Abstract
Metabolomic profiling using hydrophilic interaction chromatography in combination with Fourier transform mass spectrometry was used to study the effects of the xanthine oxidase inhibitor allopurinol on wild type Drosophila melanogaster. Allopurinol treatment phenocopied the rosy mutation causing an elevation in the levels of xanthine and hypoxanthine and a fall in the levels of uric acid and allantoin. However, in addition there were some unexpected metabolic changes after treatment. Ascorbic acid levels were undetectable, glutathione levels fell and glutathione disulphide levels rose, methionine S-oxide levels rose and riboflavin levels fell. The origin of this oxidative stress was not immediately apparent; however, there was a strong suggestion that it might be related to a fall in NADPH levels linked to a reduction in glucose-6-phosphate dehydrogenase activity, resulting in reduced levels of some metabolites in the pentose phosphate pathway. In addition to producing oxidative stress there were marked effects on tryptophan metabolism with most of the metabolites in the kynurenine pathway being lowered by allopurinol treatment. The effects on the kynurenine pathway could be related to the established use of allopurinol in treating schizophrenia.
| Language | English |
|---|---|
| Pages | 542-548 |
| Number of pages | 7 |
| Journal | Metabolomics |
| Volume | 7 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Dec 2011 |
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Keywords
- drosophila
- metabolomics
- rosy
- Fourier transform mass spectrometry
- allopurinol
- oxidative stress
- kynurenine pathway
- uric acid
- stress
- double blind
- urate
- schizophrenia
- antioxidant
- stroke
Cite this
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Metabolomic profiling of the effects of allopurinol on Drosophila melanogaster. / Al Bratty, Mohammed; Hobani, Yahya; Dow, Julian A. T.; Watson, David G.; Watson, David.
In: Metabolomics, Vol. 7, No. 4, 12.2011, p. 542-548.Research output: Contribution to journal › Article
TY - JOUR
T1 - Metabolomic profiling of the effects of allopurinol on Drosophila melanogaster
AU - Al Bratty, Mohammed
AU - Hobani, Yahya
AU - Dow, Julian A. T.
AU - Watson, David G.
AU - Watson, David
PY - 2011/12
Y1 - 2011/12
N2 - Metabolomic profiling using hydrophilic interaction chromatography in combination with Fourier transform mass spectrometry was used to study the effects of the xanthine oxidase inhibitor allopurinol on wild type Drosophila melanogaster. Allopurinol treatment phenocopied the rosy mutation causing an elevation in the levels of xanthine and hypoxanthine and a fall in the levels of uric acid and allantoin. However, in addition there were some unexpected metabolic changes after treatment. Ascorbic acid levels were undetectable, glutathione levels fell and glutathione disulphide levels rose, methionine S-oxide levels rose and riboflavin levels fell. The origin of this oxidative stress was not immediately apparent; however, there was a strong suggestion that it might be related to a fall in NADPH levels linked to a reduction in glucose-6-phosphate dehydrogenase activity, resulting in reduced levels of some metabolites in the pentose phosphate pathway. In addition to producing oxidative stress there were marked effects on tryptophan metabolism with most of the metabolites in the kynurenine pathway being lowered by allopurinol treatment. The effects on the kynurenine pathway could be related to the established use of allopurinol in treating schizophrenia.
AB - Metabolomic profiling using hydrophilic interaction chromatography in combination with Fourier transform mass spectrometry was used to study the effects of the xanthine oxidase inhibitor allopurinol on wild type Drosophila melanogaster. Allopurinol treatment phenocopied the rosy mutation causing an elevation in the levels of xanthine and hypoxanthine and a fall in the levels of uric acid and allantoin. However, in addition there were some unexpected metabolic changes after treatment. Ascorbic acid levels were undetectable, glutathione levels fell and glutathione disulphide levels rose, methionine S-oxide levels rose and riboflavin levels fell. The origin of this oxidative stress was not immediately apparent; however, there was a strong suggestion that it might be related to a fall in NADPH levels linked to a reduction in glucose-6-phosphate dehydrogenase activity, resulting in reduced levels of some metabolites in the pentose phosphate pathway. In addition to producing oxidative stress there were marked effects on tryptophan metabolism with most of the metabolites in the kynurenine pathway being lowered by allopurinol treatment. The effects on the kynurenine pathway could be related to the established use of allopurinol in treating schizophrenia.
KW - drosophila
KW - metabolomics
KW - rosy
KW - Fourier transform mass spectrometry
KW - allopurinol
KW - oxidative stress
KW - kynurenine pathway
KW - uric acid
KW - stress
KW - double blind
KW - urate
KW - schizophrenia
KW - antioxidant
KW - stroke
UR - http://www.scopus.com/inward/record.url?scp=80054016623&partnerID=8YFLogxK
U2 - 10.1007/s11306-011-0275-6
DO - 10.1007/s11306-011-0275-6
M3 - Article
VL - 7
SP - 542
EP - 548
JO - Metabolomics
T2 - Metabolomics
JF - Metabolomics
SN - 1573-3882
IS - 4
ER -