Gastroprotective Effects of PMK-S005 against Ethanol-Induced Acute Gastric Damage in Rats

Gut Liver. 2016 May 23;10(3):348-55. doi: 10.5009/gnl14509.

Abstract

Background/aims: This study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-Lcysteine (SAC; a sulfur-containing amino acid), against acute ethanol-induced gastric damage in rats.

Methods: Sprague- Dawley rats were divided into six groups, including a nonethanol group, groups treated with absolute ethanol 1 hour after pretreatment with various doses of PMK-S005 (1, 5, and 10 mg/kg) or rebamipide (50 mg/kg), and an absolute ethanolonly group. Ethanol-induced gross ulcer and mucus levels were measured. Myeloperoxidase, tumor necrosis factor a, interleukin 1β, PGE₂, LTB₄, cPLA₂, COX-1, and COX-2 levels were estimated by enzyme-linked immunosorbent assay or Western blot analysis. Furthermore, the protein expression levels of antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)Hquinine oxidoreductase 1 (NQO-1), GCLC, and GCLM, were assessed.

Results: PMK-S005 significantly attenuated the ethanol-induced gastric damage; it reduced mucosal inflammatory cytokine production and increased mucus levels. The expression levels of cPLA₂, COX-1, and COX-2 were decreased by PMK-S005. PMK-S005 did not affect PGE₂ synthesis, but LTB₄ production was significantly suppressed. In addition, long-term administration of PMKS005 significantly increased the expression of HO-1, NQO-1, GCLC, and GCLM.

Conclusions: These results strongly suggest that PMK-S005 prevents gastric mucosal damage and that these gastroprotective activities are due to anti-inflammatory effects and enhancement of the gastric defense system, including antioxidant enzymes.

Keywords: Anti-inflammation; Antioxidants; Ethanol; Gastroprotection; S-allyl-L-cysteine.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology
  • Blotting, Western
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Ethanol / toxicity
  • Gastric Mucosa / drug effects
  • Gastritis / prevention & control
  • Gastrointestinal Agents / pharmacology*
  • Hexosamines / metabolism
  • Interleukin-1beta / metabolism
  • Irritants / toxicity
  • Male
  • Peroxidase / metabolism
  • Phospholipases A2, Cytosolic / metabolism
  • Plant Extracts / pharmacology*
  • Rats, Sprague-Dawley
  • Stomach / drug effects*
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / prevention & control
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Gastrointestinal Agents
  • Hexosamines
  • Interleukin-1beta
  • Irritants
  • PMK-S005
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Ethanol
  • Peroxidase
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Phospholipases A2, Cytosolic