Tetramethylpyrazine ameliorates indomethacin-induced gastric ulcer in rats: Impact on oxidative, inflammatory, and angiogenic machineries

Abstract

Available antiulcer medications reveal partial efficacy and numerous adverse reactions. Tetramethylpyrazine (TMP) was known for its potential antioxidant, anti-inflammatory and angiogenic properties. The aim of current study was to investigate the potential gastroprotective effect of TMP against indomethacin-induced gastric ulcer in rats with possible underlying mechanisms. TMP was tested at 3 doses (15, 30 & 60 mg/kg/d po) three days before indomethacin challenge (25 mg/kg ip). Gastric tissue was evaluated morphologically and histopathologically. Oxidative statuses were assessed via glutathione content (GSH), malondialdhyde (MDA) and catalase (CAT) activity, while TNFα and IL-6 were measured as inflammatory mediators. Gastric PGE2 was investigated in addition to vascular endothelial growth factor (VEGF). TMP was effective (at 30 and 60 mg/kg/d) in promoting mucus secretion and preventing histopathologic changes induced by indomethacin. Mechanistically, TMP significantly enhanced GSH content and CAT activity while reducing lipid peroxidation as expressed by MDA concentration. Moreover, TMP effectively reduced TNFα, IL-6 and intracellular adhesion molecule (ICAM-1) concentrations. On the other hand, TMP enhanced both COX-1 and PGE2 and encouraged angiogenesis via increasing VEGF expression. In conclusion, TMP possesses a protective effect against indomethacin-induced gastric ulcer. This could be explained – at least partly – by its antioxidant, anti-inflammatory and angiogenic effects.

Defensive potential and deleterious impact of turmeric ( Curcuma longa ) L rhizome powder supplemented diet on antioxidant status of indomethacin‐induced ulcerated wistar rats

“…In this study, it was also observed that Aminotransferases in ALT and AST activities were significantly reduced in ulcerated group and this could ultimately affect the concentration of glutamate available for GSH synthesis which impact could be responsible for the reduced concentration of GSH in this ulcerated group of rats. These results are in agreement with results of some previous studies which reported that indomethacin plays a significant role in production of ROS and linked with damage of some organs such as liver and kidney (Alkreathy et al., 2020). Moreover, this study is in agreement with past studies which presented that there were certain cytotoxic activities of turmeric rhizome powder and that, high concentrations of curcumin in culture of rat hepatocytes induced LDH‐leakage and depletion of glutathione (Pannangpetch et al., 2000).…”

“…When an individual is exposed to increased levels of xenobiotics, more glutathione is employed for conjugation making it less available to act as an antioxidant. GSH has been reported to possess ability to stop tissue injury by neutralizing ROS (Alkreathy et al., 2020). Significant reduction in the concentration of kidney, cardiac and gastric (but insignificant in gastric 10%) GSH with reduced concentration of hepatic GSH observed in NC, 10% TRP supplemented diet groups when compared with CTL (Figure 2c) in this study could be an indication that large amount of GSH was used in maintaining redox balance by the liver in detoxifying the toxicity induced by indomethacin electrophile ROs.…”

“…This is consistent with existing results which suggested that protective mechanism may provide by curcumin against lipid peroxidation and oxidative stress (Wang et al, 2015). This is indicative of the dietary potential of Curcuma longa or curcumin to initiate the biosynthesis of antioxidant enzymes, as well as to decrease indomethacin‐ induced oxidative injury (Alkreathy et al., 2020; Yarru et al., 2009).…”

“…Many research studies have described the cause of oxidative stress as an imbalance between the production of reactive oxygen and a biological system’s capability to freely detoxify the reactive intermediates, which ultimately results in deterioration of oxidative lipid, protein, and DNA (Alkreathy et al., 2020; Nancy et al., 2018; Yadav et al., 2016). Oxidative stress is involved in pathology of many diseases, such as, heart failure, ulcerative and inflammatory lesions of the gastrointestinal tract, Parkinson’s disease atherosclerosis, chronic fatigue syndrome and myocardial infarction, in humans.…”

Optimized Self-Nanoemulsifying Delivery System Based on Plant-Derived Oil Augments Alpha-Lipoic Acid Protective Effects Against Experimentally Induced Gastric Lesions

“… 4 Based on several studies, the pathogenesis of IND-induced gastric ulcers include inhibition of protective prostaglandin E2 (PGE2) generation, excess production of inflammatory cytokines such as tumor necrosis tumor factor alpha (TNF-α), increased inducible nitric oxide synthase mediated nitric oxide production as well as augmented formation of reactive oxygen species (ROS). 5 - 7 ROS production interferes with the antioxidant enzyme activities and causes lipid peroxidation that is associated with mucosal damage. 8 To date, numerous antiulcer treatment options are available; however, further search is needed for less toxic, efficacious, and inexpensive antiulcerogenic drugs.…”