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Abstract

We previously reported that the gastric mucosa emits fluorescence of porphyrins at the onset of gastric lesions induced by hemorrhagic shock. In this study, we investigated whether the fluorescent substance concerns with the gastric mucosal injuries induced by diflofenac, a nonsteroidal antiinflammatory drug (NSAID). In the gastric mucosa treated with diclofenac, lesions were generated and myeloperoxidase activity increased. Diclofenac administration also increased thiobarbituric acid-reactive substances, a index of tissue peroxidation. After diclofenac treatment, the gastric mucosal fluorescence intensities rose. HPLC analysis demonstrated that the fluorescent substances were mesoporphyrin and protoporphyrin, which were the same as found in hemorrhagic shock. Pretreatment of the tissue with radical scavenging substances, catalase and troxipide, restrained the increase of mucosal fluorescence intensity, tissue peroxidation, and lesion formation. These findings indicate that diclofenac treatment induced the generation of porphyrins as well as tissue peroxidation in gastric mucosal tissue. This study suggests that autofluorescence observation is a useful tool to identify diclofenac-induced gastric injury.

A Molecular Biophysical Approach to Diclofenac Topical Gastrointestinal Damage

“…In summary, the DCF interactions with GI phospholipid model systems and IMM models demonstrated in this work provide a novel molecular and biophysical perspective to explain the reported topical harmful actions of DCF that could not be solely explained as resultant from COX inhibition. Although several interesting and important studies have used animal and cellular models to understand GI and mitochondrial toxicity of DCF [ 2 , 5 , 18 , 19 , 36 , 37 , 48 , 56 , 75 ], the use of lipid models avoids the complexity of biological systems while providing a basis for evaluating the structural and biophysical changes on lipid bilayers that are relevant for the functionality of native membranes. Our work was carefully planned regarding the lipid systems used, as well as the conditions of study, to provide a pertinent model for the lipid environment encountered by the drug in the biological milieu.…”

“…Diclofenac (sodium 2-[2-(2,6-dichloroaniline)phenyl]acetate) (DCF) is a non-steroidal anti-inflammatory drug (NSAID) generally used clinically, having an estimated global annual consumption of about 940 tons, including for human and veterinary purposes [ 1 ]. Despite its vast clinical use, DCF presents typical NSAID-related adverse effects of which gastrointestinal (GI) complications (e.g., GI bleeding and gastric ulceration) are the most relevant [ 2 , 3 , 4 , 5 ]. These GI effects have been considered to result mainly from the inhibition of cyclooxygenase (COX) enzyme, causing a decrease of prostaglandins that exert a strong protective effect on gastric mucosa, a mechanism known as prostaglandin hypothesis [ 6 ].…”

Therapeutic Effects of Hydrogel Formulations Incorporating Troxipide Nanoparticles on Oral Mucositis in Hamsters

“…Troxipide (TRO), also known as 3,4,5-trimethoxy-N-3-piperidinyl, inhibits oxidative stress and neutrophil-mediated inflammation, [5][6][7][8][9] along with enhancing cytoprotective prostaglandins secretion. 10 Due to these properties, TRO is used to treat gastroesophageal reflux disease, and its mechanism may enhance the treatment of severe OM.…”

Metabolites profiling and pharmacokinetics of troxipide and its pharmacodynamics in rats with gastric ulcer

“…It is used to alleviate gastric mucosal lesions (erosion, hemorrhage, redness, and edema) in the acute gastritis and acute exacerbation stages of chronic gastritis. Furthermore, troxipide can inhibit neutrophil-mediated inflammation and oxidative stress to increase gastric mucus secretion, increase the contents of mucopolysaccharide and prostaglandin E2 and enhance the positive effect of the gastric mucosa on barrier function 26 – 28 . And, the troxipide is soluble only at acidic pH and is mainly absorbed from the stomach 29 .…”