Carvedilol attenuates inflammatory biomarkers and oxidative stress in a rat model of ulcerative colitis

Drug Dev Res. 2015 Jun;76(4):204-14. doi: 10.1002/ddr.21256.

Abstract

Preclinical Research This study evaluated the effects of the carvedilol, a nonselective β-adrenoceptor anatgonist with α1-adrenoceptor antagonist activity, in a rat model of experimentally induced ulcerative colitis (UC). UC was produced using acetic acid (AA) in animals previously treated with carvedilol (30 mg/kg po, qd) for seven days. Mucus content, lipid peroxidation (LPO) products, sulfhydryl groups, antioxidant enzyme activities, proinflammatory cytokines, prostaglandin E2 and nitric oxide levels were measured in colonic tissues and histopathological changes were assessed. LPO and proinflammatory biomarkers were markedly increased, while mucus content, sulfhydryl groups and enzymatic activities were inhibited in animals administered AA. Pretreatment with carvedilol attenuated LPO elevation, mucus content and sulfhydryl group inhibitions. Antioxidant enzymatic activity and proinflammatory biomarker levels were also restored in carvedilol-pretreated animals. Colonic protection associated with carvedilol pretreatment was further confirmed by histopathological assessment and found to be similar to the standard therapy of mesalazine (100 mg/kg po qd), suggesting that the effects of carvedilol action may be attributable to its anti-inflammatory and antioxidant properties.

Keywords: carvedilol; inflammatory bowel disease; oxidative stress; ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Biomarkers / metabolism
  • Carbazoles / pharmacology
  • Carbazoles / therapeutic use*
  • Carvedilol
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / metabolism
  • Colon / metabolism
  • Cytokines / metabolism
  • DNA / metabolism
  • Dinoprostone / metabolism
  • Disease Models, Animal
  • Male
  • Malondialdehyde / metabolism
  • Mucus / metabolism
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • Propanolamines / pharmacology
  • Propanolamines / therapeutic use*
  • RNA / metabolism
  • Rats, Wistar
  • Sulfhydryl Compounds / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Biomarkers
  • Carbazoles
  • Cytokines
  • Propanolamines
  • Sulfhydryl Compounds
  • Carvedilol
  • Nitric Oxide
  • Malondialdehyde
  • RNA
  • DNA
  • Dinoprostone