THE EFFECT OF HISTAMINE H4 RECEPTOR ANTAGONIST JNJ7777120 ON EXPERIMENTAL ULCER MODELS IN RATS


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Kaltuş Z., Harmancı N., Eroğlu E., Özatik O., Yıldırım E.

2 nd INTERNATIONAL AND 27th NATIONAL PHARMACOLOGY CONGRESS, Antalya, Türkiye, 23 - 26 Kasım 2023, ss.371-372

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Antalya
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.371-372
  • Eskişehir Osmangazi Üniversitesi Adresli: Evet

Özet

Objectives: Gastric ulcer is one of the most common diseases of the gastrointestinal tract. Alcohol, psychological stress, Helicobacter pylori and nonsteroidal anti-inflammatory(NSAID) drugs are among the most common causes. H4R antagonists are being developed as new anti-allergic and anti-inflammatory drugs. Our study aimed to investigate the gastroprotective effect of the H4R antagonist JNJ7777120 on gastric damage caused by ethanol, indomethacin and LPS. Materials-Methods: 63 male Sprague Dawley rats were randomly divided into 9 groups(n = 7). Control group (saline), Ethanol group(Absolute,1 ml), Ethanol+JNJ7777120 group ethanol(Absolute,1 ml)+ JNJ7777120(10 mg/kg), Indomethacin group(40 mg/kg), indomethacin +JNJ7777120 group indomethacin( 40 mg/kg)+ JNJ7777120 (10 mg/kg), Stress group, Stress+JNJ7777120 group(10 mg/kg), LPS group serotype(O26:B6) 1 mg/kg/day for 3 consecutive days, LPS+JNJ7777120 group LPS 1 mg/kg/day+ JNJ7777120(10 mg/kg/day) were administered for 3 consecutive days. Samples were taken from the stomach corpus and fundus parts for biochemical and histomorphological studies. For statistical evaluations, the Kruskal Wallis test was performed using SPSS 21.0. P<0.05 was considered significant. Results: According to histologic assessment significant gastritis and damage were detected in the indomethacin group. Gastric histology was close to normal in the indomethacin+JNJ7777120 group. Severe mucosal damage and gastritis were observed in the ethanol group. Weak and moderate gastritis findings were observed in the Ethanol+JNJ group. Weak grade gastritis was observed in the LPS group. In the LPS+JNJ group, hemorrhagic spots were present as weak gastritis findings. Caspase, NF-kb and TNF-α levels were significantly decreased in JNJ+ ethanol and JNJ+indomethacin groups compared to their control groups (p<0.001 and p<0.01). Catalase levels were significantly decreased in JNJ+ ethanol and JNJ+indomethacin groups compared to their control groups and the main control group. SOD levels were significantly increased in JNJ+indomethacin group compared to its control group(p<0.05). Conclusion: In our study, JNJ777120 was observed to have a gastroprotective effect in ulcer models induced by ethanol and indomethacin. In future studies, it would be useful to apply different doses for the protective effect of JNJ7777120 on gastric damage caused by LPS.

Supported by the Scientific Research Projects Commission (202011035)

Keywords: JNJ7777120, Ulcer, indomethacin, ethanol, LPS