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 microM) 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.
Hosamani
Ravikumar
R
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Council of Scientific and Industrial Research, Mysore, India.
Ramesh
Saraf R
SR
Muralidhara
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D003401:Creatine / Q000008:administration & dosage*; D019587:Dietary Supplements; D004298:Dopamine / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012402:Rotenone / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D015996:Survival Rate; D014475:Uncoupling Agents / Q000633:toxicity
D000975:Antioxidants; D015415:Biomarkers; D007306:Insecticides; D014475:Uncoupling Agents; D012402:Rotenone; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D003401:Creatine; D004298:Dopamine