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

Abstract

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.

Integration of Non-targeted Proteomics Mass Spectrometry with Machine Learning for Screening Cooked Beef Adulterated Samples

“…PCA was applied to reveal the data structure. The characteristic ion peaks of the raw and heat-processed samples for differentiating the different meat species were screened by PLS-DA with the parameters of V + S -plots (VIP ≥ 1, | p (corr)| ≥ 0.5, and | p | ≥ 0.05). − By comparing the characteristic ion peaks of the raw and the corresponding heat-processed samples, the persistent ion peaks without complete degradation after the heat treatment (i.e., the overlapping characteristic ion peaks of the raw and the corresponding heat-processed samples) were regarded as heat-stable characteristic proteins. These heat-stable characteristic proteins of four meat species were further confirmed from their presence in the MALDI MS raw spectra with a sufficient signal-to-noise ratio (S/N > 3) and were then identified through the protein database UniProt ().…”

Differences in Multicomponent Pharmacokinetics, Tissue Distribution, and Excretion of Tripterygium Glycosides Tablets in Normal and Adriamycin–Induced Nephrotic Syndrome Rat Models and Correlations With Efficacy and Hepatotoxicity

“…For rats, the optimal intravenous dose of adriamycin used to induce NS ranges from 1.5 to 7.5 mg/kg ( Lee and Harris, 2011 ). The M1 rats were induced with a 4 mg/kg dose of adriamycin through tail vein injection on day 1 and an additional 2 mg/kg dose of adriamycin after 1 week ( Li et al, 2019 ; Li et al, 2020 ), while the M2 rats were induced with a single 7.5 mg/kg intravenously dose of adriamycin ( Guo et al, 2014 ; Ni et al, 2018 ). The Con rats were injected with an equal volume of sterile saline.…”

Doxorubicin-induced nephrotoxicity model in Wistar rats: Characterization of biochemical parameters, histological and immunohistochemical assessment

“…The DXR-induced experimental nephrotoxicity model in rodents is a classical pharmacological animal model that simulates the early pathophysiological characteristics of kidney damage (Li et al, 2019;He et al, 2020). Clinical manifestations are similar to human kidney disease, including elevated serum creatinine and serum urea nitrogen concentrations, reduced creatinine clearance, hypoproteinemia, hypoalbuminemia, proteinuria, and morphological changes in kidney damage (Lee and Harris, 2011;Khajavi-Rad et al, 2017;Li et al, 2019). Histopathological changes of nephrotoxicity appear as early as one to two weeks after DXR administration and progress to a severe stage by four weeks (Wang et al, 2000;Lee and Harris, 2011).…”

“…Unravelling the mechanistic pathways of DXR nephrotoxicity remains quite challenging due to different clinical presentations of the model, such as acute kidney injury, acute tubular necrosis, nephrotic syndrome, chronic kidney injury, and other types of nephropathies (Okuda et al, 1986;Li et al, 2019;Molehin, 2020). The rationale behind the variability in clinical response might be the narrow therapeutic index of the drug leading to a significant variation in disease severity with a small difference in the dose administered.…”