ArticleFrontiers in pharmacology2026
Pharmacokinetics and nephrotoxicity of cisplatin modulated by combination therapy with brusatol.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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Corrections and comments
- Erratum issued
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6 authors.
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Abstract
Ethnopharmacological Relevance: Quassinoid brusatol, isolated from the traditional Chinese medicine Objective: This study focuses on the effects of brusatol on plasma pharmacokinetics, tissue distribution, and nephrotoxicity of cisplatin. Materials and Methods: For the pharmacokinetic study, 120 Kunming mice were randomly assigned to receive cisplatin (10 mg/kg) alone or in combination with brusatol (2 mg/kg). Blood and tissue samples were collected to evaluate the Results: The developed HPLC-MS method demonstrated high precision and accuracy, meeting the requirements for biological sample analysis. Brusatol reduced the plasma concentration of cisplatin, increased the apparent volume of distribution (Vd), and significantly increased cisplatin concentrations in the kidney and lung, particularly in the kidney. Combined with brusatol, serum levels of blood urea nitrogen and creatinine increased, antioxidant indices in kidney tissue decreased, and inflammatory factors increased. Pathological findings revealed increased tubular congestion. Discussion and Conclusion: Brusatol increases renal cisplatin concentrations by altering its pharmacokinetics, intensifying dose-dependent nephrotoxicity. Further development as a chemotherapy sensitizer requires understanding the mechanisms of this effect and optimizing the combined dose.
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