Elucidating the time-dependent changes in the urinary metabolome under doxorubicin-induced nephrotoxicity

Li, Aiping; Zhang, Wang-Ning; Zhang, Lichao; Li, Ke; Du, Guanhua; Qin, Xuemei

doi:10.1016/j.toxlet.2019.11.020

Cited by 14 publications

(14 citation statements)

References 42 publications

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Section: Introductionmentioning

confidence: 99%

“…There are precedents for metabolic modeling of single-organ or complex multiorgan damage and partial recovery in experimental toxicology studies where the onset, progression, and recovery or nonrecovery from toxicity can be followed using biofluid metabolic models . Multiple studies using exemplar toxins that damage different organ systems in experimental animals at various times post dosing have been documented, − and some studies have shown sequential organ toxicity or recovery trajectories. , In such situations, functional biochemical recovery may occur at different rates and vary between individuals . We hypothesize that because SARS-CoV-2 infections frequently result in multiorgan involvement the functional recovery of patients might show similar complex temporal patterns and variations in biochemical normalization through time and that study of these processes can provide an objective functional classification of recovery.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

et al. 2021

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We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID-19 patients and the possible biochemical sequelae of “Post-Acute COVID-19 Syndrome”, colloquially known as long-COVID. Blood samples were taken from patients ca. 3 months after acute COVID-19 infection with further assessment of symptoms at 6 months. Some 57% of the patients had one or more persistent symptoms including respiratory-related symptoms like cough, dyspnea, and rhinorrhea or other nonrespiratory symptoms including chronic fatigue, anosmia, myalgia, or joint pain. Plasma samples were quantitatively analyzed for lipoproteins, glycoproteins, amino acids, biogenic amines, and tryptophan pathway intermediates using Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Metabolic data for the follow-up patients ( n = 27) were compared with controls ( n = 41) and hospitalized severe acute respiratory syndrome SARS-CoV-2 positive patients ( n = 18, with multiple time-points). Univariate and multivariate statistics revealed variable patterns of functional recovery with many patients exhibiting residual COVID-19 biomarker signatures. Several parameters were persistently perturbed, e.g., elevated taurine ( p = 3.6 × 10 –3 versus controls) and reduced glutamine/glutamate ratio ( p = 6.95 × 10 –8 versus controls), indicative of possible liver and muscle damage and a high energy demand linked to more generalized tissue repair or immune function. Some parameters showed near-complete normalization, e.g., the plasma apolipoprotein B100/A1 ratio was similar to that of healthy controls but significantly lower ( p = 4.2 × 10 –3 ) than post-acute COVID-19 patients, reflecting partial reversion of the metabolic phenotype (phenoreversion) toward the healthy metabolic state. Plasma neopterin was normalized in all follow-up patients, indicative of a reduction in the adaptive immune activity that has been previously detected in active SARS-CoV-2 infection. Other systemic inflammatory biomarkers such as GlycA and the kynurenine/tryptophan ratio remained elevated in some, but not all, patients. Correlation analysis, principal component analysis (PCA), and orthogonal-partial least-squares discriminant analysis (O-PLS-DA) showed that the follow-up patients were, as a group, metabolically distinct from controls and partially comapped with the acute-phase patients. Significant systematic metabolic differences between asymptomatic and symptomatic follow-up patients were also observed for multiple metabolites. The overall metabolic variance of the symptomatic patients was significantly greater than that of nonsymptomatic patients for multiple parameters (χ 2 p = 0.014). Thus, asymptomatic follow-up patients including those with post-acute COVID-19 Syndrome displayed a ...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

et al. 2021

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“…A better way would be to take blood not only terminally but also at different time points after adriamycin injection for both groups to define progressive markers. Recently, urinary metabolomics has been conducted to elucidate time-dependent changes in doxorubicin-induced nephropathy rat model in our study . Urine was selected in that study because it is (1) preferably easily accessible and noninvasive, (2) capable of analyzing metabolites at different points in the same animal, and (3) reflects kidney damage to some extent .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, urinary metabolomics has been conducted to elucidate time-dependent changes in doxorubicin-induced nephropathy rat model in our study. 28 Urine was selected in that study because it is (1) preferably easily accessible and noninvasive, (2) capable of analyzing metabolites at different points in the same animal, and (3) reflects kidney damage to some extent. 28 However, the number of rats needed for blood collection from the aorta abdominal at different time points is required relatively more, or they may be under stress due to blood-collecting from the fundus venous plexus.…”

