Pathological effects caused by chronic treatment of rainbow trout with indomethacin

The purpose of this study was to determine adequate dose ranges and to test for side effects associated with chronic treatment of fish with indomethacin. Rainbow trout Oncorhynchus mykiss were orally treated with indomethacin at various nominal concentrations: a negative control (0 mg/kg) and low (5 mg/kg), medium (10 mg/kg), and high doses (15 mg/kg) daily for 30 d. A dose-associated mortality was observed, as cumulative mortality was 3, 13, and 33%, respectively, in the three indomethacin dose groups. No lesions were observed grossly or with histopathology in the control and low-dose treatment groups. Gross lesions were observed in the medium- and high-dose groups, including skin ulcers, abdominal distension, and necrosis of abdominal wall muscle. Histopathology of fish in the medium- and high-dosage groups revealed severe granulomatous peritonitis in which a large number of foreign body type giant cells were present around proteinaceous and plant material. The inflammatory response spread from the peritoneum through the somatic muscle to the epidermis, causing lesions within all layers of the skin. A large number of bacteria were noted within the peritonitis, observed both intracellularly and in large aggregates extracellularly. Perforations occurred within the anterior intestine, and the thick muscularis layer was replaced with inflammatory tissue. The present investigation shows that chronic indomethacin treatment produces gastrointestinal side effects in rainbow trout similar to those seen in mammals.