Intestinal toxicity of ketoprofen-trometamol vs its enantiomers in rat. Role of oxidative stress

• Published in: Inflammation research 2000-11, Vol.49 (11), p.627-632
• Main Authors: de la Lastra, C A, Nieto, A, Motilva, V, Martín, M J, Herrerías, J M, Cabré, F, Mauleón, D
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - toxicity; Intestinal Diseases - chemically induced; Intestinal Diseases - enzymology; Intestinal Diseases - immunology; Intestinal Mucosa - drug effects; Intestinal Mucosa - enzymology; Ketoprofen - administration & dosage; Ketoprofen - toxicity; Male; Neutrophil Infiltration - drug effects; Oxidative Stress; Peroxidase - metabolism; Rats; Rats, Wistar; Stereoisomerism; Superoxide Dismutase - metabolism; Tromethamine - administration & dosage; Tromethamine - toxicity; Ulcer - chemically induced; Ulcer - enzymology; Ulcer - immunology; Xanthine Oxidase - metabolism
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s000110050640

Gastrointestinal damage and bleeding are the major side effects of non-steroidal anti-inflammatory drugs (NSAID), however the mechanisms of this ulcerogenic action are not fully understood. It has recently been proposed that neutrophil-and oxygen radical-dependent microvascular injuries may be important prime events that lead to mucosal injury. In addition, other factors like bile flow, intact bacterial flora or feeding conditions may contribute to the formation of lesions. Ketoprofen is a NSAID that exists as a pair of R(-) and S (+) enantiomers; like other 2-arylpropionic acids, its anti-inflammatory effects resides almost exclusively in the S (+) isomer. The present study was undertaken to explore the role of oxidative stress in the pathogenesis of intestinal injury induced by oral administration of racemic ketoprofen and its enantiomers given as their water soluble tromethamine salts. Evaluation of intestinal damage and activities of oxidative stress related enzymes such as myeloperoxidase (MPO), xanthine-oxidase (XO) and superoxide dismutase (SOD) were studied in an experimental animal model using refed rats. After the oral treatment followed by a refeeding period of 24 h, ketoprofen (100, 50, 25 mg/Kg b.w.) dose-dependently caused longitudinal ulcers on the mesenteric side of the middle and lower intestine lumen. The intestinal toxicity caused by S(+)-ketoprofen was significantly lower than the effect observed after racemate and R(-) enantiomer treatments (P