Analysis of spatiotemporal metabolomic dynamics for sensitively monitoring biological alterations in cisplatin-induced acute kidney injury

Irie, Miho; Hayakawa, Eisuke; Fujimura, Yoshinori; Honda, Youhei; Setoyama, Daiki; Wariishi, Hiroyuki; Hyodo, Fuminori; Miura, Daisuke

doi:10.1016/j.bbrc.2018.01.012

Cited by 11 publications

(20 citation statements)

References 27 publications

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“…The impact of cDDP in cell division was observed for the first time in 1965 (in E. coli ) and the compound was approved as an antineoplastic agent in 1978 [2]. CDDP is presently used, often in combination with other drugs, for treatment of many different types of cancer, e.g., head and neck, lung, testicular, ovarian, and bladder cancer [1,3]. However, its clinical use is limited to some extent due to frequently acquired drug resistance and severe cytotoxic effects such as nephrotoxicity, hepatotoxicity, cardiotoxicity, neurotoxicity, and bone marrow toxicity [3].…”

Section: Introductionmentioning

confidence: 99%

“…CDDP is presently used, often in combination with other drugs, for treatment of many different types of cancer, e.g., head and neck, lung, testicular, ovarian, and bladder cancer [1,3]. However, its clinical use is limited to some extent due to frequently acquired drug resistance and severe cytotoxic effects such as nephrotoxicity, hepatotoxicity, cardiotoxicity, neurotoxicity, and bone marrow toxicity [3]. Attempts to overcome these drawbacks have been made through the development of several other Pt (or other metal)-based drugs, such as carboplatin (a Pt complex with bidentate cyclobutane dicarboxylic acid replacing the chloride ions), which represents one of the most successful [1].…”

Section: Introductionmentioning

confidence: 99%

“…Although biofluids metabolic profiles carry valuable information on the systemic metabolic response to cDDP, and may be an important source of non-invasive early markers of drug toxicity, tissue metabolic analyses (including but not restricted to kidney) may provide important information on local deviant metabolism and interorgan metabolic interplays. To our knowledge, only cisplatin-exposed kidney tissue has been studied through metabolomics, notably using MS-based untargeted metabolomics [3,42,43]. The first studies addressed Sprague-Dawley (SD) rats, with an early report monitoring both urine and kidney tissue after 1, 5, and 28 days post cDDP injection (0.5 mg/kg) [42].…”

Section: Introductionmentioning

confidence: 99%

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Multi-Organ NMR Metabolomics to Assess In Vivo Overall Metabolic Impact of Cisplatin in Mice

et al. 2019

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This work describes, to our knowledge, the first NMR metabolomics analysis of mice kidney, liver, and breast tissue in response to cisplatin exposure, in search of early metabolic signatures of cisplatin biotoxicity. Balb/c mice were exposed to a single 3.5 mg/kg dose of cisplatin and then euthanized; organs (kidney, liver, breast tissue) were collected at 1, 12, and 48 h. Polar tissue extracts were analyzed by NMR spectroscopy, and the resulting spectra were studied by multivariate and univariate analyses. The results enabled the identification of the most significant deviant metabolite levels at each time point, and for each tissue type, and showed that the largest metabolic impact occurs for kidney, as early as 1 h post-injection. Kidney tissue showed a marked depletion in several amino acids, comprised in an overall 13-metabolites signature. The highest number of changes in all tissues was noted at 12 h, although many of those recovered to control levels at 48 h, with the exception of some persistently deviant tissue-specific metabolites, thus enabling the identification of relatively longer-term effects of cDDP. This work reports, for the first time, early (1–48 h) concomitant effects of cDDP in kidney, liver, and breast tissue metabolism, thus contributing to the understanding of multi-organ cDDP biotoxicity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multi-Organ NMR Metabolomics to Assess In Vivo Overall Metabolic Impact of Cisplatin in Mice

et al. 2019

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“…Broadly speaking, MS approaches have been explored as a source of metabolism-based biomarkers of renal disease in several contexts 5,24,25 . Urine has been the most common biospecimen type analyzed, and a number of metabolites and panels of metabolites that correlate with specific diseases have been identified 5,24–29 . Although some metabolites have been observed across studies, most metabolic changes appear to be poorly reproducible between independent patient sets, different diseases, and different animal model systems.…”

