Gastroprotective effects of L-lysine salification of ketoprofen in ethanol-injured gastric mucosa

J Cell Physiol. 2015 Apr;230(4):813-20. doi: 10.1002/jcp.24809.

Abstract

Ketoprofen L-lysine salt (KLS), a NSAID, is widely used for its analgesic efficacy and tolerability. L-lysine salification was reported to increase the solubility and the gastric absorption and tolerance of ketoprofen. Since the management of NSAIDs gastrotoxicity still represents a major limitation in prolonged therapies, mainly when gastric lesions are present, this study investigated the gastro-protective activity of L-lysine by using a well-established model of gastric mucosa injury, the ethanol-gastric injury model. Several evidences show that the damaging action of ethanol could be attributed to the increase of ROS, which plays a key role in the increase of lipid peroxidation products, including malonyldialdehyde and 4-hydroxy-2-nonenal. With the aim to unravel the mechanism of L-lysine gastroprotection, cellular MDA levels and 4-HNE protein adducts as markers of lipid peroxidation and a panel of key endogenous gastro-protective proteins were assayed. The data obtained indicate a gastroprotective effect of L-lysine on gastric mucosa integrity.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cells, Cultured
  • Ethanol / pharmacology*
  • Gastric Mucosa / metabolism*
  • Humans
  • Ketoprofen / analogs & derivatives*
  • Ketoprofen / metabolism
  • Ketoprofen / pharmacology
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / physiology
  • Lysine / analogs & derivatives*
  • Lysine / metabolism
  • Lysine / pharmacology
  • Nitric Oxide / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Nitric Oxide
  • Ethanol
  • ketoprofen lysine
  • Ketoprofen
  • Lysine