 57 Issue 11 Pg. 4451-4466 (Nov 2020) ISSN: 1559-1182 [Electronic] United States
• PMID: 32743736 (Publication Type: Journal Article)

Chemical References

• Brain-Derived Neurotrophic Factor
• Cytokines
• Fish Oils
• Thioctic Acid
• Catalase
• Peroxidase
• Superoxide Dismutase

Topics

• Animals
• Brain (drug effects, pathology)
• Brain-Derived Neurotrophic Factor (metabolism)
• Catalase (metabolism)
• Cells, Cultured
• Cognitive Dysfunction (etiology, prevention & control)
• Cytokines (metabolism)
• Female
• Fish Oils (pharmacology)
• Inflammation (complications, pathology)
• Kaplan-Meier Estimate
• Memory Disorders (complications)
• Microglia (drug effects, metabolism)
• Open Field Test
• Oxidative Stress (drug effects)
• Peroxidase (metabolism)
• Protein Carbonylation (drug effects)
• Rats, Wistar
• Sepsis (complications)
• Superoxide Dismutase (metabolism)
• Thioctic Acid (pharmacology)