Effect of excessive cholesterol and lipopolysaccharide on cerebellar neuronal cells in in vitro and protective role of anti-inflammatory drugs.
The present work was carried out to elucidate the role of NSAIDs, PPARg agonist and HMG CoA inhibitor on cholesterol and lipopolysaccharide (LPS) induced neurodegeneration. The cerebellar, neuronal cells were exposed to cholesterol (10 and 50 microg/ml), LPS (1 ng/ml) or both. Neuroprotective effect of ibuprofen, rofecoxib, simvastatin and pioglitazone was assessed by measuring the neuronal loss, MTT dye assay, nitric oxide, LDH and lipid peroxide measurement. The results indicated that incubation of cholesterol and LPS showed less synaptic connections, neurite outgrowth and cell shrinkage as compared to normal cerebellar cells. Significantly decreased survival cells count along with increased LDH, lipid peroxide and nitrite levels were observed in the cells that confirmed neurodegeneration with cholesterol and LPS challenge. In comparison to individual toxins (LPS or cholesterol), combination of LPS and cholesterol produced more deleterious effect indicated synergistic effect of toxins. Interestingly, in comparison to LPS, cholesterol produced significantly low level of nitrites, LDH and lipid peroxides which indicated excessive cholesterol might not influence radical generation directly and might be a secondary effect. Among the drugs studied, NSAIDs showed better effect indicated inflammatory mediator response played vital role in cholesterol and LPS induced neurodegeneration. Simvastatin demonstrated moderate neuroprotective effect. It could be concluded that excessive cholesterol might produce cell death and led to release of nitrites and other cytokines. NSAIDs had better neuroprotective activity than simvastatin that produced moderate effect.
Ramanathan
M
M
Neuropharmacology Laboratory, Department of Pharmacology, JSS College of Pharmacy, Rocklands, Ootacamund 643 001, India. muthiah.in@gmail.com
Deshmuk
D
D
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D002784:Cholesterol