Gut Liver.  2016 May;10(3):348-355. 10.5009/gnl14509.

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

• Choi YJ
• Kim N
• Lee JY
• Nam RH
• Seo JH
• Lee S
• Kim HJ
• Choi YJ
• Lee HS
• Lee DH

• KMID: 2411960
• DOI: http://doi.org/10.5009/gnl14509

Abstract

BACKGROUND/AIMS
This study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-L-cysteine (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 ethanol-only group. Ethanol-induced gross ulcer and mucus levels were measured. Myeloperoxidase, tumor necrosis factor α, 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)H:quinine 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 PMK-S005 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.

Keyword

S-allyl-L-cysteine; Gastroprotection; Anti-inflammation; Antioxidants; Ethanol

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/prevention & control
Tumor Necrosis Factor-alpha/metabolism
Anti-Inflammatory Agents
Antioxidants
Gastrointestinal Agents
Hexosamines
Interleukin-1beta
Irritants
Plant Extracts
Tumor Necrosis Factor-alpha
Ethanol
Cyclooxygenase 1
Cyclooxygenase 2
Phospholipases A2, Cytosolic