Protective effects of vitamin D3 (cholecalciferol) on vancomycin-induced oxidative nephrotoxic damage in rats

Pharm Biol. 2023 Dec;61(1):755-766. doi: 10.1080/13880209.2023.2204916.

Abstract

Context: Vancomycin (VCM), an important antibiotic against refractory infections, has been used to treat secondary infections in severe COVID-19 patients. Regrettably, VCM treatment has been associated with nephrotoxicity. Vitamin D3 can prevent nephrotoxicity through its antioxidant effect.

Objective: This study tests the antioxidant effect of vitamin D3 in the prevention of VCM-induced nephrotoxicity.

Materials and methods: Wistar Albino rats (21) were randomly divided into 3 groups: (A) control; (B) VCM 300 mg/kg daily for 1 week; and (C) VCM plus vitamin D3 500 IU/kg daily for 2 weeks. All the rats were sacrificed and serum was separated to determine kidney function parameters. Their kidneys were also dissected for histological examination and for oxidative stress markers.

Results: Lipid peroxidation, creatinine, and urea levels decreased significantly (p < 0.0001) in the vitamin D3-treated group (14.46, 84.11, 36.17%, respectively) compared to the VCM group that was given VCM (MIC<2 μg/mL) only. A significant increase was observed in superoxide dismutase levels in the vitamin D3-treated group (p < 0.05) compared to rats without treatment. Furthermore, kidney histopathology of the rats treated with vitamin D3 showed that dilatation, vacuolization and necrosis tubules decreased significantly (p < 0.05) compared with those in the VCM group. Glomerular injury, hyaline dystrophy, and inflammation improved significantly in the vitamin D3 group (p < 0.001, p < 0.05, p < 0.05, respectively) compared with the VCM group.

Discussion and conclusions: Vitamin D3 can prevent VCM nephrotoxicity. Therefore, the appropriate dose of this vitamin must be determined, especially for those infected with COVID-19 and receiving VCM, to manage their secondary infections.

Keywords: COVID-19; creatinine; kidney function; lipid peroxides; nephrotoxicity; oxidative stress; superoxide dismutase; urea.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • COVID-19* / metabolism
  • Cholecalciferol / metabolism
  • Cholecalciferol / pharmacology
  • Coinfection* / metabolism
  • Coinfection* / pathology
  • Kidney
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Vancomycin / toxicity

Substances

  • Vancomycin
  • Antioxidants
  • Cholecalciferol

Grants and funding

This study was funded by Damascus University, Faculty of Pharmacy, Damascus, Syria.