Psychiatry Research EG

Introduction The major cause of dementia, a major public health problem, is Alzheimer’s disease (AD). A reliable method for the diagnosis and follow up of AD is needed together with a specific biological marker. Galantamine (Gal), an acetylcholinesterase inhibitor for AD therapy, has several reported side effects. Aim of the Work One approach to reduce dosing amounts, frequency of administration, and adverse side effects while maintaining the drug efficiency is the development of drug delivery systems using nanoparticles. Material and Methods Presently, Galantamine with either cerium/calcium hydroxyapatite (Ce/Ca-HAp) or carboxymethyl chitosan/ceria/calcium hydroxyapatite (CMCS/Ce/Ca-HAp) was intraperitoneally injected at a dose of 2.5 mg/kg body weight for 2 and 4 weeks. A total of 86 female adult albino Wistar rats (189–200 g weight) were used. AD was induced in ovariectomized rats with aluminum chloride oral treatment at doses of 17 mg/kg body weight daily for 2 months. The rats were divided into six groups: group 1, which included normal control rats; group 2, which included rats treated with Gal injected intraperitoneally at a dose of 2.5 mg/kg body weight; group 3, which included rats with AD; group 4, which included AD-induced rats treated intraperitoneally with Gal; group 5, which included AD-induced rats treated with Gal coated with Ce/Ca-HAp; group 6, which included AD-induced rats treated with Gal coated with CMCS/Ce/Ca-HAp for 2 and 4 weeks. Results In the current study, AD-induced histological alterations manifested as amyloid plaque formation of different sizes, congestion with perivascular edema, degenerated neurons with diffused gliosis, loss of pyramidal cells, separation of cortical tissue, and formation of fibrous glial scar. Several tests may be cumulatively used for early detection as decreased acetylcholine, B-cell lymphoma 2, tissue thromboplastin, GSH, superoxide dismutase, CAT, and cytochrome P450 and increased amyloid β, Chol, brain-type fatty acid binding protein, nitric oxide, MDA, and GSSH. Treatment with Gal coated with Ce/Ca-HAp imposed a highly significant improvement to near-to-normal levels in both histological and biochemical parameters. Gal coated with CMCS/Ce/Ca-HAp failed to encounter obvious ameliorations. Conclusion In conclusion, brain markers (acetylcholine, B-cell lymphoma 2, amyloid β, tissue thromboplastin, Chol, brain-type fatty acid binding protein, nitric oxide, and MDA) together with brain antioxidants (GSH, superoxide dismutase, CAT, and cytochrome P450) may be used in progressive laboratory testing method besides well-known imaging techniques. Gal therapy may impose limited improvements; thus, drug delivery systems using Gal coated with Ce/Ca-HAp may aid in minimizing dosing amounts, frequency of administration, and adverse side effects of drug while increasing its therapeutic efficacy. Keywords: Alzheimer`s, disease, carboxymethyl chitosan/ceria/hydroxyapatite composite, ceria-doped calcium hydroxyapatite, galantamine, histology and biochemistry, rat