Ni and Al mixture amplifies cerebellar oxido-inflammatory responses, down regulates AChE and BDNF/NGF levels in motor impairment in male albino rats

J Trace Elem Med Biol. 2023 Dec:80:127318. doi: 10.1016/j.jtemb.2023.127318. Epub 2023 Oct 11.

Abstract

Background: Aluminum and nickel are potent neurotoxicants to which humans are constantly exposed. Previous studies have demonstrated that these two metals can affect the motor system, but their effects on the cerebellum, a central nervous system region with the highest number of neurons, have remained largely unexplored. Therefore, we conducted a study to investigate the adverse effects of Al, Ni, and Al+Ni in vivo.

Methods: In our study, seven male Sprague Dawley rats per group were orally exposed to deionized water, 0.2 mg/kg of Ni, 1 mg/kg of Al, and 0.2 mg/kg of Ni + 1 mg/kg of Al (as a binary heavy metals mixture; HMM), respectively.

Results: Ni, Al, and HMM exposed rats accumulated higher levels of Al and Ni compared to controls, and HMM treated animals had higher levels of Ca and Fe in the cerebellum (p < 0.05). Malondialdehyde (MDA) levels were significantly (p < 0.05) higher in the HMM, Ni, and Al treated groups compared to the control group that received deionized water. Superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx) activities were significantly (p < 0.05) reduced in the HMM, Ni, and Al treated groups compared to the control group that received deionized water. Ni, Al, and HMM significantly (p < 0.05) shortened the length of time of the grip in comparison to the control. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels were significantly decreased in the nickel, Al, and heavy metal mixture groups compared with the control group. Moreover, there was a significant decrease in the activity of acetylcholinesterase (AChE) and a increase in cyclooxygenase-2 (COX-2) activity in the Ni, Al, and HMM treated groups compared to the control group.

Conclusion: HMM exposed animals had significantly poorer performance in the Rotarod test (p < 0.05) than controls. Al and Ni induced impairment of cerebellar function at various levels.

Keywords: Acetylcholine; Heavy metal mixture; Neurotoxicity; Neurotrophic factor; Oxido-inflammatory.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Antioxidants / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Catalase / metabolism
  • Cerebellum / metabolism
  • Glutathione / metabolism
  • Humans
  • Male
  • Metals, Heavy* / pharmacology
  • Motor Disorders*
  • Nerve Growth Factor / metabolism
  • Nerve Growth Factor / pharmacology
  • Nickel / pharmacology
  • Oxidative Stress
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism
  • Water / pharmacology

Substances

  • Acetylcholinesterase
  • Nickel
  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factor
  • Metals, Heavy
  • Antioxidants
  • Catalase
  • Glutathione
  • Superoxide Dismutase
  • Water