Acute toxicity and gastroprotection studies of a new schiff base derived copper (II) complex against ethanol-induced acute gastric lesions in rats

PLoS One. 2012;7(12):e51537. doi: 10.1371/journal.pone.0051537. Epub 2012 Dec 10.

Abstract

Background: Copper is an essential element in various metabolisms. The investigation was carried out to evaluate acute gastroprotective effects of the Copper (II) complex against ethanol-induced superficial hemorrhagic mucosal lesions in rats.

Methodology/principal findings: Rats were divided into 7 groups. Groups 1 and 2 were orally administered with Tween 20 (10% v/v). Group 3 was orally administered with 20 mg/kg omeprazole (10% Tween 20). Groups 4-7 received 10, 20, 40, and 80 mg/kg of the complex (10% Tween 20), respectively. Tween 20 (10% v/v) was given orally to group 1 and absolute ethanol was given orally to groups 2-7, respectively. Rats were sacrificed after 1 h. Group 2 exhibited severe superficial hemorrhagic mucosal lesions. Gastric wall mucus was significantly preserved by the pre-treatment complex. The results showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE(2)) activities and a decrease in malondialdehyde (MDA) level. Histology showed marked reduction of hemorrhagic mucosal lesions in groups 4-7. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. PAS staining of groups 4-7 showed intense stain uptake of gastric mucosa. The acute toxicity revealed the non-toxic nature of the compound.

Conclusions/significance: The gastroprotective effect of the Copper (II) complex may possibly be due to preservation of gastric wall mucus; increase in PGE(2) synthesis; GSH, SOD, and NO up-regulation of Hsp70 protein; decrease in MDA level; and down-regulation of Bax protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Copper / chemistry
  • Copper / pharmacology
  • Copper / therapeutic use*
  • Dinoprostone / metabolism
  • Ethanol
  • Female
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / enzymology
  • Gastric Mucosa / pathology
  • Glutathione / metabolism
  • Glycoproteins / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Ligands
  • Male
  • Malondialdehyde / metabolism
  • Nitric Oxide / metabolism
  • Protective Agents / chemistry
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Schiff Bases / chemistry
  • Schiff Bases / pharmacology
  • Schiff Bases / therapeutic use*
  • Stomach / drug effects
  • Stomach / pathology*
  • Stomach Diseases / chemically induced
  • Stomach Diseases / drug therapy*
  • Stomach Diseases / enzymology
  • Stomach Diseases / pathology
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / drug therapy
  • Stomach Ulcer / pathology
  • Superoxide Dismutase / metabolism
  • Toxicity Tests, Acute*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antioxidants
  • Glycoproteins
  • HSP70 Heat-Shock Proteins
  • Ligands
  • Protective Agents
  • Schiff Bases
  • bcl-2-Associated X Protein
  • Nitric Oxide
  • Ethanol
  • Malondialdehyde
  • Copper
  • Superoxide Dismutase
  • Glutathione
  • Dinoprostone

Grants and funding

The authors would like to thank the University of Malaya for funding this research, RG373/11HTM and HIR-MOHE (F000009-21001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.