Elevated Pro-inflammatory Cytokine Levels in Acute Reflux Esophagitis Are Reduced by 1,25 Dihydroxy Vitamin D3.

BACKGROUND/AIM: Gastric acid reflux into the esophagus can cause irritation and inflammation of the esophagus and progress to reflux esophagitis (RE). Vitamin D3 (VitD3) has anti-inflammatory effects and plays an important regulatory role in adaptive and innate immunity. We hypothesized that VitD3 may play a protective role in RE. MATERIALS AND METHODS: Seventy male Sprague-Dawley rats were used, and acute RE (n=35) or chronic RE (n=35) were surgically induced. The effects of different doses of VitD3 on morphological changes and alteration of pro-inflammatory cytokine levels were examined in the rat models. Western blot analysis was performed to determine protein expression levels of IL-1ß, IL-6, and IL-8 in esophageal tissues. Serum levels of VitD3 and calcium were determined using enzyme-linked immunosorbent assays. RESULTS: The protein expression of pro-inflammatory cytokines IL-1ß, IL-6, and IL-8 was found significantly increased in RE. VitD3 treatment significantly reduced the levels of these pro-inflammatory cytokines in both the low-dose and high-dose VitD3 groups compared to control groups in acute RE, but not chronic RE. Macrographic and histopathological examination revealed various degrees of esophageal impairment in rats following surgical induction of acute or chronic RE in rats. These impairments were not improved by VitD3. Morphological grading of esophageal mucosa showed no significant differences between acute and chronic RE. Elevated serum levels of calcium were observed after VitD3 treatment. CONCLUSION: IL-1ß, IL-6, and IL-8 levels were significantly elevated in RE. The abnormal increase in these important pro-inflammatory cytokines was suppressed by VitD3 in the rat models of acute RE. These novel findings suggest a potential protective role of VitD3 in early-stage RE.

Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats with Reflux Esophagitis.

BACKGROUND We designed this study to investigate the influence of different ratios of n-6/n-3 polyunsaturated fatty acid in the diet of reflux esophagitis (RE) rats' and the effect on the PI3K/Akt pathway. MATERIAL AND METHODS RE rats were randomly divided into a sham group and modeling groups of different concentrations of n-6/n-3 polyunsaturated fatty acid (PUFA): 12:1 group, 10:1 group, 5:1 group, and 1:1 group. RT-PCR and Western-blot were used to detect the expression of PI3K, Akt, p-Akt, NF-κBp50, and NF-κBp65 proteins in esophageal tissue. RESULTS In the n-6/n-3 PUFAs groups the expression of PI3K, Akt, p-Akt, nf-κbp50, and NF-κBp65 mRNA decreased with the decrease in n-6/n-3 ratios in the diet. The lowest expression of each indicator occurred in the 1:1 n-6/n-3 group compared with other n-6/n-3 groups, the difference was statistically significant (p<0.05). CONCLUSIONS The inhibition of n-3 PUFAs in the development of esophageal inflammation in rats with RE was attributed to the function of PI3K/Akt-NF-κB signaling pathway.

The effect of n-3/n-6 polyunsaturated fatty acids on acute reflux esophagitis in rats.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) play various roles in inflammation. However, the effect of PUFAs in the development of reflux esophagitis (RE) is unclear. This study is to investigate the potential effect of n-3/n-6 PUFAs on acute RE in rats along with the underlying protective mechanisms. METHODS: Forty Sprague Dawley rats were randomly divided into four groups (n = 10 in each group). RE model was established by pyloric clip and section ligation. Fish oil- and soybean oil-based fatty emulsion (n-3 and n-6 groups), or normal saline (control and sham operation groups) was injected intraperitoneally 2 h prior to surgery and 24 h postoperatively (2 mL/kg, respectively). The expressions of interleukin (IL)-1ß, IL-8, IL-6 and myeloid differentiation primary response gene 88 (MyD88) in esophageal tissues were evaluated by Western blot and immunohistochemistry after 72 h. The malondialdehyde (MDA) and superoxide dismutase (SOD) expression in the esophageal tissues were determined to assess the oxidative stress. RESULTS: The mildest macroscopic/microscopic esophagitis was found in the n-3 group (P < 0.05). The expression of IL-1ß, IL-8, IL-6 and MyD88 were increased in all RE groups, while the lowest and highest expression were found in n-3 and n-6 group, respectively (P < 0.05). The MDA levels were increased in all groups (P < 0.05), in an ascending trend from n-3, n-6 groups to control group. The lowest and highest SOD levels were found in the control and n-3 group, respectively (P < 0.05). CONCLUSION: n-3 PUFAs may reduce acute RE in rats, which may be due to inhibition of the MyD88-NF-kB pathway and limit oxidative damage.

