Ojeoksan Ameliorates Cisplatin-Induced Acute Kidney Injury in Mice by Downregulating MAPK and NF-κB Pathways

Int J Mol Sci. 2022 Oct 14;23(20):12254. doi: 10.3390/ijms232012254.

Abstract

Acute kidney injury (AKI) is a major side effect of cisplatin, a crucial anticancer agent. Therefore, it is necessary to develop drugs to protect against cisplatin-induced nephrotoxicity. Ojeoksan (OJS), a traditional blended herbal prescription, is mostly used in Korea; however, there are no reports on the efficacy of OJS against cisplatin-induced AKI. To investigate the reno-protective effect of OJS on AKI, we orally administered 50, 100, and 200 mg/kg of OJS to mice 1 h before intraperitoneal injection with 20 mg/kg of cisplatin. OJS inhibited the increase of blood urea nitrogen (BUN) and serum creatinine (SCr) levels and reduced histological changes in the kidney, like loss of brush borders, renal tubular necrosis, and cast formation. Administration of OSJ reduced the levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. In addition, OJS inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways in cisplatin-induced AKI. These results suggest that OJS attenuates cisplatin-induced AKI by downregulating the MAPK and NF-κB pathways.

Keywords: MAPK; NF-κB; Ojeoksan; acute kidney injury; cisplatin.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / drug therapy
  • Acute Kidney Injury* / metabolism
  • Animals
  • Antineoplastic Agents* / pharmacology
  • Cisplatin / pharmacology
  • Creatinine
  • Cytokines / metabolism
  • Interleukin-6 / metabolism
  • Kidney / metabolism
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • NF-kappa B
  • Cisplatin
  • Mitogen-Activated Protein Kinases
  • Creatinine
  • Interleukin-6
  • Antineoplastic Agents
  • Tumor Necrosis Factor-alpha
  • Cytokines