Gastrin-releasing peptide receptor antagonist or N-acetylcysteine combined with omeprazol protect against mitochondrial complex II inhibition in a rat model of gastritis.
The pathophysiology of gastritis involves an imbalance between gastric acid attack and mucosal defence. In addition, the gastric mucosal injury results in adenosine triphosphate (ATP) depletion leading to mitochondrial dysfunction. Several studies have shown the association of mitochondrial disorders with gastrointestinal dysfunction. In the present study, we investigated the activity of mitochondrial respiratory chain complexes activity in the stomach of rats with gastritis induced by indomethacin (IDM) and treated with omeprazole (OM), N-acetylcysteine (NAC) and the gastrin-releasing peptide receptor (GRPR) antagonist RC-3095. Adult male Wistar rats were pre-treated for 7 days with OM, NAC, RC-3095, combination of OM plus RC-3095, OM plus NAC and water (control). The animals were then submitted to fasting for 24 hr; IDM was administered. The rats were killed 6 hr later, and the stomachs were used for evaluation of macroscopic damage and respiratory chain activity. Our results showed that complex I and IV activities were not affected by administration of IDM. On the other hand, complex II and III activities were inhibited. In addition, OM plus RC-3095 and OM plus NAC did not reverse complex II activity inhibition. However, the complex III activity inhibition was reversed only with the combined use of OM plus RC-3095 and OM plus NAC. Our results are in agreement with previous studies indicating mitochondrial dysfunction in the pathophysiology of gastrointestinal tract disease and we suggest that GRPR antagonism might be a novel therapeutic strategy in gastritis.
Laboratory of Experimental Pathophysiology, Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil.
Gislaine T
GT
Rezin
Fabricia C
FC
Petronilho
João H
JH
Araújo
Cinara L
CL
Gonçalves
Juliana F
JF
Daufenbach
Mariane R
MR
Cardoso
Rafael
R
Roesler
Gilberto
G
Schwartsmann
Felipe
F
Dal-Pizzol
Emilio L
EL
Streck
D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004579:Electron Transport / Q000187:drug effects; D042963:Electron Transport Complex II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009853:Omeprazole / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*; D012720:Severity of Illness Index; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013276:Stomach Ulcer / Q000517:prevention & control
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D010446:Peptide Fragments; D054328:Proton Pump Inhibitors; D018004:Receptors, Bombesin; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III; D009853:Omeprazole; D001839:Bombesin; D000111:Acetylcysteine; D007213:Indomethacin