The Role of Zileuton in Indomethacin- Induced Gastric Ulceration in Pyloric-Ligated Diabetic Rats

Abstract

Zileuton is an active inhibitor of 5-lipoxygenase, it also inhibits leukotrienes (LTB4, LTC4, LTD4, and LTE4) formation. It has antioxidant and anti-inflammatory properties which renders it an attractive candidate for protection against peptic ulcer. Therefore, this study was performed to assess the protective property of this agent against indomethacin (IND)-induced gastric ulceration in diabetic rats. A total of 36 adult male albino rats were used in the study and divided into 6 groups (6 rats each) into the following groups: normal control group, diabetic control group, diabetic IND group (single intraperitoneal injection of 30 mg/kg), diabetic IND/ omeprazole-treated group (40 mg/kg/day), diabetic IND/ zileuton-treated group (25mg/kg/day), diabetic IND/ omeprazole/ zileuton-treated group. The treated drugs were administered 14 days before pyloric ligation and IND administration to the diabetic rats. Zileuton pretreatment significantly attenuated the gastric mucosal lesions induced by IND administration, decreased the total gastric acidity, and pepsin activity with marked attenuation of the gastric mucosal lipid peroxidation and serum tumor necrosis factor alpha. In addition, zileuton pretreatment significantly increased the activity of both catalase and superoxide dismutase, gastric mucosal levels of nitric oxide and the concentration of mucin in gastric juice in comparison to the diabetic indomethacin-treated rats. Furthermore, zileuton pretreatment had antiapoptotic effect as evident by immunological study of caspase 3. In conclusion, zileuton can be considered a potential therapeutic agent to protect against the major clinical challenge of gastric injury in diabetic rats.

Rivastigmine ameliorates indomethacin experimentally induced gastric mucosal injury via activating α7nAChR with inhibiting oxidative stress and apoptosis

“…[42] IND promotes inflammation by triggering macrophages to produce inflammatory cytokines such as TNF-, IL-6, and IL-1, which lead to the accumulation of neutrophils at inflammatory sites. [5,6] In the current experiment, the sections obtained from the control and RIVA-treated groups revealed the gastric mucosa with no pathological changes. IND showed sloughed surface epithelium, vacuolated, and pyknotic cells.…”

“…Similarly, Abdelzaher et al [5] stated that IND administration increased UI, gastric acidity, and pepsin levels with decreased mucin. In addition, Naito et al [33] demonstrated that IND reduced with a protective function.…”

“…The current results proved that IND significantly increased UI, gastric acidity, and pepsin levels and suppressed mucin levels. Similarly, Abdelzaher et al [ 5 ] stated that IND administration increased UI, gastric acidity, and pepsin levels with decreased mucin. In addition, Naito et al [ 33 ] demonstrated that IND reduced mucin production, resulting in hydrogen ion back diffusion and lowering the mucosal membrane's protective ability against physical injury.…”

“…Because they disrupt gastroprotective factors, NSAIDs, particularly indomethacin (IND), are the most common cause of gastric lesion and ulceration. [ 5,6 ]…”

“…Because they disrupt gastroprotective factors, NSAIDs, particularly indomethacin (IND), are the most common cause of gastric lesion and ulceration. [5,6] Increased reactive radical production causes oxidative damage and inflammation of the stomach mucosa, leading to gastric lesions. [7] Free radicals oxidize mucosal barrier lipids and proteins, stimulate macrophages, and promote inflammatory cytokine production.…”