Resveratrol prolongs lifespan and improves 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced oxidative damage and behavioural deficits in Drosophila melanogaster

Biochem Biophys Res Commun. 2018 Sep 5;503(2):1042-1048. doi: 10.1016/j.bbrc.2018.06.114. Epub 2018 Jun 27.

Abstract

1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) is a neurotoxin that causes Parkinson's disease in animals via mechanisms linked with oxidative stress and inflammation. Resveratrol is a natural polyphenol and a phytoalexin with antioxidative and antiinflammatory properties. Here, we investigated the rescue role of resveratrol on MPTP-triggered toxicity in Drosophila melanogaster for the first time. D. melanogaster (Harwich strain, 1-to 3- days old) were first orally exposed to resveratrol (0, 7.5, 15, 30, 60 and 120 mg/kg diet) and MPTP (0, 250, 500, 1000, 2000, and 3000 μM) for longevity and 7 days survival assays respectively. Consequently, we selected resveratrol (30 and 60 mg/kg diet) to evaluate its rescue role on MPTP (250 and 500 μM)-induced toxicity in D. melanogaster after 3 days of oral treatment. Specifically, we evaluated markers of neurotoxicity (acetylcholinesterase and negative geotaxis), inflammation (nitric oxide), oxidative stress-antioxidant status (hydrogen peroxide, total thiol, catalase and glutathione-S-transferase), cell viability and fecundity. The data showed that resveratrol increased lifespan of D. melanogaster in a dose-dependent manner up to 60 mg/kg diet. Further, resveratrol restored MPTP-induced inhibition of catalase, glutathione-S-transferase and acetylcholinesterase activities in D. melanogaster. Moreover, resveratrol ameliorated MPTP-triggered cell death, histological alterations, behavioural deficits and accumulation of nitric oxide and hydrogen peroxide levels in flies (p < 0.05). Conclusively, the lifespan extension effects of resveratrol and its rescue role on MPTP- mediated toxicity in the flies may be due to its antioxidant and anti-inflammatory properties.

Keywords: 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine; Oxidative stress; Parkinson's disease; Resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / adverse effects*
  • Acetylcholinesterase / metabolism
  • Animals
  • Antioxidants / pharmacology*
  • Behavior, Animal / drug effects
  • Catalase / metabolism
  • Cell Survival / drug effects
  • Drosophila melanogaster / drug effects*
  • Drosophila melanogaster / physiology
  • Glutathione Transferase / metabolism
  • Hydrogen Peroxide / metabolism
  • Longevity / drug effects
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects*
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / metabolism
  • Resveratrol / pharmacology*

Substances

  • Antioxidants
  • Nitric Oxide
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Hydrogen Peroxide
  • Catalase
  • Glutathione Transferase
  • Acetylcholinesterase
  • Resveratrol