Abstract
AbstractAlzheimer’s disease (AD), the most common neurodegenerative disorder, is characterized by behavioral, cognitive, and progressive memory impairments. Extensive neuronal loss, extracellular accumulation of insoluble senile amyloid-β (Aβ) plaques, and intracellular neurofibrillary tangles (NFTs) are the major pathological features. The present study aimed to investigate the therapeutic effect of donepezil (DON) and pentoxifylline (PTX) in combination to combat the neurodegenerative disorders (experimental AD) induced by CuSO4 intake in experimental rats. Thirty adult male Wistar rats (140–160 g) were used in this study. AD was first induced in rats by CuSO4 supplement to drinking water (10 mg/L) for 14 weeks. The AD group received no further treatment. Oral treatment with DON (10 mg/kg/day), PTX (100 mg/kg/day), or DON + PTX for the other three groups was started from the 10th week of CuSO4 intake for 4 weeks. Cortex markers like acetylcholine (ACh), acetylcholinesterase (AChE), total antioxidant capacity (TAC), and malondialdehyde (MDA) and hippocampus markers like β-amyloid precursor protein cleaving enzyme 1 (BACE1), phosphorylated Tau (p-tau), Clusterin (CLU), tumor necrosis factor-α (TNF-α), caspase-9 (CAS-9), Bax, and Bcl-2 were measured. The histopathology studies were done by using hematoxylin and eosin and Congo red stains as well as immunohistochemistry for neurofilament. CuSO4 induced adverse histological and biochemical changes. The histological injury in the hippocampus was inhibited following the administration of the DON and PTX. The brain tissue levels of AChE, MDA, BACE1, p-tau, CLU, CAS-9, Bax, and TNF-α were significantly increased, while brain tissue levels of ACh, TAC, and Bcl-2 were significantly decreased in CuSO4-treated rats as compared with the untreated control group. The effects induced by either DON or PTX on most studied parameters were comparable. Combined treatment of DON and PTX induced remarkable results compared with their individual use. However, more clinical and preclinical studies are still required to further confirm and prove the long-term efficacy of such combination.
Publisher
Springer Science and Business Media LLC
Subject
Toxicology,General Neuroscience
Reference68 articles.
1. Akbari Z, Reisi P, Torkaman-Boutorabi A, Farahmandfar M (2020) Effect of pentoxifylline on apoptotic-related gene expression profile, learning and memory impairment induced by systemic lipopolysaccharide administration in the rat hippocampus. Int J Prev Med 11:151
2. Albersen M, Fandel TM, Zhang H, Banie L, Lin G, De Ridder D, Lin CS, Lue TF (2011) Pentoxifylline promotes recovery of erectile function in a rat model of postprostatectomy erectile dysfunction. Eur Urol 59:286–296
3. Ali AA, Abd El-Fattah AI, Abu-Elfotuh K, Elariny HA (2021) Natural antioxidants enhance the power of physical and mental activities versus risk factors inducing progression of Alzheimer’s disease in rats. Int Immunopharmacol 96:107729
4. Alzoubi KH, Khabour OF, Tashtoush NH, Al-Azzam SI, Mhaidat NM (2013) Evaluation of the effect of pentoxifylline on sleep-deprivation induced memory impairment. Hippocampus 23:812–819
5. Arowoogun J, Akanni OO, Adefisan AO, Owumi SE, Tijani AS, Adaramoye OA (2021) Rutin ameliorates copper sulfate-induced brain damage via antioxidative and anti-inflammatory activities in rats. J Biochem Mol Toxicol 35:e22623