Work

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

Year: 2025

Type: article

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.

Source: BioMed Research International

DOI: 10.1155/bmri/3520935

Authors: Jiaxu Wu, Xikun Wu, Wenli Li, Yakun Zhang, Zhiqing Zhang

Institutions: Hebei Medical University, Second Hospital of Hebei Medical University

Language: English

Topic: Acute Kidney Injury Research

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $2,680