Decreased n-6/n-3 polyunsaturated fatty acid ratio reduces chronic reflux esophagitis in rats.

AIM: To investigate the effect of dietary ratio of n-6/n-3 PUFAs on chronic reflux esophagitis (RE) and lipid peroxidation. METHOD: Rat RE model were established and then fed on a diet contained different n-6/n-3 PUFA ratios (1:1.5, 5:1, 10:1) or received pure n-6 PUFA diet for 14 days. Esophageal pathological changes were evaluated using macroscopic examination and hematoxyline-eosin staining. IL-1ß, IL-8, and TNFα mRNA and protein levels of were determined using RT-PCR and Western blotting, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined using ELISA. RESULTS: The severity of esophagitis was lowest in the PUFA(1:1.5) group (P<0.05). IL-1ß, IL-8, and TNFα mRNA and protein and MDA levels were significantly increased in model groups with the increasing n-6/n-3 PUFA ratios. SOD levels were significantly decreased in all RE PUFA groups (P<0.05). CONCLUSION: Esophageal injury and lipid peroxidation appeared to be ameliorated by increased n-3 PUFAs intake.

[Efficacy of moxifloxacin-based triple therapy to eradicate Helicobacter pylori infection].

OBJECTIVE: To evaluated the efficacy of 9-day moxifloxacin-based triple therapy as first- or second-line treatment to eradicate Helicobacter pylori (H. pylori). METHODS: Three hundred and thirteen H. pylori-positive patients without previous treatment (Group A), 51 Hp-positive patients with once-failed treatment (Group B) and 32 with twice-failed treatment (Group C) were recruited to receive moxifloxacin, esomeprazole and tinidazole (MET) for 9 days.H. pylori status was re-assessed 4 weeks after the end of therapy by urea breath test. The eradication rate and its 95% confidence interval (95%CI) were calculated in intention-to-treat (ITT) and per-protocol (PP) analyses respectively. RESULTS: In ITT analysis, the Hp-eradication rate was 89.8% (95%CI: 86.7% - 93.0%) in Group A, 81.2% (75.3% - 90.9%) in Group B and 81.2% (66.1% - 92.6%) in Group C, among which no significant difference was observed (chi(2) = 4.339, P > 0.05). However, in PP analysis there was a significant difference among them [93.9% (90.9% - 96.4%) in Group A, 84.8% (79.1% - 93.6%) in Group B and 81.2% (66.1% - 92.6%) in Group C (chi(2) = 9.294, P < 0.01)]. The rates were significantly lower respectively in Group B (chi(2) = 4.885, P < 0.05) and in Group C (chi(2) = 7.023, P < 0.01) than that observed in Group A according to PP analysis. But there was no significant difference between the patients with first-treated active ulceration and with first-treated gastritis (chi(2) = 1.670, P > 0.05 in ITT, or chi(2) = 0.030, P > 0.05 in PP analysis). Eradication rate in patients with 3rd-treated gastritis was lower than that in patients with first-treated gastritis according to PP analysis (chi(2) = 8.076, P < 0.01). The compliance rate was 95.99% in all patients. CONCLUSION: Nine-day moxifloxacin-based triple therapy provides an optimal eradication rate with a good compliance as first-line or second-line eradication of Hp.