Protective Effects of DHA-PC against Vancomycin-Induced Nephrotoxicity through the Inhibition of Oxidative Stress and Apoptosis in BALB/c Mice.

The clinical use of glycopeptide antibiotic vancomycin is usually accompanied by nephrotoxicity, limiting its application and therapeutic efficiency. The aim of this study was to investigate the protection of DHA-enriched phosphatidylcholine (DHA-PC) against nephrotoxicity using a model of vancomycin-induced male BALB/c mice with renal injury by measuring death curves, histological changes, and renal function indexes. The addition of DHA in DHA and DHA-PC groups were 300 mg/kg per day on the basis of human intake level in our study. Results indicated that DHA-PC could dramatically extend the survival time of mice, while traditional DHA and PC had no significant effects. Moreover, oral administration of DHA-PC exhibited better effects on reducing vancomycin-induced increases of blood urea nitrogen, creatinine, cystatin C, and kidney injury molecule-1 levels than traditional DHA and PC. DHA-PC significantly delayed the development of vancomycin-induced renal injury, including tubular necrosis, hyaline casts, and tubular degeneration. A further mechanistic study revealed that the protective effect of DHA-PC on vancomycin-mediated toxicity might be attributed to its ability to inhibit oxidative stress and inactivate mitogen-activated protein kinase (MAPK) signaling pathways, which was associated with upregulation of Bcl-2 and downregulation of caspase-9, caspase-3, cytochrome-c, p38, and JNK. These findings suggest that DHA-PC may be acted as the dietary supplements or functional foods against vancomycin-induced nephrotoxicity.