Metabolomics in vitro in kidney cells – A tool for investigation of the nephrotoxicity

Birk, Barbara; Sperber, Saskia; Huener, Hans-Albrecht; Verlohner, Andreas; Walk, T.; Haake, Volker; Kamp, Hennicke; Ravenzwaay, B. van

doi:10.1016/j.toxlet.2017.07.389

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“…Metabonomics analysis of small biological molecules, using high‐sensitivity techniques, such as liquid chromatography/mass spectroscopy (LC/MS), combined with statistical analysis, identify differential metabolites between various treatments and can recognize the targets and mechanisms of toxins and potential interventions (Birk et al, 2017; Griffin, 2020; Uehara et al, 2014). Metabonomics has been widely used in disease diagnosis, pharmaceutical research and development, environmental science, and nutritional food science as well as toxicology (Lee & Banerjee, 2020; Xiao et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Analysis of cantharidin‐induced kidney injury and the protective mechanism of resveratrol in mice determined by liquid chromatography/mass spectrometry‐based metabonomics

Xiao,

Liu,

Zhang

et al. 2024

J of Applied Toxicology

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Cantharidin (CTD) is the main active component in the traditional Chinese medicine Mylabris and an effective anti‐tumor agent. However, it is relatively toxic and exhibits nephrotoxicity, which limits its clinical use. However, its toxic mechanism is not clear. The toxic effects of CTD exposure on the kidney and the protective effect of resveratrol (RES) were studied in a mouse model, by determination of serum biochemical and renal antioxidant indicators, histopathological and ultrastructural observation, and metabonomics. After CTD exposure, serum uric acid, creatinine, and tissue oxidative stress indicators increased, and the renal glomerular and tubular epithelial cells showed clear pathological damage. Ultrastructure observation revealed marked mitochondrial swelling, endoplasmic reticulum dilation, and the presence of autophagy lysosomes in glomerular epithelial cells. RES ameliorated the renal injury induced by CTD. Metabonomics analysis indicated that CTD can induce apoptosis and oxidative damage in kidney cells, mainly by disrupting sphingolipid and glutathione metabolism, increasing sphingosine and sphingomyelin levels, and decreasing glutathione levels. RES counteracts these effects by regulating renal cell proliferation, the inflammatory response, oxidative stress, and apoptosis, by improving the levels of phosphatidylcholine (PC), LysoPC, and lysophosphatidyl glycerol in the glycerophospholipid metabolism pathway, thereby reducing CTD‐induced nephrotoxicity. The mechanisms of CTD‐induced renal injury and the protective effect of RES were revealed by metabonomics, providing a basis for evaluating clinical treatment regimens to reduce CTD‐induced nephrotoxicity.

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