Simvastatin prevents the inflammatory process and the dopaminergic degeneration induced by the intranigral injection of lipopolysaccharide.
Anti-inflammatory strategies have attracted much interest for their potential to prevent further deterioration of Parkinson's disease. Recent experimental and clinical evidence indicate that statins - extensively used in medical practice as effective lipid-lowering agents - have also anti-inflammatory effects. In this study, we investigated the influence of simvastatin on the degenerative process of the dopaminergic neurons of the rat following intranigral injection of lipopolysaccharide (LPS), a potent inductor of inflammation that we have previously used as an animal model of Parkinson's disease. We evaluated TH positive neurons, astroglial, and microglial populations and found that simvastatin prevented the inflammatory processes, as the induction of interleukin-1beta, tumor necrosis factor-alpha, and iNOS and the consequent dopaminergic degeneration induced by LPS. Moreover, simvastatin produced the activation of the neurotrophic factor BDNF, along with the prevention of the oxidative damage to proteins. Moreover, it also prevents the main changes produced by LPS on different mitogen-activated protein kinases, featured as increases of P-c-Jun N-terminal protein kinase, P-extracellular signal-regulated kinase, p-38, and P-glycogen synthase kinase and the decrease of the promotion of cell survival signals such as cAMP response element-binding protein and Akt. Our results suggest that statins could delay the progression of dopaminergic degeneration in disorders involving inflammatory processes.
Hernández-Romero
María del Carmen
MC
Departamento de Bioquímica, Bromatología, Toxicología y Medicina Legal, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
Argüelles
Sandro
S
Villarán
Ruth F
RF
de Pablos
Rocío M
RM
Delgado-Cortés
María José
MJ
Santiago
Marti
M
Herrera
Antonio J
AJ
Cano
Josefina
J
Machado
Alberto
A
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
C026915:6-iodo-5-hydroxy-eicosatrienoic acid, delta-lactone; D000924:Anticholesteremic Agents; D001095:Arachidonic Acids; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin; D052247:Nitric Oxide Synthase Type II; D004298:Dopamine