Attenuative Effects of Fluoxetine and Triticum aestivum against Aluminum-Induced Alzheimer’s Disease in Rats: The Possible Consequences on Hepatotoxicity and Nephrotoxicity

Abstract

Background: Alzheimer’s disease (AD) is a chronic neurological illness that causes considerable cognitive impairment. Hepatic and renal dysfunction may worsen AD by disrupting β-amyloid homeostasis at the periphery and by causing metabolic dysfunction. Wheatgrass (Triticum aestivum) has been shown to have antioxidant and anti-inflammatory properties. This work aims to study the effect of aluminum on neuronal cells, its consequences on the liver and kidneys, and the possible role of fluoxetine and wheatgrass juice in attenuating these pathological conditions. Method: Rats were divided into five groups. Control, AD (AlCl3), Fluoxetine (Fluoxetine and AlCl3), Wheatgrass (Wheatgrass and AlCl3), and combination group (fluoxetine, wheatgrass, and AlCl3). All groups were assigned daily to different treatments for five weeks. Conclusions: AlCl3 elevated liver and kidney enzymes, over-production of oxidative stress, and inflammatory markers. Besides, accumulation of tau protein and Aβ, the elevation of ACHE and GSK-3β, down-regulation of BDNF, and β–catenin expression in the brain. Histopathological examinations of the liver, kidney, and brain confirmed this toxicity, while treating AD groups with fluoxetine, wheatgrass, or a combination alleviates toxic insults. Conclusion: Fluoxetine and wheatgrass combination demonstrated a more significant neuroprotective impact in treating AD than fluoxetine alone and has protective effects on liver and kidney tissues.

Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways

“…Nuclear degeneration and pyknosis were found in the cerebral cortex, subiculum, and fascia dentata. These outcomes agree with earlier studies by Abu-Elfotuh et al and Hamdan et al [ 54 ]. The present study unveils the promising neuroprotective effects of cocoa-based nutraceuticals, either alone or in combination with other dietary supplements, in mitigating the underlying histopathological deterioration.…”

“…Like our results, cocoa exhibited anti-inflammatory activity by reducing inflammatory TNF-α in alcohol-induced liver toxicity models in rats [ 53 ]. In addition, it was reported previously that VIN and WG inhibited Aβ-induced toxicity by inhibiting TNF-α and IL-1β [ 54 ]. Prior research has revealed that EGCG can mitigate amyloid β-induced toxicity by modulating the activity of TNF-α [ 55 ].…”

Neuroprotective Role of Periplocin Against Aluminium Chloride-stimulated Alzheimer’s Disease in a Rat Model by Modulation of Oxidative Stress and Inflammation

“…37 The pathophysiology of Alzheimer's disease is strongly linked to an uncontrolled neuroinflammatory process, like the overexpression of inflammatory mediators like IL-1β, which in turn suppresses the formation of the brain-derived neurotrophic factors responsible for the conduct of physiological functions in the CNS. 38,39 Furthermore, patients with high levels of AlCl 3 demonstrated cognitive deterioration, which has been linked to impaired pro-inflammatory regulators including TNF-α. 31 Cardiac glycosides like periplocin may be beneficial in addressing inflammation at the brain's periphery, opening up new avenues for medication development for neuroinflammatory degeneration.…”

Misuse of Cardiac Lipid upon Exposure to Toxic Trace Elements—A Focused Review

“…The environmental contamination with TTEs is both natural and anthropogenic. It can affect almost all the organs, but mainly the heart, kidney, liver, lungs, and nervous system [ 6 , 7 , 8 ].…”