Metabolomics as a tool to evaluate the toxicity of formulations containing amphotericin B, an antileishmanial drug

Santos, Délia Chaves Moreira dos; Lima, Marta Lopes; Toledo, Juliano Simões de; Fernandes, Paula Ávila; Aguiar, Marta M. G.; López‐Gonzálvez, Ángeles; Ferreira, Lucas Antônio Miranda; Fernandes, Ana Paula; Barbas, Coral

doi:10.1039/c6tx00253f

Cited by 6 publications

(5 citation statements)

References 59 publications

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“…Therefore, it can be postulated that butanol and butanal metabolites, especially 3-hydroxybutyric acid, play an important role in the parasite metabolism and the leaf extract of X. stumarium inhibits the growth of Leishmania promastigotes by disrupting this metabolic pathway and inhibiting ATP supply. Our results are supported by previous finding (31).…”

Section: Discussionsupporting

confidence: 94%

“…No significant study was observed on the role and probable importance of butanol and butanal in the maintenance and survival of promastigotes. The previous metabolomics-based investigation, confirmed 3-hydroxybutyric alteration in mice treated with new amphotericin B drug compound (31). This drug compound had less toxic effects on patients with Leishmaniasis (32).…”

Section: Discussionmentioning

confidence: 59%

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Metabolomics Based Study of the Antileishmanial Activity of Xanthium strumarium Leaf Extract on Promastigotes Phases of Leishmania major by Proton NMR Spectroscopy

Ahmadi

Akbari

Alikhani

et al. 2019

IJPA

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Background: Xanthium strumarium L. is extensively used as a traditional herb to treat many diseases and is also known as a source of phytochemicals. It has been used traditionally to treat trypanosomiasis, malaria fever, eczema, cancer, ulcer, fever, herpes headache, and skin lesion such as leishmaniasis. In this preliminary study, nuclear magnetic resonance (NMR)-metabolomics approaches was used to evaluate the inhibitory effects and metabolic alterations caused by leaf extract of X. strumarium on the stationary phases of promastigotes in Leishmania major. Methods: The promastigotes were cultured in Biochemistry Laboratory at Pasteur Institute of Iran in 2017, stationary phases were obtained from 5 to 6 day-old cultures and treated with different concentrations of the plant’s extract. Antileishmanial activity was assayed by MTT method and cell metabolites were extracted. 1H NMR spectroscopy was applied, and outliers were separated using multivariate statistical analysis. Results: The most affected metabolic pathways in the experimental groups were limited to amino sugar and nucleotide sugar metabolism, cyanoamino acid metabolism, starch and sucrose metabolism, butanoate metabolism, and galactose metabolism. Conclusion: The ethanolic leaf extract of X. strumarium is a potent growth inhibitor of Leishmania major and can affect vital metabolic pathways of Leishmania promastigotes. The assay provided new perspectives on the development of novel treatment strategies for leishmanial activity derived from natural products.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 59%

Metabolomics Based Study of the Antileishmanial Activity of Xanthium strumarium Leaf Extract on Promastigotes Phases of Leishmania major by Proton NMR Spectroscopy

Ahmadi

Akbari

Alikhani

et al. 2019

IJPA

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“… 8 In human patients, metabolic profiles correlate with the presence and prognosis of neoplastic and cardiovascular diseases, 9 , 10 and can be further used to predict adverse effects and facilitate early discontinuation of ineffective or harmful treatments. 11 Advances in metabolic profiling are thereby paving the way for individualized medicine and therapeutic drug targeting. 12 …”

Section: Introductionmentioning

confidence: 99%

Seasonal variation in serum metabolites of northern European dogs

Walker

Ottka

Lohi

et al. 2021

Veterinary Internal Medicne

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Background Metabolic profiling identifies seasonal variance of serum metabolites in humans. Despite the presence of seasonal disease patterns, no studies have assessed whether serum metabolites vary seasonally in dogs. Hypothesis There is seasonal variation in the serum metabolite profiles of healthy dogs. Animals Eighteen healthy, client‐owned dogs. Methods A prospective cohort study. Serum metabolomic profiles were assessed monthly in 18 healthy dogs over a 12‐month period. Metabolic profiling was conducted using a canine‐specific proton nuclear magnetic resonance spectroscopy platform, and the effects of seasonality were studied for 98 metabolites using a cosinor model. Seasonal component was calculated, which describes the seasonal variation of each metabolite. Results We found no evidence of seasonal variation in 93 of 98 metabolites. Six metabolites had statistically significant seasonal variance, including cholesterol (mean 249 mg/dL [6.47 mmol/L] with a seasonal component amplitude of 9 mg/dL [0.23 mmol/L]; 95% confidence interval [CI] 6‐13 mg/dL [0.14‐0.33 mmol/L], P < .008), with a peak concentration of 264 mg/dL (6.83 mmol/L) in June and trough concentration of 236 mg/dL (6.12 mmol/L) in December. In contrast, there was a significantly lower concentration of lactate (mean 20 mg/dL [2.27 mmol/L] with a seasonal component amplitude of 4 mg/dL [0.42 mmol/L]; 95% CI 2‐6 mg/dL [0.22‐0.62 mmol/L], P < .001) during the summer months compared to the winter months, with a peak concentration of 26 mg/dL (2.9 mmol/L) in February and trough concentration of 14 mg/dL (1.57 mmol/L) in July. Conclusions and Clinical Importance We found no clear evidence that seasonal reference ranges need to be established for serum metabolites of dogs.

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“…Renal and hepatic function deterioration is a serious side effect limiting the use of AmB, even in commercial formulations, 62,71 its consequences being well documented in the literature. 18,71,79–81 For instance, hemorrhage, coagulative necrotic areas and the presence of pale hepatocytes as well as single-cell necrosis of hepatocytes with neutrophil aggregation have been observed in the livers of mice treated with Fungizone®. 71,81 Free-AmB seems to promote mild necrotic hepatocytes with moderate infiltration of the portal tract by inflammatory cells in mouse livers.…”

Section: Resultsmentioning

confidence: 99%

“…71,81 Free-AmB seems to promote mild necrotic hepatocytes with moderate infiltration of the portal tract by inflammatory cells in mouse livers. 80 In the case of the nephrotoxicity, AmB can promote renal vasoconstriction (which reduces the renal blood flow and glomerular filtration rate 79 ) and decrease the viability of renal tubular epithelial cells through alterations in cell membrane permeability, via pore formation, 82,83 promoting tubular necrosis. 18 Also, degenerative changes of renal glomerular tuft associated with abundant inflammatory cell infiltrates and intercellular edema has been observed.…”

Section: Resultsmentioning

confidence: 99%

Hyaluronic acid–amphotericin B nanocomplexes: a promising anti-leishmanial drug delivery system

et al. 2022

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Metabolomics as a tool to evaluate the toxicity of formulations containing amphotericin B, an antileishmanial drug

Cited by 6 publications

References 59 publications

Metabolomics Based Study of the Antileishmanial Activity of Xanthium strumarium Leaf Extract on Promastigotes Phases of Leishmania major by Proton NMR Spectroscopy

Metabolomics Based Study of the Antileishmanial Activity of Xanthium strumarium Leaf Extract on Promastigotes Phases of Leishmania major by Proton NMR Spectroscopy

Seasonal variation in serum metabolites of northern European dogs

Hyaluronic acid–amphotericin B nanocomplexes: a promising anti-leishmanial drug delivery system

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