A close association between brain metal dishomeostasis and the onset and/or progression of Alzheimer's disease (AD) has been clearly established in a number of studies, although the underlying biochemical mechanisms remain obscure. This observation renders chelation therapy an attractive pharmacological option for the treatment of this disease. However, a number of requirements must be fulfilled in order to adapt chelation therapy to AD so that the term "metal targeted strategies" seems now more appropriate. Indeed, brain metal redistribution rather than brain metal scavenging and removal is the major goal of this type of intervention. The most recent developments in metal targeted strategies for AD will be discussed using, as useful examples, clioquinol, curcumin, and epigallocatechin, and the future perspectives will also be outlined.
A total of 225 male broiler chicks (Cobb strain) of day-old age were procured for the study. The chicks were randomly divided into 15 groups consisting of 15 chicks in each group. Group 1 was maintained as basal diet control and group 2 on chlorpyrifos (CPS) at 100 ppm in feed throughout 6 wk as iron toxic control without any treatment. Groups 3-15 were maintained on CPS at 100 ppm in feed for the 4 wk (28 days) of study and thereafter administered with different herbs and their combinations for remaining 2 wk. The blood samples were drawn from wing vein on 28th day and 42nd day from the birds in each group for the estimation of lipid and protein profiles. The birds were sacrificed at the end of 6th week and liver tissues were collected for histological examination. The concentrations of total cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, total protein, albumin and globulins and the A/G ratio were increased significantly (P<;0.05) in toxic groups (2–15), while high density lipoprotein (HDL) cholesterol was significantly (P<;0.05) decreased at the end of 4th week. However, following supplementation of herbs and herbal combinations, the values of lipid and protein profile in groups 3–15 revived toward normal at the end of 6th week. Histopathology of liver in CPS toxic control (group 2) revealed areas of degeneration, while groups 3–15 that were treated with herbs and their combinations exhibited these changes in a milder form, indicating regenerative alterations. The study revealed that chorpyrifos-induced changes in lipid and protein profile were improved by supplementation of certain herbs.
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