Kaempferol prevents the activation of complement C3 protein and the generation of reactive A1 astrocytes that mediate rat brain degeneration induced by 3-nitropropionic acid

• Published in: Food and chemical toxicology 2022-06, Vol.164, p.113017-113017, Article 113017
• Main Authors: Lopez-Sanchez, Carmen, Poejo, Joana, Garcia-Lopez, Virginio, Salazar, Jairo, Garcia-Martinez, Virginio, Gutierrez-Merino, Carlos
• Format: Article
• Language: English
• Subjects: 3-Nitropropionic acid; adults; amyloid; Amyloid beta-Peptides - metabolism; Amyloid β peptides; animal models; Animals; antioxidants; astrocytes; Astrocytes - metabolism; C3 protein; complement; Complement C3 - metabolism; Corpus Striatum - metabolism; hippocampus; human nutrition; Kaempferol; Kaempferols - metabolism; Kaempferols - pharmacology; neurodegenerative diseases; Nitro Compounds - toxicity; Propionates - pharmacology; proteolysis; Rats; Rats, Wistar; Reactive A1 astrocytes; secretion; toxicology; Wistar rats
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2022.113017

Kaempferol is a natural antioxidant present in vegetables and fruits used in human nutrition. In previous work, we showed that intraperitoneal (i.p.) kaempferol administration strongly protects against striatum neurodegeneration induced by i.p. injections of 3-nitropropionic acid (NPA), an animal model of Huntington's disease. Recently, we have shown that reactive A1 astrocytes generation is an early event in the neurodegeneration induced by NPA i.p. injections. In the present work, we have experimentally evaluated the hypothesis that kaempferol protects both against the activation of complement C3 protein and the generation of reactive A1 astrocytes in rat brain striatum and hippocampus. To this end, we have administered NPA and kaempferol i.p. injections to adult Wistar rats following the protocol described in previous work. Kaempferol administration prevents proteolytic activation of complement C3 protein and generation of reactive A1 astrocytes NPA-induced in the striatum and hippocampus. Also, it blocked the NPA-induced increase of NF-κB expression and enhanced secretion of cytokines IL-1α, TNFα, and C1q, which have been linked to the generation of reactive A1 astrocytes. In addition, kaempferol administration prevented the enhanced production of amyloid β peptides in the striatum and hippocampus, a novel finding in NPA-induced brain degeneration found in this work. •Kaempferol prevents the NPA-induced complement C3 protein activation in rat brain.•Kaempferol protects against reactive A1 astrocytes induction by NPA in rat brain.•Kaempferol blocks the NPA-induced increase of IL-1α, TNFα and C1q in rat brain.•Kaempferol prevents the NPA-induced NF-κB expression in striatum and hippocampus.•Kaempferol blocks NPA-induced amyloid β peptides production in striatum and hippocampus.