New bithiophene derivative attenuated Alzheimer's disease induced by aluminum in a rat model via antioxidant activity and restoration of neuronal and synaptic transmission
AbdEl-Raouf, Kholoud; Farrag, Hussein S.H.; Rashed, Rashed; Ismail, Mohamed A; El-Ganzuri, Monir A.; El-Sayed, Wael;
Abstract
Background: One of the hypotheses that leads to an increased incidence of Alzheimer's disease (AD) is the accumulation of aluminum in the brain's frontal cortex. The present study aimed to evaluate the therapeutic role of a novel bithiophene derivative at two doses against AlCl3-induced AD in a rat model. Methodology: Adult male rats were divided into six groups, 18 rats each. Group 1: naïve animals, group 2: animals received a daily oral administration of bithiophene dissolved in DMSO (1 mg/kg) for 30 days every other day, groups 3–6: animals received a daily oral administration of AlCl3 (100 mg/kg/day) for 45 consecutive days. Groups 4 and 5 received an oral administration of low or high dose of the bithiophene (0.5 or 1 mg/kg, respectively). Group 6; Animals were treated with a daily oral dose of memantine (20 mg/kg) for 30 consecutive days. Main findings: Al disturbed the antioxidant milieu, elevated the lipid peroxidation, and depleted the antioxidants. It also disturbed the synaptic neurotransmission by elevating the activities of acetylcholine esterase and monoamine oxidase resulting in the depletion of dopamine and serotonin and accumulation of glutamate and norepinephrine. Al also deteriorated the expression of genes involved in apoptosis and the production of amyloid-β plaques as well as phosphorylation of tau. The new bithiophene at the low dose reversed most of the previous deleterious effects of aluminum in the cerebral cortex and was in many instances superior to the reference drug; memantine. Conclusion: Taking together, the bithiophene modulated the AD etiology through antioxidant activity, prevention of neuronal and synaptic loss, and probably mitigating the formation of amyloid-β plaques and phosphorylation of tau.
Other data
Title | New bithiophene derivative attenuated Alzheimer's disease induced by aluminum in a rat model via antioxidant activity and restoration of neuronal and synaptic transmission | Authors | AbdEl-Raouf, Kholoud; Farrag, Hussein S.H.; Rashed, Rashed; Ismail, Mohamed A ; El-Ganzuri, Monir A.; El-Sayed, Wael | Keywords | AChE;Antioxidants;GSK3-β;MAO;Neurotransmitters | Issue Date | 1-Mar-2024 | Journal | Journal of Trace Elements in Medicine and Biology | Volume | 82 | ISSN | 0946672X | DOI | 10.1016/j.jtemb.2023.127352 | PubMed ID | 38070385 | Scopus ID | 2-s2.0-85179493157 |
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