Biological interactions and attenuation of MPTP-induced toxicity in Drosophila melanogaster by Trans-astaxanthin

Neurosci Res. 2023 Nov:196:52-58. doi: 10.1016/j.neures.2023.06.005. Epub 2023 Jun 15.

Abstract

Trans-astaxanthin (TA) is a carotenoid with amphipathic chemical structure found in yeast, and aquatic organisms. It is known to possess both antioxidative and anti-inflammatory properties. This study was carried out to investigate the ameliorative action of TA on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in Drosophila melanogaster (Fruit fly). The flies were orally treated with TA (2.5 mg/10 g diet) and/or MPTP (500 µM) for 5 days. Thereafter, we evaluated selected biomarkers of locomotor deficits (acetylcholinesterase (AChE) and negative geotaxis), oxidative stress (hydrogen peroxide (H2O2), protein carbonyls (PC)), antioxidants (total thiols (T-SH), non-protein thiols, glutathione-S-transferase (GST) and catalase), and inflammation (nitric oxide (nitrite/nitrate) in the flies. Furthermore, we investigated molecular docking analysis of TA against Kelch-like ECH-associated protein 1 (Keap1)) of Homo sapiens and D. melanogaster. The results indicated that TA increased MPTP-induced decreased activities of AChE, GST, and catalase, as well as levels of non-protein thiols and T-SH compared with MPTP-treated flies (p < 0.05). Furthermore, TA attenuated inflammation, and improved locomotor deficit in the flies. The molecular docking data showed that TA had docking scores for binding both the Human and Drosophila Keap1, nearly closer to or higher than the standard inhibitor. The attenuating effects of TA against MPTP-induced toxicity could arise from its antioxidative and anti-inflammatory properties as well as its chemical structure.

Keywords: Molecular docking; Oxidative stress; Parkinsonism; Trans-astaxanthin.

MeSH terms

  • Acetylcholinesterase* / metabolism
  • Acetylcholinesterase* / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Catalase / metabolism
  • Drosophila melanogaster*
  • Humans
  • Hydrogen Peroxide / metabolism
  • Hydrogen Peroxide / pharmacology
  • Inflammation
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Molecular Docking Simulation
  • NF-E2-Related Factor 2 / metabolism
  • NF-E2-Related Factor 2 / pharmacology
  • Oxidative Stress
  • Sulfhydryl Compounds / metabolism
  • Sulfhydryl Compounds / pharmacology

Substances

  • Catalase
  • Kelch-Like ECH-Associated Protein 1
  • astaxanthine
  • Acetylcholinesterase
  • Hydrogen Peroxide
  • NF-E2-Related Factor 2
  • Antioxidants
  • Anti-Inflammatory Agents
  • Sulfhydryl Compounds