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

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

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1 Department of Human Genetics, Emory University School of Medicine , Atlanta, Georgia .



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.


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.


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.

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