Vanadium improves brain acetylcholinesterase activity on early stage alloxan-diabetic rats.
The present study is designed to screen the possible effects of sodium orthovanadate therapy on the kinetic parameters of brain membrane-bound and soluble acetylcholinesterase (AChE) forms in alloxan-induced diabetic rats. The diabetic rats were treated with 300 mg/kg sodium orthovanadate orally for 45 days. While diabetes significantly decreased the brain specific activity (V(max)) of AChE soluble form by 42%, it caused a fivefold increase of the K(m) of the membrane-bound form. Furthermore, the activity of brain glutathione-S-transferase (GST) was significantly decreased and this was associated with a remarkable increase in brain lipid peroxidative parameter, thiobarbituric acid reactive substances (TBARS), as compared to sham control. The alterations of both AChE forms observed in diabetic state could be attributed to hyperglycemia and lipid peroxidation that triggered brain dysfunction by disturbing the neurotransmitter acetylcholine level. Administration of sodium orthovanadate reversed the diabetic conditions by lowering the blood glucose level and normalized the blood Hb(A1C) level. It also normalized the levels of brain AChE, GST and TBARS as compared to diabetic state and control. Therefore, vanadate administration could protect against direct action of lipid peroxidation on brain AChE and in this way, it might be useful in the prevention of cholinergic neural dysfunction, which is one of the major complications in diabetes.
Ghareeb
Doaa A
DA
Department of Biochemistry, Moharm Bak 00203, Faculty of Science, University of Alexandria, Alexandria, Egypt. hadiergad@yahoo.com
Hussen
Hend M
HM
D000110:Acetylcholinesterase / Q000187:drug effects* / Q000378:metabolism; D000496:Alloxan / Q000633:toxicity; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007527:Isoenzymes / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014638:Vanadates / Q000627:therapeutic use*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007527:Isoenzymes; D017392:Thiobarbituric Acid Reactive Substances; D014638:Vanadates; D000496:Alloxan; D005982:Glutathione Transferase; D000110:Acetylcholinesterase