Attenuation of Rotenone-Induced Mitochondrial Oxidative Damage and Neurotoxicty in Drosophila melanogaster Supplemented with Creatine

Creatine (Cr), an ergogenic nutritional supplement
is demonstrated to possess bioenergetic, antiexcitotoxic
and antioxidant properties. This study investigated
the neuroprotective effects of Cr against rotenone induced
oxidative stress, mortality and neurotoxicty in Drosophila
melanogaster. We found significant diminution in the
endogenous levels of oxidative markers in whole body
homogenates of flies exposed to Cr (2–10 mM). Cr supplementation
resulted in reduced mortality in flies
exposed to rotenone (500 lM) and better performance in
a negative geotaxis assay. Further Cr (10 mM) markedly
offset rotenone induced mitochondrial oxidative stress,
completely restored the GSH levels, nitric oxide levels,
activity of Mn-SOD and dopamine depletion. In an
oxidative stress bioassay, flies given Cr prophylaxis
exhibited marked resistance to paraquat exposure. These
data allow us to hypothesize that the neuroprotective
action of Cr in Drosophila may be related to its direct
antioxidant activity and ability to abrogate rotenone
induced mitochondrial oxidative stress.