Key result
Dioscorea bulbifera worsens doxorubicin cardiotoxicity and lowers survival by blocking P-glycoprotein-mediated drug excretion.
Why the study?
The effect of Dioscorea bulbifera on doxorubicin pharmacokinetics and toxicity, particularly via P-glycoprotein inhibition, was unclear.
Potential herb-drug interaction warrants clinical vigilance with doxorubicin; leaves open human pharmacokinetic confirmation.
(DB) solution in mice, and to explore the effect of P-glycoprotein (P-gp) on this type of DDI. The toxicity of DOX in the liver, kidneys, and heart was assessed with alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), urea nitrogen (BUN), creatine kinase MB (CK-MB), creatine kinase (CK) and histopathology. High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was used to determine the concentrations of DOX in the serum, liver, kidneys and heart. Immunohistochemistry and western blots were used to determine the expression levels of P-gp in these tissues. Our results demonstrated that, after co-administration of DOX and DB, survival was significantly decreased compared with either administration of DOX or DB alone, or water. Co-administration of DOX and DB induced elevated levels of toxicity in the heart and kidneys, but not the liver, compared with DOX alone. We conclude that concurrent treatment with DOX and DB results in increased levels of toxicity due to the accumulation of DOX in the body. Delayed excretion of DOX is associated with inhibition of P-gp in liver and kidneys.
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Qu et al. (2018) studied Doxorubicin-induced cardiotoxicity and nephrotoxicity. Dioscorea bulbifera L. and doxorubicin co-administration vs. Doxorubicin alone, Dioscorea bulbifera L. alone, or water was evaluated on Survival and organ toxicity (heart, kidneys, and liver). Co-administration of Dioscorea bulbifera L. and doxorubicin significantly decreased survival and aggravated cardiotoxicity and nephrotoxicity in mice compared to doxorubicin alone by delaying drug excretion via P-glycoprotein inhibition.
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