Section: Discussionmentioning

confidence: 99%

Early detection of unilateral ureteral obstruction by desorption electrospray ionization mass spectrometry

Banerjee

Wong

Yan

et al. 2019

Sci Rep

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Desorption electrospray ionization mass spectrometry (DESI-MS) is an emerging analytical tool for rapid in situ assessment of metabolomic profiles on tissue sections without tissue pretreatment or labeling. We applied DESI-MS to identify candidate metabolic biomarkers associated with kidney injury at the early stage. DESI-MS was performed on sections of kidneys from 80 mice over a time course following unilateral ureteral obstruction (UUO) and compared to sham controls. A predictive model of renal damage was constructed using the LASSO (least absolute shrinkage and selection operator) method. Levels of lipid and small metabolites were significantly altered and glycerophospholipids comprised a significant fraction of altered species. These changes correlate with altered expression of lipid metabolic genes, with most genes showing decreased expression. However, rapid upregulation of PG(22:6/22:6) level appeared to be a hitherto unknown feature of the metabolic shift observed in UUO. Using LASSO and SAM (significance analysis of microarrays), we identified a set of well-measured metabolites that accurately predicted UUO-induced renal damage that was detectable by 12 h after UUO, prior to apparent histological changes. Thus, DESI-MS could serve as a useful adjunct to histology in identifying renal damage and demonstrates early and broad changes in membrane associated lipids.

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“…The concentration of serum UA directly reflects the severity of hyperuricemia (Aksenov, Peck, Eriksson, & Stanski, 2018), and the level of XO is another important indicator directly associated with hyperuricemia (Park et al, 2018). The symptoms of hyperuricemia can be relieved when the UA level is decreased (Filler, Lopes, & Awuku, 2015;Irie et al, 2018;Pulzer et al, 2001;Zhu et al, 2018). In the mice with hyperuricemia, AM strongly suppressed the serum levels of UA and XO and reduced the concentrations of BUN and Cr.…”

Section: Discussionmentioning

confidence: 99%

Aronia melanocarpa ameliorates gout and hyperuricemia in animal models

Wang

Han

et al. 2018

Food and Agricultural Immunology

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Aronia melanocarpa fruit (AM) strongly suppressed ankle swelling in rats with acute gout and reduced the levels of uric acid and xanthine oxidase (XO) in mice with hyperuricemia. AM reduced the inflammatory cell count and increased the ankle joint space, and suppressed the levels of interleukin (IL)-1β, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor-α in the serum of the rats with acute gout. In the mice with hyperuricemia, AM significantly reduced the serum levels of uric acid, blood urea nitrogen, and creatinine. 8-day administration of AM resulted in enhancements in the levels of glutathione peroxidase, superoxide dismutase and catalase and a reduction in the level of malondialdehyde in the serum of mice. All data suggested that the potential therapeutic effects of AM on gout are probably due to the regulation of pro-and anti-inflammatory cytokines and the suppression of XO activity via modulation of the oxidative stress status.

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Analysis of spatiotemporal metabolomic dynamics for sensitively monitoring biological alterations in cisplatin-induced acute kidney injury

Cited by 11 publications

References 27 publications

Multi-Organ NMR Metabolomics to Assess In Vivo Overall Metabolic Impact of Cisplatin in Mice

Multi-Organ NMR Metabolomics to Assess In Vivo Overall Metabolic Impact of Cisplatin in Mice

Early detection of unilateral ureteral obstruction by desorption electrospray ionization mass spectrometry

Aronia melanocarpa ameliorates gout and hyperuricemia in animal models

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