title: Protective effects of garlic extract, PMK-S005, against nonsteroidal anti-inflammatory drugs-induced acute gastric damage in rats.
abstract: BACKGROUND
  PMK-S005 is synthetic s-allyl-L-cysteine (SAC), a sulfur-containing amino acid, which was initially isolated from garlic. The antioxidant and anti-inflammation activities of SAC have been demonstrated in diverse experimental animal models.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the gastroprotective effects of PMK-S005 against NSAIDs-induced acute gastric damage in rats.
  
  
  METHODS
  Eight-week SD rats were pretreated with PMK-S005 (1, 5, or 10 mg/kg) or rebamipide (50 mg/kg) 1 h before administration of NSAIDs including aspirin (200 mg/kg), diclofenac (80 mg/kg), and indomethacin (40 mg/kg). After 4 h, the gross ulcer index, histological index, and gastric mucus level were determined. Myeloperoxidase (MPO), TNF-α, IL-1β, PGE2, and LTB4 levels were estimated in the gastric mucosal tissue by ELISA. Protein expressions of cPLA2, COX-1, and COX-2 were assessed by Western blot analysis.
  
  
  RESULTS
  Pretreatment with PMK-S005 significantly attenuated the NSAIDs-induced gastric damage and increased the gastric mucus level. In addition, PMK-S005 attenuated increases in MPO, TNF-α, and IL-1β production. The expressions of cPLA2 and COX-2 induced by NSAIDs were decreased by PMK-S005 pretreatment. PMK-S005 did not cause suppression of PGE2 synthesis induced by NSAIDs, but LTB4 production was significantly suppressed by PMK-S005. The effects of PMK-S005 were consistently maximized at a concentration of 5 mg/kg, which were frequently superior to those of rebamipide.
  
  
  CONCLUSIONS
  These results strongly suggest that PMK-S005 can be a useful gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, down-regulating cPLA2, COX-2 and LTB4 expression, and increasing the synthesis of mucus.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, Korea, yjchoi3127@gmail.com.
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Choi
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Ju Yup
authors.initials: JY
authors.lastname: Lee
authors.forename: Ryoung Hee
authors.initials: RH
authors.lastname: Nam
authors.forename: Hyun
authors.initials: H
authors.lastname: Chang
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Seo
authors.forename: Kyu Keun
authors.initials: KK
authors.lastname: Kang
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yun Jin
authors.initials: YJ
authors.lastname: Choi
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Lee
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005737:Garlic / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D015363:Quinolones / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; C000594566:PMK-S005; D010936:Plant Extracts; D015363:Quinolones; C052785:rebamipide; D000409:Alanine