Effects of cyclooxygenase-2 (COX-2) selective and nitric oxide (NO)-releasing NSAIDs on mucosal ulcerogenic and healing responses of the stomach

Ukawa, Hideki; Konaka, Akira; Hirata, Tetsuya; Takeuchi, Koji

doi:10.1016/s0021-5198(19)40602-1

Cited by 3 publications

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“…One of the important side effects of ASA is the development of gastric ulceration and erosion [45]. As consequence, its modifications with a lessened, or absent, effect are in development.…”

Section: Discussionmentioning

confidence: 99%

A new derivative of acetylsalicylic acid and carnosine: synthesis, physical and chemical properties, biological activity

et al. 2020

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Purpose The aim of this study was to create and assess biological activity of a new compound based on carnosine and acetylsalicylic acid (ASA) that will comprise antioxidant effect with antiplatelet activity, while simultaneously preventing side effects on the gastrointestinal tract. Methods Salicyl-carnosine (SC) was synthesized by condensation of ASA and carnosine. Antioxidant activity was determined by spectrophotometric and chemiluminescence methods. Antiplatelet activity was carried out by the light transmissionaggregometry method using the inductor ADP. Chronic gastric ulcer in rats was modeled using glacial acetic acid. Results Using SOD-like activity, iron-induced chemiluminescence, BaSO4-activated respiratory burst, and evaluation of red blood cell structure stabilization during oxidative damage induced by sodium hypochlorite, it was shown that SC possesses antioxidant activity analogous, or better, than that of carnosine. Antiplatelet activity of SC was evaluated in the blood of healthy individuals, and was also shown to be comparable to, or exceeding that of ASA. Also SC demonstrates high resistance to hydrolysis by tissue and serum carnosinases. Most importantly, it was shown that SC has protected the gastric mucosa against the formation of stomach ulcerative lesions and promoted their epithelization, therefore overcoming the undesirable inherent side effects of ASA. Conclusions SC preserves pharmacologically significant properties of ASA and carnosine while retaining an anti-ulcer activity and resistance to the carnosinase hydrolysis at the same time. These properties are particularly promising for the potential development of new anti-inflammatory and antithrombotic drugs. KeywordsCarnosine . Acetylsalicylic acid . Salicylic acid . Antioxidant . Antiplatelet action . Gastrointestinal ulcer Abbreviations ASA acetylsalicylic acid CL chemiluminescence COX cyclooxygenase HPLC high performance liquid chromatography HRMS high resolution mass spectrometry LP lipoproteins LPO lipid peroxidation NBT nitroblue tetrazolium NSAIDs non-steroidal anti-inflammatory drugs

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Section: Discussionmentioning

confidence: 99%

A new derivative of acetylsalicylic acid and carnosine: synthesis, physical and chemical properties, biological activity

et al. 2020

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“…On the other hand, it is known that the healing of gastric ulcers is delayed by repeated administration of NSAIDs, in association with the suppression of mucosal PGE 2 generation, and this property of NSAIDs is shared by selective COX‐2 inhibitors (Ukawa et al, ; Hatazawa et al, ). Indeed, COX‐2 mRNA and protein are strongly expressed in the ulcerated mouse stomach, with a parallel increase in mucosal PGE 2 production, suggesting an important role for COX‐2/PGE 2 in the healing of gastric ulcers (Mizuno et al, ).…”

Section: Commentarymentioning

confidence: 99%

Evaluation of Gastric Ulcerogenic and Healing Impairment Effects of Bisphosphonates: Adverse Gastric Reactions of Bisphosphonate

Takeuchi

Amagase

2012

CP Toxicology

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Bisphosphonates (BPPs) were developed as antiresorptive drugs capable of treating diseases related to bone remodeling; however, they have untoward effects including ulceration in the upper gastrointestinal tract and worsen the healing-impairment action of nonsteroidal anti-inflammatory drugs, prescribed in patients with arthritis or osteoporosis. We produced ulcers in the antrum by administering BPPs to fasted rats, followed by refeeding, and confirmed their healing-impairment action on pre-existing gastric ulcers; the ulcerogenic effect is due to direct mucosal irritation and decrease in the mucosal anti-oxidative system, while the latter effect is due to dysregulation of growth factor expression, such as vascular endothelial growth factor and basic fibroblast growth factor, and angiogenesis in the ulcerated mucosa. In this article, we describe these two animal models for investigating BPP-related adverse reactions, including methods for the induction of antral ulcers and healing impairment of gastric ulcers, as well as measurement of pathogenic functional and biochemical changes.

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The role of COX-2 gene variants on the disease mechanism of inflammatory bowel disease in a Turkish population

İplik

Kahraman

Ertuğrul³

et al. 2018

Archives of Clinical and Experimental Medicine

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Aim: Inflammatory bowel disease has two major types: Crohn's disease and ulcerative colitis that occur in the gastrointestinal tract with unknown etiology. COX-2 has important role on carcinogenesis process including colon cancer supporting the tumor growth. COX-2 was also known due to its ability to change homeostasis on colonic mucosa in inflammatory cells on patients who have inflammatory bowel disease. In this study, we have aimed to find a linkage between inflammatory bowel disease and COX-2 in a Turkish population. Methods:A total of 106 patients,42 with Crohn's disease and 64 with ulcerative colitis and 121 healthy control subjects were included the study. Gene variants of COX-2-765G→C and COX-2-1195A→G were analyzed by polymerase chain reaction and restriction fragment length polymorphism techniques. Results: The results demonstrated that COX-2-1195A→G gene variants AA carriers were statistically found in high level on patients with both ulcerative colitis (p=0.001) and Crohn's disease (p=0.008). In contrast, AG genotype and G carriers were statistically found higher in control group (Crohn's disease, p=0.005 for AG and p= 0.008 for G; ulcerative colitis, p=0.001 for AG and p=0.001 for G). Conclusion: In this research, we have observed important and questionable results between inflammatory bowel disease and COX-2, especially COX-2-1195A→G gene variants AA carriers in a Turkish population. Researches need to focus on their local roles on inflammatory bowel disease pathogenesis with large sample size.

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Effects of cyclooxygenase-2 (COX-2) selective and nitric oxide (NO)-releasing NSAIDs on mucosal ulcerogenic and healing responses of the stomach

Cited by 3 publications

References 0 publications

A new derivative of acetylsalicylic acid and carnosine: synthesis, physical and chemical properties, biological activity

A new derivative of acetylsalicylic acid and carnosine: synthesis, physical and chemical properties, biological activity

Evaluation of Gastric Ulcerogenic and Healing Impairment Effects of Bisphosphonates: Adverse Gastric Reactions of Bisphosphonate

The role of COX-2 gene variants on the disease mechanism of inflammatory bowel disease in a Turkish population

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