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

Molecules. 2021 Nov 8;26(21):6752. doi: 10.3390/molecules26216752.

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.

Keywords: Alzheimer’s; BDNF; GSK-3β; Triticum aestivum; hepatotoxicity; nephrotoxicity; tau protein; β-amyloid; β–catenin.

MeSH terms

  • Aluminum Chloride / antagonists & inhibitors
  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Animals
  • Fluoxetine / pharmacology*
  • Kidney / drug effects*
  • Kidney / pathology
  • Liver / drug effects*
  • Liver / pathology
  • Male
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Wistar
  • Triticum / chemistry*

Substances

  • Neuroprotective Agents
  • Fluoxetine
  • Aluminum Chloride