Induction of cross-tolerance between protective effect of morphine and nicotine in 6-hydroxydopamine-induce neurotoxicity in SH-SY5Y human dopaminergic neuroblastoma cells

Int J Neurosci. 2019 Feb;129(2):129-138. doi: 10.1080/00207454.2018.1494169. Epub 2018 Sep 5.

Abstract

Purpose: Parkinson's disease is a progressive neurodegenerative disease characterized by progressive and selective death of dopaminergic neurons. It has been reported that nicotine and morphine have protective roles during neuronal damage in Parkinson's disease. In addition, the induction of cross-tolerance between their biological effects has been shown in numerous reports.

Methods: Here, we investigated the effects of nicotine and morphine on 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of Parkinson's disease. Cell damage was induced by 150 μM 6-OHDA and the cells viability was examined by MTT assay. Intracellular reactive oxygen species, calcium level, and mitochondrial membrane potential were determined by fluorescence spectrophotometer method. Biochemical markers of apoptosis were also evaluated by immunoblotting.

Result: The data showed that morphine and nicotine prevent 6-OHDA- induced cell damage and apoptosis. However, the protective effects of nicotine were not observed in chronic morphine-pretreated cells. Morphine had no protective effects in chronic nicotine-incubated cells.

Conclusion: A cross-tolerance between protective effects of morphine and nicotine was occurred in 6-OHDA-induced SH-SY5Y cell toxicity.

Keywords: 6-hydroxydopamine; Apoptosis; Morphine; Nicotine; Parkinson’s disease; SH-SY5Y cells.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA Fragmentation / drug effects
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / metabolism
  • Drug Tolerance*
  • Humans
  • Morphine / administration & dosage*
  • Neuroprotective Agents / administration & dosage*
  • Nicotine / administration & dosage*
  • Oxidopamine / toxicity
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism
  • Parkinsonian Disorders / chemically induced
  • Reactive Oxygen Species

Substances

  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Nicotine
  • Morphine
  • Oxidopamine