Conclusions
Combining Mel and Zn supplements with PMA defends against AlCl3-induced AD by modulating GSK-3β-Wnt/β-catenin signaling and palliates the associated hepatorenal dysfunction.
Methods
Seven groups of rats each received: saline (control group), AlCl3 (70 mg/kg, i.p.), PMA, either alone or with a combination of Mel (10 mg/kg, p.o) and/or Zn (16 mg/kg, p.o). Neurological deterioration was assessed after 5 weeks using behavioral tests, histopathological examination, and measurements of acetylcholinesterase (ACHE), brain monoamines, oxidative stress, and inflammatory markers, Amyloid precursor protein (APP), amyloid-β (Aβ), tau levels, and brain derived neurotrophic factor (BDNF). Moreover, the GSK-3β-Wnt/β-catenin signaling pathway was assessed. Additionally, oxidative stress and inflammatory markers were determined in liver and kidney tissues with concurrent evaluation of hepatic and renal functions.
Results
The histopathological examination revealed a cerebral cortex and hippocampus deterioration in the AD group with a decline in spatial learning and memory, besides a significant increase in AD markers in the brain and disturbance in GSK-3β-Wnt/β-catenin signaling. The AD group showed hepatorenal injuries supported by elevated oxidative stress and inflammatory markers. However, adding Mel and Zn to PMA significantly attenuated the neurodegeneration and enhanced hepatic and renal functions by ameliorating oxidant and inflammatory markers. Conclusions: Combining Mel and Zn supplements with PMA defends against AlCl3-induced AD by modulating GSK-3β-Wnt/β-catenin signaling and palliates the associated hepatorenal dysfunction.