Prevention of neurotoxicity and cognitive impairment induced by zinc nanoparticles by oral administration of saffron extract

J Anim Physiol Anim Nutr (Berl). 2023 Nov;107(6):1473-1494. doi: 10.1111/jpn.13848. Epub 2023 May 29.

Abstract

The accumulation of relatively higher dose of zinc oxide nanoparticles in brain was reported to produce neurotoxicity. Indeed, nanoparticles have a high ability to penetrate biological membranes and be uptaken by cells, which may cause cell disorders and physiological dysfunctions. The aim of the current study was to evaluate, whether oral administration of saffron extract, in rats, can protect from neurotoxicity and behavioural disturbances induced by chronic administration of ZnO-NPs. Daily oral administration of ZnO-NPs was performed for 21 consecutive days to induce oxidative stress-like situation. Then after the saffron extract was concomitantly administrated in several rat groups to overcome the nanotoxicological effect induced by ZnO-NPs. In the frontal cortex, the hippocampus and the cerebellum, ZnO-NPs induced a H2 O2 -oxydative stress-like effect reflected in reduced enzymatic activities of catalase, superoxide dismutase and glutathione S-transferase, and decreased acetylcholinesterase activity. In addition, increased levels of proinflammatory interleukins IL-6 and IL-1-⍺ occurred in the hippocampus, reveal the existence of brain inflammation. The concomitant administration of saffron extract to animals exposed to ZnO-NPs prevented the enhanced anxiety-related to the behaviour in the elevated plus-maze test, the open field test and preserved spatial learning abilities in the Morris water maze. Moreover, animals exposed to ZnO-NPs and saffron showed abnormal activity of several antioxidant enzymes as well as acetylcholinesterase activity, an effect that may underly the preserved anxiety-like behaviour and spatial learning abilities observed in these animals. Saffron extract has a potential beneficial therapeutic effect: antioxidant, anti-inflammatory and neuroprotective agent.

Keywords: anxiety; inflammatory cytokines; oxidative stress; saffron extract; spatial learning and memory; zinc oxide nanoparticles.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Acetylcholinesterase / pharmacology
  • Administration, Oral
  • Animals
  • Antioxidants / metabolism
  • Cognitive Dysfunction*
  • Crocus* / metabolism
  • Metal Nanoparticles* / toxicity
  • Oxidative Stress
  • Rats
  • Zinc / pharmacology
  • Zinc Oxide* / toxicity

Substances

  • Antioxidants
  • Zinc
  • Acetylcholinesterase
  • Zinc Oxide