Gabapentin, a synthetic analogue of gamma aminobutyric acid, reverses systemic acute inflammation and oxidative stress in mice

Inflammation. 2014 Oct;37(5):1826-36. doi: 10.1007/s10753-014-9913-2.

Abstract

The aim of this study was to investigate the potential anti-inflammatory and anti-oxidant effects of gabapentin (GBP) in mice. The anti-inflammatory and anti-oxidant effects were evaluated using various mediators that induce paw edema, peritonitis model, myeloperoxidase (MPO) activity, proinflammatory cytokine levels, glutathione (GSH) consumption, and malondialdehyde (MDA) production in mice. Pretreatment of mice with GBP (1 mg/kg) significantly reduced carrageenan or dextran-induced paw edema (P<0.05) when compared to vehicle group. Adding to this, GBP (1 mg/kg) significantly inhibited paw edema induced by histamine, serotonin, bradikinin, 48/80 compound, and prostaglandin E2. In the carrageenan-induced peritonitis model, GBP significantly decreased total and differential leukocyte counts and reduced the levels of MPO activity in the plantar tissue and IL-1β and TNF-α concentrations in the peritoneal exudate. The same dose of GBP also decreased the MDA concentration and increased the levels of GSH into the peritoneal fluid. In summary, our results demonstrated that GBP exhibited anti-inflammatory activity in mice by reducing the action of inflammatory mediators, neutrophil migration and proinflammatory cytokine levels, and anti-oxidant properties by decreasing the concentration of MDA and increasing the GSH content. These observations raise the possibility that GBP could be used to improve tissue resistance to damage during inflammatory conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Amines / pharmacology
  • Amines / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cyclohexanecarboxylic Acids / pharmacology
  • Cyclohexanecarboxylic Acids / therapeutic use*
  • Edema / chemically induced
  • Edema / drug therapy*
  • Edema / metabolism*
  • Gabapentin
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • Mice
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Random Allocation
  • gamma-Aminobutyric Acid / analogs & derivatives
  • gamma-Aminobutyric Acid / pharmacology
  • gamma-Aminobutyric Acid / therapeutic use*

Substances

  • Amines
  • Anti-Inflammatory Agents
  • Cyclohexanecarboxylic Acids
  • gamma-Aminobutyric Acid
  • Gabapentin