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Study of Serum Metabolic Biomarkers and Prediction Models of Cantharidin-Induced Nephrotoxicity in Rats Based on
Weina Cheng1, Wenzhong Feng1, Guanghuan Tian1
1School of Pharmacy, Zunyi Medical University, Zunyi, China.
Abstract:
The clinical application of cantharidin (CTD) is seriously limited due to its nephrotoxicity. Therefore, this study aims to investigate sensitive biomarkers for the evaluation and prediction of nephrotoxicity induced by CTD in rat. A total of 80 rats were randomly divided into four groups: control group and three doses of CTD groups. After 0, 1, 5, 15, and 28 days of intragastric administration, rat serum and urine were collected for biochemical indexes, then serum was used for metabolomic analyses, and rat kidney was collected for pathological and ultrastructural observation. The levels of serum crea (Scr), blood urea nitrogen (BUN), urea, urine crea (Ucrea), and urinary microalbumin (UmALB) were significantly increased after administration of different doses of CTD (p < 0.05). Additionally, histopathology and cell ultrastructure observation of kidney showed significant cell inflammatory infiltration and glomerular edema. Seven metabolic biomarkers including 6-hydroxymelatonin were significantly disturbed by CTD. The CatBoost Classifier prediction model was used to establish the CTD nephrotoxicity prediction model, and the prediction accuracy and precision were 0.645 and 0.640, respectively. Moreover, 6-hydroxymelatonin was found to be most useful biomarkers for evaluating the CTD nephrotoxicity. Finally, the seven metabolic biomarkers were found mainly involved in pyruvate metabolism, pantothenate and CoA biosynthesis.
Insights
Cantharidin (CTD) causes kidney damage. This study identified seven metabolic biomarkers, including 6-hydroxymelatonin, to predict CTD-induced nephrotoxicity in rats, aiding in safer clinical applications.
Area of Science:
- Toxicology
- Biochemistry
- Biomarker Discovery
Background:
- Cantharidin (CTD) exhibits therapeutic potential but its clinical use is limited by significant nephrotoxicity.
- Identifying reliable biomarkers is crucial for early detection and management of CTD-induced kidney damage.
Purpose of the Study:
- To investigate sensitive biomarkers for evaluating and predicting CTD-induced nephrotoxicity in a rat model.
- To understand the underlying metabolic disturbances associated with CTD exposure.
Main Methods:
- 80 rats were divided into control and three CTD dose groups.
- Serum and urine biochemical indexes, metabolomic analyses, and kidney histopathology were performed over 28 days.
- A CatBoost Classifier model was employed for nephrotoxicity prediction.
Main Results:
- CTD administration significantly increased serum creatinine (Scr), blood urea nitrogen (BUN), urea, urine creatinine (Ucrea), and urinary microalbumin (UmALB).
- Kidney pathology revealed inflammatory infiltration and glomerular edema.
- Seven metabolic biomarkers, notably 6-hydroxymelatonin, were significantly altered by CTD, with the prediction model achieving 64.5% accuracy.
Conclusions:
- 6-hydroxymelatonin is a promising biomarker for CTD-induced nephrotoxicity.
- The identified metabolic biomarkers are primarily involved in pyruvate metabolism and pantothenate and CoA biosynthesis.
- These findings contribute to developing strategies for safer CTD clinical applications.
