J Korean Geriatr Soc.  2012 Dec;16(4):206-216. 10.4235/jkgs.2012.16.4.206.

Protective Effects of Fenofibrate Against the Inflammatory Cytokines in Lipopolysaccharide-Induced Mice Brain Tissues

• Park HW
• Yoo SJ
• Park JH

• KMID: 2188293
• DOI: http://doi.org/10.4235/jkgs.2012.16.4.206

Abstract

BACKGROUND
Increasing evidence suggests that the entry of proinflammatory factors into the brain induces the activation of microglia, astrocytes, and oligodendrocytes and then produces the more proinflammatory cytokines and reactive oxygen species that can ultimately lead to neuronal death. This has clinical implications and provides a link between periperal inflammation and neuroinflammation. Peroxisome proliferator-activated receptors (PPARs), a member of the nuclear hormone receptor superfamily, has been implicated in the regulation of immunity and inflammation in rodents and humans. The objective of this study was to investigate whether the increased expression of PPAR with fenofibrate treatment was altered in the immune system of mice brain tissue after Lipopolysaccharide (LPS) was injected intraperitoneally.
METHODS
PPARs expression was investigated in the brain tissues of BalB/c mice (n=6) under four situationssterile saline injection (control), LPS injection to generate periperal inflammation, LPS injection (5 mg/kg) with pretreated fenofibrate, and fenofibrate injection (100 mg/kg).
RESULTS
Fenofibrate has protective effects against the increase of LPS-induced proinflammatory cytokines including interleukin (IL)-1beta, IL-6, and tumer necrosis factor-alpha in serum and brain tissue, measured using the enzyme linked immunosorbent assay, reverse transcriptase-polymerase chain reaction, and Western blot analysis. Also fenofibrate pretreatment markedly suppressed the reduction of PPARs mRNA and protein level by LPS injection. Moreover, the increased activation of PPARs abrogated the reduction of ABCD3, ACOX1, and catalase expression leading to an increase in the antioxidative capacity in brain tissue blocking the production of lipid peroxidation after LPS administration.
CONCLUSION
The antiinflammatory and antioxidative properties of fenofibrate may be useful in ameliorating the progression of neuronal diseases.

Keyword

Fenofibrate; Lipopolysaccharide; Cytokine; Peroxisome proliferator-activated receptors

MeSH Terms

Aluminum Hydroxide
Animals
Astrocytes
Blotting, Western
Brain
Carbonates
Catalase
Cytokines
Enzyme-Linked Immunosorbent Assay
Fenofibrate
Humans
Immune System
Inflammation
Interleukin-6
Interleukins
Lipid Peroxidation
Mice
Microglia
Necrosis
Neurons
Oligodendroglia
Peroxisome Proliferator-Activated Receptors
Reactive Oxygen Species
RNA, Messenger
Rodentia
Aluminum Hydroxide
Carbonates
Catalase
Cytokines
Fenofibrate
Interleukin-6
Interleukins
Peroxisome Proliferator-Activated Receptors
RNA, Messenger
Reactive Oxygen Species