Manganese-based superoxide dismutase mimics modify both acute and long-term outcome severity in a Drosophila melanogaster model of classic galactosemia

Antioxid Redox Signal. 2014 May 20;20(15):2361-71. doi: 10.1089/ars.2012.5122. Epub 2013 Jul 20.


Aims: The goal of this study was to use two manganese (Mn)-based superoxide dismutase (SOD) mimics to test the hypothesis that reactive oxygen species contribute to both acute and long-term outcomes in a galactose-1P uridylyltransferase (GALT)-null Drosophila melanogaster model of classic galactosemia.

Results: We tested the impact of each of two Mn porphyrin SOD mimics, MnTnBuOE-2-PyP(5+), and MnTE-2-PyP(5+), (i) on survival of GALT-null Drosophila larvae reared in the presence versus absence of dietary galactose and (ii) on the severity of a long-term movement defect in GALT-null adult flies. Both SOD mimics conferred a significant survival benefit to GALT-null larvae exposed to galactose but not to controls or to GALT-null larvae reared in the absence of galactose. One mimic, MnTE-2-PyP(5+), also largely rescued a galactose-independent long-term movement defect otherwise seen in adult GALT-null flies. The survival benefit of both SOD mimics occurred despite continued accumulation of elevated galactose-1P in the treated animals, and studies of thiolated proteins demonstrated that in both the presence and absence of dietary galactose MnTE-2-PyP(5+) largely prevented the elevated protein oxidative damage otherwise seen in GALT-null animals relative to controls.

Innovation and conclusions: Our results confirm oxidative stress as a mediator of acute galactose sensitivity in GALT-null Drosophila larvae and demonstrate for the first time that oxidative stress may also contribute to galactose-independent adult outcomes in GALT deficiency. Finally, our results demonstrate for the first time that both MnTnBuOE-2-PyP(5+) and MnTE-2-PyP(5+) are bioavailable and effective when administered through an oral route in a D. melanogaster model of classic galactosemia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cysteine / blood
  • Cysteine / metabolism
  • Disease Models, Animal
  • Drosophila melanogaster
  • Galactose / metabolism
  • Galactosemias / drug therapy
  • Galactosemias / genetics
  • Galactosemias / metabolism*
  • Galactosemias / mortality
  • Glutathione / blood
  • Glutathione / metabolism
  • Male
  • Metabolic Networks and Pathways
  • Metalloporphyrins / pharmacokinetics
  • Metalloporphyrins / pharmacology
  • Molecular Mimicry*
  • Oxidation-Reduction / drug effects
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / chemistry
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase / pharmacology


  • Metalloporphyrins
  • Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin
  • Reactive Oxygen Species
  • Superoxide Dismutase
  • Glutathione
  • Cysteine
  • Galactose