Gastroprotective Effects of PMK-S005 against Ethanol-Induced Acute Gastric Damage in Rats.
OBJECTIVE
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.
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Yoon Jeong
YJ
Choi
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.|Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Nayoung
N
Kim
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Ju Yup
JY
Lee
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Ryoung Hee
RH
Nam
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Ji Hyung
JH
Seo
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Seonmin
S
Lee
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Hee Jin
HJ
Kim
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Yoon Jin
YJ
Choi
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
Hye Seung
HS
Lee
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.|Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Dong Ho
DH
Lee
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects; D005756:Gastritis / Q000517:prevention & control; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006595:Hexosamines / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007509:Irritants / Q000633:toxicity; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005765:Gastrointestinal Agents; D006595:Hexosamines; D053583:Interleukin-1beta; D007509:Irritants; C000594566:PMK-S005; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D009195:Peroxidase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D054510:Phospholipases A2, Cytosolic
Anti-inflammation; Antioxidants; Ethanol; Gastroprotection; S-allyl-L-cysteine