Section: ■ Discussionmentioning

confidence: 99%

Evaluation of Injury Degree of Adriamycin-Induced Nephropathy in Rats Based on Serum Metabolomics Combined with Proline Marker

Yang

Zhang

et al. 2019

J. Proteome Res.

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Nephrotic syndrome (NS) is one of the leading causes of end-stage renal failure. Unfortunately, reliable surrogate markers for early diagnosing and monitoring the entire progression of NS are as yet absent. A method using UPLC-Q exactive HR-MS was established for the serum metabolomic study of adriamycin-induced nephropathy in rats. Two rat nephropathy models induced by adriamycin were adopted to reflect different degrees of renal damage of early and advanced stages. Then two MPC5 cell models were used to verify the role of proline in the progression of kidney injury. The results showed that seven metabolites such as 14S-HDHA, DPA, and DHA were associated with early renal injury, while 12 metabolites such as tryptophan, linoleyl carnitine, and LysoPC (18:3) reflected the advanced renal disease. At the same time, metabolites including LPE (22:6), LysoPC (22:5), and proline that changed during the whole process of NS were defined as progressive markers. Pathway analysis results showed that fatty acid metabolism, glycerophospholipid metabolism, and amino acids metabolism participated in the occurrence and development of NS. In addition, the change trend of intracellular proline content was consistent with that in serum, and the results were further supported by the detection of the crucial gene PYCRL. This study provides an important basis for searching for diagnostic markers of NS and also provides a methodological reference for early diagnosing and monitoring the pathogenesis of other progressive diseases.

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“…Kidney injury: this is another COVID-19 related serious complication as reviewed in [295]. Certain chemotherapeutic regimens make cancer patients more susceptible to nephrotoxicity [296]. TQ shows protective effects in the kidneys through ameliorating oxidative stress and reversing the nephrotoxic effects of various drugs and infections [24,25,226,233,234], as summarized in Table 4.…”

Section: The Significance Of Thymoquinone In Other Pathological Processes In Covid-cancer Patientsmentioning

confidence: 99%

Thymoquinone: A Tie-Breaker in SARS-CoV2-Infected Cancer Patients?

Elgohary

Elkhodiry

Amin

et al. 2021

Cells

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Since the beginning of the SARS-CoV-2(severe acute respiratory syndrome-coronavirus-2) pandemic, arace to develop a vaccine has been initiated, considering the massive and rather significant economic and healthcare hits that this virus has caused. The pathophysiology occurring following COVID-19(coronavirus disease-2019) infection has givenhints regarding the supportive and symptomatic treatments to establish for patients, as no specific anti-SARS-CoV-2 is available yet. Patient symptoms vary greatly and range from mild symptoms to severe fatal complications. Supportive treatments include antipyretics, antiviral therapies, different combinations of broad-spectrum antibiotics, hydroxychloroquine and plasma transfusion. Unfortunately, cancer patients are at higher risk of viral infection and more likely to develop serious complications due to their immunocompromised state, the fact that they are already administering multiple medications, as well as combined comorbidity compared to the general population. It may seem impossible to find a drug that possesses both potent antiviral and anticancer effects specifically against COVID-19 infection and its complications and the existing malignancy, respectively. Thymoquinone (TQ) is the most pharmacologically active ingredient in Nigella sativa seeds (black seeds); it is reported to have anticancer, anti-inflammatory and antioxidant effects in various settings. In this review, we will discuss the multiple effects of TQ specifically against COVID-19, its beneficial effects against COVID-19 pathophysiology and multiple-organ complications, its use as an adjuvant for supportive COVID-19 therapy and cancer therapy, and finally, its anticancer effects.

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Elucidating the time-dependent changes in the urinary metabolome under doxorubicin-induced nephrotoxicity

Cited by 14 publications

References 42 publications

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

Evaluation of Injury Degree of Adriamycin-Induced Nephropathy in Rats Based on Serum Metabolomics Combined with Proline Marker

Thymoquinone: A Tie-Breaker in SARS-CoV2-Infected Cancer Patients?

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