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. 2025 Jul 31:2025:3520935.
doi: 10.1155/bmri/3520935. eCollection 2025.

The Protective Effect of Omeprazole on Vancomycin Cytotoxicity in HK-2 Cells and Renal Injury in Rats

Jiaxu Wu #  1 , Xikun Wu #  1 , Wenli Li  1 , Yakun Zhang  1 , Zhiqing Zhang  1
Affiliations

The Protective Effect of Omeprazole on Vancomycin Cytotoxicity in HK-2 Cells and Renal Injury in Rats

Jiaxu Wu et al. Biomed Res Int. .

Abstract

Objective: Vancomycin is the first-line treatment for MRSA infection, and high plasma concentration can cause nephrotoxicity. The aim of the study was to determine the correlation between intracellular vancomycin concentration and HK-2 cytotoxicity and explore omeprazole's protective effect. Methods: The activity of HK-2 cells was detected, HPLC method was established and verified, and the vancomycin concentrations in the intracellular and extracellular fluids of HK-2 cells were determined. Western blot was used to investigate the expressions of P-glycoprotein (P-gp) and organic cation transporter-2 (OCT-2) transporters. Blood urea nitrogen (BUN), blood creatinine (CRE), N-acetyl-β-d-glucosaminidase (NAG), and kidney injury molecule-1 (KIM-1) of rats in the vancomycin group and drug combination group were determined; the kidney tissue pathological examination and renal injury score were performed. Results: The HPLC method met the requirements for biological sample determination. The cytotoxicity of vancomycin in HK-2 cells was concentration-dependent within 1-20 mg/mL; omeprazole could reduce the intracellular accumulation of vancomycin. Western blot assay confirmed that omeprazole increased intracellular vancomycin efflux by upregulating P-gp expression and inhibited its intracellular transport by downregulating OCT-2 expression. Vancomycin increased renal function indicators and pathological injury score in rats, while there was a significant decrease in the drug combination group, together with alleviated renal tissue damage. Conclusion: Intracellular accumulation of vancomycin can cause damage to HK-2 cells and induce vancomycin-related nephrotoxicity in rats. Omeprazole can reduce vancomycin cytotoxicity by upregulating P-gp expression and inhibiting OCT-2 expression.

Keywords: HK-2 cells; intracellular concentration; omeprazole; rats; vancomycin.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Effects of vancomycin (VCM) and omeprazole (OME) on the survival rate of HK-2 cells. OME5: 5 μg/mL OME; OME50: 50 μg/mL OME; OME100: 100 μg OME; ⁣∗p < 0.05, ⁣∗∗p < 0.01, compared with the control group; ⁣#p < 0.05, compared with the VCM group.
Figure 2
Figure 2
Effects of vancomycin (VCM) and omeprazole (OME) on the morphology of HK-2 cells. (a) Control. (b) 2 mg/mL VCM. (c) 4 mg/mL VCM. (d) 6 mg/mL VCM. (e) 5 μg/mL OME + 4 mg/mL VCM. (f) 50 μg/mL OME + 4 mg/mL VCM. (g) 100 μg/mL OME + 4 mg/mL VCM.
Figure 3
Figure 3
Effect of vancomycin (VCM) on the protein expression of P-gp and OCT-2 in HK-2 cells. VCM 4: 4 mg/mL VCM; VCM 6: 6 mg/mL VCM; VCM 8: 8 mg/mL VCM; OME5: 5 μg/mL OME; OME50: 50 μg/mL OME; OME100: 100 μg/mL OME; ⁣∗p < 0.05, compared with the control group.
Figure 4
Figure 4
Comparison of renal function indicators and renal injury markers in rats. (a) BUN. (b) CRE. (c) NAG. (d) KIM-1. (e) Renal injury score. VAN: 400 mg/kg VAN; VAN + OME: 400 mg/kg VAN + 4 mg/kg OME; ⁣∗p < 0.05, ⁣∗∗p < 0.01 compared to the control group; ⁣#p < 0.05 compared to the VAN group.
Figure 5
Figure 5
The images of the kidneys of rats. (a) Control group. (b) VCM group. (c) Drug combination group.
Figure 6
Figure 6
Pathological sections of kidney tissue of rats. (a) Control group. (b) VCM group. (c) Drug combination group. The red arrow represents vacuolar degeneration, the blue arrow represents watery degeneration, the black arrow represents tubular necrosis, the green arrow represents tubular atrophy, and the purple arrow represents inflammatory cell infiltration.
See this image and copyright information in PMC

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