Gastrin-Releasing Peptide Receptor Antagonist or N-acetylcysteine combined with Omeprazol Protect against Mitochondrial Complex II Inhibition in a Rat Model of Gastritis

Abstract

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.

The prospective curative role of lipoxin A4 in induced gastric ulcer in rats: Possible involvement of mitochondrial dynamics signaling pathway

“…The exact mechanism by which Omez suppressed mitochondrial ROS is not well known, but it could be explained by it direct effect on mitochondrial ROS . Omez failed to correct the reduction of complex‐I activity which was in accordance with a previous research study …”

“…40 Omez failed to correct the reduction of complex-I activity which was in accordance with a previous research study. 41 Our results exhibited that IND significantly reduced gastric PGE 2 . These findings were matched with those reported by the previous investigators.…”

Insights into bombesin receptors and ligands: Highlighting recent advances

“…This proposal was made because Bn- related peptides and/or activation of BnRs has been shown to play an important role in various inflammatory processes. Evidence supports a role for Bn related peptides and their receptors in a wide spectrum of inflammatory processes including gastritis [263,264,266,288], uveitis [260,264,266], arthritis [98,100,10,251,252,264,266], small intestinal or colonic inflammation [5,12,104,264,266], experimental sepsis [52,61,264,266,267], acute lung inflammation and injury [59,65,264,266,266,341] and gastrointestinal inflammation [10,151,264,266]. These studies suggest BnRs plays different roles in these processes because in some inflammatory processes Bn/GRP is protective and ameliorates the damage from various noxious agents in the stomach, small intestine and in the colon [5,9,12,104,264,266,284], whereas in other inflammatory conditions of the colon or lung, either Bn/GRP stimulate the inflammation or Bn/GRP antagonists ameliorate the inflammation [59,62,65,260,264,266,341,382].…”

GRP/GRPR enhances alcohol-associated liver injury through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway

“…[15] Interestingly, GRPR has also been found to be expressed primarily in immune cells and mediate chemotaxis in neutrophils. [16] GRPR antagonists have anti-inflammatory effects in multiple diseases, including sepsis, [17] arthritis, [18] hepatic ischemia/reperfusion injury, [19] gastritis, [20] and asthma. [21] GRP/GRPR is associated with inflammatory responses and is a potential therapeutic target for various diseases related to inflammation.…”