Protective effect of empagliflozin on gentamicin-induced acute renal injury via regulation of SIRT1/NF-κB signaling pathway

Environ Toxicol Pharmacol. 2022 Aug:94:103907. doi: 10.1016/j.etap.2022.103907. Epub 2022 Jun 11.

Abstract

Gentamicin is a highly effective antibiotic. However, its major complication is nephrotoxicity. This study investigated the beneficial effects of empagliflozin against gentamicin-induced nephropathy. Kidney damage was induced in male Wistar rats by administration of gentamicin (100 mg/kg/day, i.p.) for 8 days. Two doses of empagliflozin (10 and 20 mg/kg, p.o.) were concomitantly given with gentamicin for 8 days. Gentamicin administration increased serum creatinine, urea, and cystatin C concentrations. Empagliflozin in both doses ameliorated these changes via mitigation of gentamicin-induced increase in renal oxidative stress, inflammation, and apoptosis. Empagliflozin added to GM treatment led to lower measured levels of TGF-B, NF-κB and caspase 3, and only the higher dose increased PAX2 levels indicating an improvement in tubular regeneration. Additionally, empagliflozin (20 mg/kg/day) markedly prevented gentamicin-induced histopathological changes. The protective effects of empagliflozin may be mediated by decreasing gentamicin concentration in renal tissue and possibly other effects like antioxidant and antiapoptotic effects.

Keywords: Empagliflozin; Gentamicin; Nephrotoxicity; Rats; Sodium glucose cotransporter-2 (SGLT-2) inhibitor.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / drug therapy
  • Acute Kidney Injury* / prevention & control
  • Animals
  • Benzhydryl Compounds
  • Gentamicins* / toxicity
  • Glucosides
  • Kidney
  • Male
  • NF-kappa B / metabolism
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Sirtuin 1 / metabolism

Substances

  • Benzhydryl Compounds
  • Gentamicins
  • Glucosides
  • NF-kappa B
  • Sirt1 protein, rat
  • Sirtuin 1
  • empagliflozin