Noha F Abdelkader1, Aya M Abd El-Latif2, Mahmoud M Khattab2. 1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt. Electronic address: noha.fawzy@pharma.cu.edu.eg. 2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt.
Abstract
AIMS: The higher incidence rate of Alzheimer's disease (AD) among women has led to explorations on the association between estrogen deficiency and AD. Also, usage of antihypertensive drugs has been suggested to reduce the incidence of AD in elderly hypertensive patients. Thus, this study aimed to investigate the effects of telmisartan and/or 17β-estradiol on a cognitively impaired ovariectomized rat model of AD. MAIN METHODS: 75 female Wistar rats were randomly allocated into five groups. One group was sham operated and the other four groups were subjected to ovariectomy, received D-galactose and either untreated or treated with telmisartan and/or 17β-estradiol for 6 weeks. KEY FINDINGS: Ovariectomized rats showed cognitive impairment in Morris water maze and novel object recognition tests, increasing inflammatory biomarkers (tumor necrosis factor-α, and interleukin-1β), increasing AD biomarkers (amyloid beta1-42, and acetylcholine esterase), and over activation of classical arm of renin angiotensin system (RAS) (ACE1/Ang2/AT1) in hippocampi. Also, hippocampi histopathological examination revealed amyloid beta deposition. Whereas, administration of telmisartan and/or 17β-estradiol improved animals' behavior, alleviated histopathological alterations and reduced the level of inflammatory and AD biomarkers, modulated RAS activity favoring the novel neuroprotective arm (ACE2/Ang(1-7)/MasR). SIGNIFICANCE: Our findings suggest that combined administration of both drugs has synergetic neuroprotective effects; supporting their potential application in AD treatment.
AIMS: The higher incidence rate of Alzheimer's disease (AD) among women has led to explorations on the association between estrogen deficiency and AD. Also, usage of antihypertensive drugs has been suggested to reduce the incidence of AD in elderly hypertensivepatients. Thus, this study aimed to investigate the effects of telmisartan and/or 17β-estradiol on a cognitively impaired ovariectomized rat model of AD. MAIN METHODS: 75 female Wistar rats were randomly allocated into five groups. One group was sham operated and the other four groups were subjected to ovariectomy, received D-galactose and either untreated or treated with telmisartan and/or 17β-estradiol for 6 weeks. KEY FINDINGS: Ovariectomized rats showed cognitive impairment in Morris water maze and novel object recognition tests, increasing inflammatory biomarkers (tumor necrosis factor-α, and interleukin-1β), increasing AD biomarkers (amyloid beta1-42, and acetylcholine esterase), and over activation of classical arm of renin angiotensin system (RAS) (ACE1/Ang2/AT1) in hippocampi. Also, hippocampi histopathological examination revealed amyloid beta deposition. Whereas, administration of telmisartan and/or 17β-estradiol improved animals' behavior, alleviated histopathological alterations and reduced the level of inflammatory and AD biomarkers, modulated RAS activity favoring the novel neuroprotective arm (ACE2/Ang(1-7)/MasR). SIGNIFICANCE: Our findings suggest that combined administration of both drugs has synergetic neuroprotective effects; supporting their potential application in AD treatment.
Authors: Hajira Dambha-Miller; Ali Albasri; Sam Hodgson; Christopher R Wilcox; Shareen Khan; Nazrul Islam; Paul Little; Simon J Griffin Journal: BMJ Open Date: 2020-09-14 Impact factor: 2.692
Authors: Yoelvis Garcia-Mesa; He N Xu; Patricia Vance; Analise L Gruenewald; Rolando Garza; Cecily Midkiff; Xavier Alvarez-Hernandez; David J Irwin; Alexander J Gill; Dennis L Kolson Journal: Antioxidants (Basel) Date: 2021-03-09