The protective effects of chitosan and curcumin nanoparticles against the hydroxyapatite nanoparticles-induced neurotoxicity in rats

Sci Rep. 2024 Sep 9;14(1):21009. doi: 10.1038/s41598-024-70794-9.

Abstract

Hydroxyapatite nanoparticles (HANPs) have extensive applications in biomedicine and tissue engineering. However, little information is known about their toxicity. Here, we aim to investigate the possible neurotoxicity of HANPs and the possible protective role of chitosan nanoparticles (CNPs) and curcumin nanoparticles (CUNPs) against this toxicity. In our study, HANPs significantly reduced the levels of neurotransmitters, including acetylcholine (Ach), dopamine (DA), serotonin (SER), epinephrine (EPI), and norepinephrine (NOR). HANPs significantly suppressed cortical expression of the genes controlling mitochondrial biogenesis such as peroxisome proliferator activator receptor gamma coactivator 1α (PGC-1α) and mitochondrial transcription factor A (mTFA). Our findings revealed significant neuroinflammation associated with elevated apoptosis, lipid peroxidation, oxidative DNA damage and nitric oxide levels with significant decline in the antioxidant enzymes activities and glutathione (GSH) levels in HANPs-exposed rats. Meanwhile, co-supplementation of HANP-rats with CNPs and/or CUNPs significantly showed improvement in levels of neurotransmitters, mitochondrial biogenesis, oxidative stress, DNA damage, and neuroinflammation. The co-supplementation with both CNPs and CUNPs was more effective to ameliorate HANPs-induced neurotoxicity than each one alone. So, CNPs and CUNPs could be promising protective agents for prevention of HANPs-induced neurotoxicity.

Keywords: Chitosan nanoparticles (CNPs); Curcumin nanoparticles (CUNPs); Hydroxyapatite nanoparticles (HANPs); Mitochondrial biogenesis; Neuroinflammation; Oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Chitosan* / chemistry
  • Chitosan* / pharmacology
  • Curcumin* / pharmacology
  • DNA Damage / drug effects
  • Durapatite* / chemistry
  • Lipid Peroxidation / drug effects
  • Male
  • Nanoparticles* / chemistry
  • Neuroprotective Agents / pharmacology
  • Neurotoxicity Syndromes / drug therapy
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / prevention & control
  • Neurotransmitter Agents / metabolism
  • Oxidative Stress* / drug effects
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Rats

Substances

  • Curcumin
  • Chitosan
  • Durapatite
  • Neuroprotective Agents
  • Neurotransmitter Agents
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha