Antioxidant's cytoprotective effects on rotator cuff tenofibroblasts exposed to aminoamide local anesthetics

J Orthop Res. 2015 Jul;33(7):1001-7. doi: 10.1002/jor.22814. Epub 2015 Apr 14.

Abstract

Local anesthetics (LA) are among the drugs most frequently used for musculoskeletal problems, in procedures ranging from diagnosis to postoperative pain control. The cytotoxicity of LA is an emerging area of concern. The purpose of this study was to determine whether cyanidin, an antioxidant, exerts cytoprotective effects against tenofibroblast death induced by LA. Primary cultured human rotator cuff tenofibroblasts were used to evaluate the cytotoxicity of these LA: Ropivacaine (0.075%), Bupivacaine (0.05%), and Lidocaine (0.2%). The effects of cyanidin (100 μg/ml) on the cytotoxicity induced by these LA were investigated. Cell viability, ROS production, caspase-3/7 activity, and expressions of phospho-extracellular signal-regulated kinases (ERK), phospho-p38, phospho-c-Jun N-terminal kinase (JNK), and cleaved PARP-1 were evaluated. Exposure to LA significantly induced cell death (p < 0.001), ROS production (p ≤ 0.04), the activation of caspase-3/7 (p < 0.001), and the increased expressions of phospho-ERK, phospho-p38, phospho-JNK, and cleaved PARP-1. These LA-induced cytotoxic effects were reduced by cyanidin. These data indicate that cyanidin, an antioxidant, has cytoprotective effects against LA-induced cytotoxicity to rotator cuff tenofibroblasts.

Keywords: antioxidant; cyanidin; cytotoxicity; local anesthetics; rotator cuff tenofibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Local / adverse effects*
  • Anthocyanins / therapeutic use*
  • Antioxidants / therapeutic use*
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cells, Cultured
  • Drug Evaluation, Preclinical
  • Enzyme Activation / drug effects
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Humans
  • Middle Aged
  • Mitogen-Activated Protein Kinases / drug effects
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / metabolism
  • Reactive Oxygen Species / metabolism
  • Rotator Cuff / drug effects*

Substances

  • Anesthetics, Local
  • Anthocyanins
  • Antioxidants
  • Reactive Oxygen Species
  • cyanidin
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Mitogen-Activated Protein Kinases
  • Caspase 3
  • Caspase 7