Novel role of Zn(II)-curcumin in enhancing cell proliferation and adjusting proinflammatory cytokine-mediated oxidative damage of ethanol-induced acute gastric ulcers

Chem Biol Interact. 2012 Apr 15;197(1):31-9. doi: 10.1016/j.cbi.2012.03.006. Epub 2012 Mar 20.

Abstract

Alcohol consumption can induce gastric ulcers and zinc deficiency. Zinc complexes were reported to have anti-ulcer activity as it acts as an anti-inflammatory and antioxidant. Zn(II)-curcumin complex and its solid dispersions (SDs) were synthesized and evaluated for its gastroprotective activity and mechanism against ethanol-induced ulcer. The Swiss murine fibroblast cell line (3T3) was used as an alternative in vitro model to evaluate the effects of Zn(II)-curcumin on cell proliferation. Zn(II)-curcumin were administered orally for seven consecutive days prior to induction of ulcers using ethanol. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that solid dispersions (SDs) of Zn(II)-curcumin (2.5-20 μM) enhanced the proliferation of 3T3 cells more significantly than curcumin at the same concentrations (P<0.01). Oral administration of Zn(II)-curcumin (12, 24 and 48 mg/kg) SDs dose-dependently prevented formation of ulcer lesions induced by ethanol. The levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and oxidative stress superoxide dismutase (SOD), glutathione peroxidase (GPX-Px), malonaldehyde (MDA) and H(+)-K(+)-ATPase were in the rats exposed to ethanol in ulceration have been altered. Zn(II)-curcumin prevented formation of ulcer lesions, significantly inhibited TNF-α and IL-6 mRNA expression, increased the activity of SOD and GSH-Px, reduced MDA levels and H(+)-K(+)-ATPase in mucosa of rats compared to controls (P<0.05). These findings suggest that the gastroprotective activity of Zn(II)-curcumin complex might contribute in stimulating cell proliferation and adjusting the proinflammatory cytokine-mediated oxidative damage to the gastric mucosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Alcohol Drinking / adverse effects
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / chemistry
  • Antioxidants / therapeutic use
  • Cell Proliferation / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / therapeutic use*
  • Curcumin / chemistry
  • Curcumin / therapeutic use*
  • Cytokines / immunology*
  • Ethanol / adverse effects*
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / immunology
  • Gastric Mucosa / pathology
  • Interleukin-6 / immunology
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Stomach Ulcer / chemically induced*
  • Stomach Ulcer / drug therapy*
  • Stomach Ulcer / immunology
  • Stomach Ulcer / pathology
  • Tumor Necrosis Factor-alpha / immunology
  • Zinc / chemistry
  • Zinc / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Coordination Complexes
  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Ethanol
  • Curcumin
  • Zinc