The mitochondrial uncoupler 2,4-dinitrophenol attenuates sodium nitroprusside-induced toxicity in Drosophila melanogaster: potential involvement of free radicals.
The toxicity of sodium nitroprusside (SNP) (an inducer of oxidative/nitrosative stress) and the attenuation of SNP effects by 2,4-dinitrophenol (DNP) (that induces mild uncoupling of respiration) were evaluated in the Drosophila melanogaster model system. Fly larvae were raised on food supplemented with 1.0 mM SNP, 0.5 or 1.25 mM DNP, or with mixtures 1.0 mM SNP plus 0.5 or 1.25 mM DNP. Food supplementation with SNP decreased larval viability and pupation height whereas supplementation with DNP substantially reversed these changes. Biochemical analyses of oxidative stress markers and activities of antioxidant and associated enzymes were carried out on 2-day-old flies emerged from control larvae and larvae fed on food supplemented with SNP, DNP, or SNP/DNP mixtures. Larval exposure to SNP lowered activities of aconitase, while the presence of DNP reduced the negative impact of SNP by raising aconitase activity back to near control levels. Larval treatment with SNP also elevated the contents of carbonyl protein, uric acid and low molecular mass thiols and produced higher activities of superoxide dismutase, glutathione S-transferase, glucose-6-phosphate dehydrogenase and thioredoxin reductase in adult flies. However, the presence of DNP in the food mixtures prevented SNP-induced changes in thioredoxin reductase and glucose-6-phosphate dehydrogenase activities, as well as uric acid and low-molecular-mass thiol content. The potential mechanisms by which DNP exerts protective effects against SNP toxicity are discussed.
Department of Biochemistry and Biotechnology, Precarpathian National University named after Vassyl Stefanyk, 57 Shevchenko Str., Ivano-Frankivsk, 76025, Ukraine.
Oleksandr V
OV
Lozinsky
Oleh V
OV
Lushchak
Janet M
JM
Storey
Kenneth B
KB
Storey
Volodymyr I
VI
Lushchak
D019297:2,4-Dinitrophenol / Q000008:administration & dosage / Q000494:pharmacology*; D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000254:growth & development / Q000378:metabolism*; D004336:Drug Antagonism; D005609:Free Radicals / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology / Q000600:supply & distribution; D014527:Uric Acid / Q000378:metabolism
D029721:Drosophila Proteins; D005609:Free Radicals; D020030:Nitric Oxide Donors; D013438:Sulfhydryl Compounds; D014475:Uncoupling Agents; D009599:Nitroprusside; D014527:Uric Acid; D005954:Glucosephosphate Dehydrogenase; D013482:Superoxide Dismutase; D013880:Thioredoxin-Disulfide Reductase; D005982:Glutathione Transferase; D000154:Aconitate Hydratase; D019297:2,4-Dinitrophenol
2,4-Dinitrophenol; 2,4-dinitrophenol; 5,5′-dithio-bis (2-nitro) benzoic acid; DNP; DTNB; EDTA; G6PDH; GSH/GSSG; GST; ICDH; L-SH; NADP-dependent isocitrate dehydrogenase; NADP/NADPH; Oxidative/nitrosative stress; PC; PMSF; RNS; ROS; Reactive nitrogen species; Reactive oxygen species; SOD; Sodium nitroprusside; TrxR; ethylenediaminetetraacetate; glucose-6-phosphate dehydrogenase; glutathione-S-transferase; low molecular mass thiols; oxidized/reduced glutathione; oxidized/reduced nicotinamide adenine dinucleotide phosphate; phenylmethylsulfonyl fluoride; protein carbonyls; reactive nitrogen species; reactive oxygen species; superoxide dismutase; thioredoxin reductase