Protection of mouse brain from aluminum-induced damage by caffeic acid.
The natural product caffeic acid is a specific inhibitor of 5-lipoxygenase (5-LOX); it also possesses antioxidant and antiinflammatory properties. The current study was designed to determine whether the neuroprotective properties of caffeic acid are due to inhibition of 5-LOX. Cerebral damage was induced in mice by intracerebroventricular microinjection of aluminum (5.0 microg aluminum in 2.0 microL, once a day, for 5 days). Caffeic acid was administered intragastrically at 30 min prior to aluminum and repeated daily for an additional 10 days. The brain injury was determined by observation of behavioral changes in mice, as well as by measuring biochemical and pathological changes in the cerebral tissue. The levels of 5-LOX proteins and 5-LOX mRNA expression were measured in brain tissue. Aluminum impaired learning and memory in mice produced neuronal death in hippocampi, elevated brain malondialdehyde levels, increased protein expression of amyloid precursor protein (APP), amyloid beta, and 5-LOX. It also increased 5-LOX mRNA expression and decreased choline acetyl transferase (ChAT) protein expression in the brain tissue of mice. Caffeic acid prevented brain damage as well as behavioral and biochemical changes caused by aluminum overload. The results of this study suggest that overexpression of 5-LOX accompanies the cerebral injury induced by aluminum overload in mice, and that selective inhibitors of 5-LOX may have potential value in the treatment of aluminum neurotoxicity and conceivably of diseases associated with neuronal injury.
Yang
Jun-Qing
JQ
Department of Pharmacology, Chongqing Medical University, Chongqing, PR China. cqjqyang2004@yahoo.com.cn
Zhou
Qi-Xin
QX
Liu
Bei-Zhong
BZ
He
Bai-Cheng
BC
D000535:Aluminum; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001930:Brain Injuries / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002109:Caffeic Acids / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013028:Space Perception / Q000187:drug effects
D000975:Antioxidants; D002109:Caffeic Acids; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D008315:Malondialdehyde; D000535:Aluminum; D001094:Arachidonate 5-Lipoxygenase; C040048:caffeic acid