Elucidation of protective effects of oxime derivatives against cisplatin-induced cytotoxicity in LLC-PK1 kidney cells

Bioorg Med Chem Lett. 2023 Jan 15:80:129114. doi: 10.1016/j.bmcl.2022.129114. Epub 2022 Dec 24.

Abstract

This study aimed to explore the renoprotective effects of oxime derivatives against cisplatin-mediated cell death in LLC-PK1 porcine kidney epithelial cells. Treatment with compounds 161-A and 161-F improved cisplatin-mediated LLC-PK1 cell damage and increased cell viability by more than 80% of the control value when compared with that of cisplatin-treated cells. In addition, 161-A and 161-F reduced cisplatin-induced apoptosis. Analysis of the molecular mechanisms underlying the effects exerted by these compounds revealed that treatment with 161-A and 161-B inhibited the protein expression of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) and cleaved caspase-3 in cisplatin-treated LLC-PK1 cells. Thus, these findings provide in vitro scientific evidence that oxime derivatives may be useful as pharmacological candidates for the prevention of cisplatin-mediated nephrotoxicity.

Keywords: Apoptosis; LLC-PK1 cells; Nephrotoxicity cisplatin; Oxime derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cisplatin* / pharmacology
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Kidney* / metabolism
  • LLC-PK1 Cells
  • Swine

Substances

  • Cisplatin
  • JNK Mitogen-Activated Protein Kinases