Cardiac effects of MDMA on the metabolic profile determined with <sup>1</sup>H‐magnetic resonance spectroscopy in the rat

Perrine, Shane A.; Michaels, Mark S.; Ghoddoussi, Farhad; Hyde, Elisabeth; Tancer, Manuel E.; Galloway, Matthew P.

doi:10.1002/nbm.1352

Cited by 38 publications

(25 citation statements)

References 43 publications

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“…Interestingly we did detect a higher level of succinate in the cachectic tumors. Since succinate is produced in the tricarboxylic acid cycle (TCA) cycle from α-ketoglutarate (28), increased flux through the TCA cycle may explain a higher uptake of glucose without an increase of lactate.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Signatures Imaged in Cancer-Induced Cachexia

et al. 2011

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Cancer-induced cachexia is a complex and poorly understood life-threatening syndrome that is characterized by progressive weight loss due to metabolic alterations, depletion of lipid stores and severe loss of skeletal muscle protein. Gaining the ability to non-invasively image the presence or onset of cachexia is important to better treat this condition, to improve the design and optimization of therapeutic strategies, and to detect the responses to such treatments. In this study, we used noninvasive magnetic resonance spectroscopic imaging (MRSI) and [18F] fluorodeoxyglucose (18FDG) positron emission tomography (PET) to identify metabolic signatures typical of cachectic tumors, using this information to determine the types and extents of metabolic changes induced by the onset of cachexia in normal tissues. Cachexia was confirmed by weight loss as well as analyses of muscle tissue and serum. In vivo, cachexia-inducing MAC16 tumors were characterized by higher total choline (tCho) and higher 18FDG uptake compared to histologically similar non-cachectic MAC13 tumors. A profound depletion of the lipid signal was observed in normal tissue of MAC16 tumor bearing mice but not within the tumor tissue itself. High-resolution 1H MR spectroscopy (MRS) confirmed the high tCho level observed in cachectic tumors that occurred due to an increase of free choline and phosphocholine (PC). Higher succinate and lower creatine levels were also detected in cachectic tumors. Taken together, these findings enhance our understanding of cancer’s effect on host organs and tissues as well as promote the development of noninvasive biomarkers for the presence of cachexia and identification of new therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Metabolic Signatures Imaged in Cancer-Induced Cachexia

et al. 2011

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“…The effects of 3,4-methylenedioxymethamphetamine (commonly known as ecstasy) on cardiac metabolism in rats were monitored using in vivo 1 H-NMR spectroscopy. 63 The drug produced a number of metabolic changes in the heart, including an increase in the pool size of carnitine and a decrease in choline compared with wild-type rats. Doxorubicin cardiotoxicity has been monitored using a similar approach.…”

Section: Reviewsmentioning

confidence: 99%

Metabolomics as a tool for cardiac research

et al. 2011

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Metabolomics represents a paradigm shift in metabolic research, away from approaches that focus on a limited number of enzymatic reactions or single pathways, to approaches that attempt to capture the complexity of metabolic networks. Additionally, the high-throughput nature of metabolomics makes it ideal to perform biomarker screens for diseases or follow drug efficacy. In this Review, we explore the role of metabolomics in gaining mechanistic insight into cardiac disease processes, and in the search for novel biomarkers. High-resolution NMR spectroscopy and mass spectrometry are both highly discriminatory for a range of pathological processes affecting the heart, including cardiac ischemia, myocardial infarction, and heart failure. We also discuss the position of metabolomics in the range of functional-genomic approaches, being complementary to proteomic and transcriptomic studies, and having subdivisions such as lipidomics (the study of intact lipid species). In addition to techniques that monitor changes in the total sizes of pools of metabolites in the heart and biofluids, the role of stable-isotope methods for monitoring fluxes through pathways is examined. The use of these novel functional-genomic tools to study metabolism provides a unique insight into cardiac disease progression.

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“…HR-MAS 1 H-MRS, originally developed for analysis of solid state materials, provides a highly resolved chemical shift spectrum amenable to quantitation. As such, it is of substantial utility for assessing metabolic profiles in intact tissue specimens [23][24][25]. Neurochemical concentrations derived from 1 H-MRS of intact tissue are a unique measure (no chemical derivatization, tissue disruption, or solvent extraction) that can be readily compared to information derived from clinical 1 H-MRS.…”

Section: Introductionmentioning

confidence: 99%