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, 10 (5), 749-56

PMK-S005 Alleviates Age-Related Gastric Acid Secretion, Inflammation, and Oxidative Status in the Rat Stomach

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PMK-S005 Alleviates Age-Related Gastric Acid Secretion, Inflammation, and Oxidative Status in the Rat Stomach

Yoon Jeong Choi et al. Gut Liver.

Abstract

Background/aims: The aim of this study was to evaluate the effect of the synthetic S-allyl-L-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats.

Methods: The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and

Nad(p)h: quinone oxidoreductase 1 (NQO-1), were also measured.

Results: As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX- 2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats.

Conclusions: These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach.

Keywords: Aging; Anti-inflammation; Antioxidants; Gastric acid; s-allyl-L-cysteine.

Figures

Fig. 1
Fig. 1
The effect of PMK-S005 on gastric acid secretion in aging rats. (A) Basal and stimulated acid concentration corrected by body weight. (B) The volume of gastric acid secretion. (C) The pH of gastric acid. The results are expressed as the means±SEM. PMK5, 5 mg/kg of PMK-S005; PMK10, 10 mg/kg of PMK-S005; Lanso, 5 mg/kg of Lansoprazole. *p<0.05 compared with the 6-week-old controls; p<0.05 compared with the 31-week-old controls; p<0.05 compared with the 74-week-old controls; §p<0.05 compared with the 2-year-old controls.
Fig. 2
Fig. 2
Connective tissue area in the laminar propria. (A) Histological changes in the gastric mucosa demonstrated by hematoxylin and eosin staining (magnification, ×200). The arrows indicate the thickness of the connective tissue. (B) The connective tissue area was measured using a computerized video analysis system (Image-Pro Plus 7.0; Media Cybernetic). The results are expressed as the means±SEM of seven animals per group. PMK5, 5 mg/kg of PMK-S005; PMK10, 10 mg/kg of PMK-S005; Lanso, 5 mg/kg of Lansoprazole; LP, lamina propria. *p<0.05 compared with the 6-week-old controls; p<0.05 compared with the 31-week-old controls; p<0.05 compared with the 74-week-old controls; §p<0.05 compared with the 2-year controls.
Fig. 3
Fig. 3
Effect of PMK-S005 on the levels of proinflammatory cytokines and COX-2 expression with aging. The mucosal levels of tumor necrosis factor α (TNF-α) (A) and interleukin 1β (IL-1β) (B) were determined using an enzyme-linked immunosorbent assay. COX-2 protein expression in the gastric mucosa was evaluated by Western blot analysis (C). A representative Western blot assay is shown (D). The results are expressed as the means±SEM of five animals per group. PMK5, 5 mg/kg of PMK-S005; PMK10, 10 mg/kg of PMK-S005; Lanso, 5 mg/kg of Lansoprazole. *p<0.05 compared with the 6-week-old controls; p<0.05 compared with the 31-week-old controls; p<0.05 compared with the 74-week-old controls; §p<0.05 compared with the 2-year-old controls.
Fig. 4
Fig. 4
PMK-S005 relieves the age-related decrease in antioxidant enzymes. Western blot analysis of heme oxyganase 1 (HO-1) (A) and NAD(P) H:quinone oxidoreductase 1 (NQO-1) (B) levels in the rat gastric mucosa. A representative Western blot is shown (C, D). The results are expressed as the means±SEM of five animals per group. PMK5, 5 mg/kg of PMK-S005; PMK10, 10 mg/kg of PMK-S005; Lanso, 5 mg/kg of Lansoprazole. *p<0.05 compared with the 6-week-old controls; p<0.05 compared with the 74-week-old controls.

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