Role of fibrillar Abeta25-35 in the inflammation induced rat model with respect to oxidative vulnerability.
The major pathological ramification of Alzheimer's disease (AD) is accumulation of beta-Amyloid (Abeta) peptides in the brain. An emerging therapeutic approach for AD is elimination of excessive Ass peptides and preventing its re-accumulation. Immunization is the most effective strategy in removing preexisting cerebral Abetas and improving the cognitive capacity as shown in transgenic mice model of AD. However, active immunization is associated with adverse effect such as encephalitis with perivascular inflammation and hemorrhage. Details about the mechanistic aspects of propagation of these toxic effects are matter of intense enquiry as this knowledge is essential for the understanding of the AD pathophysiology. The present work aimed to study the oxidative vulnerability in the plasma, liver and brain of the inflammation-induced rats subjected to Ass immunization. Induction of inflammation was performed by subcutaneous injection of 0.5?ml of 2% silver nitrate. Our present result shows that the proinflammatory cytokines such as IL1alpha and TNFalpha are increased significantly in the inflammation-induced, Abeta1-42, Abeta25-35 treated groups and inflammation with Abeta25-35 treated group when compared to control, complete Freund's adjuvant and Abeta35-25 treated groups. These increased proinflammatory cytokines concurrently releases significant amount of free radicals in the astrocytes of respected groups. The present result shows that nitric oxide (NO) level was significantly higher (P<0.001) in plasma, liver and brain of the rat subjected to inflammation, Abeta1-42, Abeta25-35 and inflammation with Abeta25-35 injected groups when compared to control. The increased level of lipid peroxides (LPO) (P<0.001) and decreased antioxidant status (P<0.05) were observed in the plasma, liver and brain of inflammation-induced group when compared to control. Our result shows that significant oxidative vulnerability was observed in the inflammation with Ass treated rats when compared to other groups. Based on our results, we suggest that immunization of AD patients with Ass should be done with caution as the increase in Ass could trigger the brain inflammation in uncontrollable level.
Masilamoni
J G
JG
Bio-Organic and Neurochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai, 600 020, India.
Jesudason
E P
EP
Jesudoss
K S
KS
Murali
J
J
Paul
S F D
SF
Jayakumar
R
R
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016229:Amyloid beta-Peptides; D007375:Interleukin-1; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C074636:amyloid beta-protein (25-35); D009569:Nitric Oxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001205:Ascorbic Acid