Effect of Aminosteroid U74389G in a Model of Inflammatory Bowel Disease in Rats

Abstract

Summary Lazaroid U-74389G is a synthetic 21-aminosteroid with free radical-scavenging and anti-inflammatory effects. This study was designed to evaluate the anti-inflammatory activity of U-74389G on experimental 2,4-dinitrobenzene sulfonic acid hydrate (DNBS)-induced colitis in Wistar rats. Five experimental groups were formed: a sham control group, a control group, treated with 0.25 ml of 50% ethanol intrarectally (n=8), a group treated with DNBS (30 mg in 0.25 ml of 50% ethanol administered intrarectally, (n=8), a group treated with DNBS and U-74389G at a daily dose of 15 mg/kg i.p. (n=8), and a group treated with DNBS and sulfasalazine, orally, at a dose of 300 mg/kg. During the experiment, the bodyweight of the rats, food intake, stool consistency, and presence of blood in the stool were recorded as markers of clinical condition. On day 6, colonic tissues were excised and scored for macroscopic and histological damage. Blood samples were taken to measure levels of cytokines by ELISA methods. DNBS decreased significantly body weight (from 237.00±2.52 g to 212.50±6.25 g, p=0.04). The rats treated with U-74389G showed greater food intake and weight gain. U-74389G reduced ulceration index: the U-74389G score was 1.25±0.25, and the DNBS score –3.87±0.61; p<0.05. All other macroscopic parametersassessed were significantly improved in rats treated with U-74389G. The levels of inflammatory cytokines IL-1, IL-6, and TNF-α, were significantly lower than those of the DNBS group, while U-74389G significantly elevated the level of anti-inflammatory IL-10. These findings indicate that U-74389G significantly inhibits colonic inflammatory damages in a rat model of inflammatory bowel disease.