Oral misoprostol does not protect the kidneys from diclofenac induced toxicity: data from an unilateral ureteral obstructive rat model

Abstract

OBJECTIVE: Ureteral obstruction leads to permanent changes in the structure of the kidney by several mechanisms. In this study, it was hypothesized that there would be a protective effect of misoprostol against diclofenac in rats with unilateral ureteral obstruction (UUO). MATERIALS AND METHODS: Twenty-two female rats were randomized into 5 groups of 4 and 2 rats for the control group. The right ureter was sutured. The rats were grouped as control, contrast agent, contrast agent +N-acetylcysteine (NAC), diclofenac and diclofenac + misoprostol groups. Radiographic contrast agent was given iv on the 3rd day and other agents were administered orally for 1 week. The rats were sacrified after 1 week and histopathological and biochemical oxidative stress markers were evaluated. RESULTS: The contrast agent and NAC group had lower rates of hemorrhage, inflammation, obstructive dilatation and fatty degeneration compared to the contrast agent only group (p < 0.05). No differences were seen in the normal kidneys. Between all the groups, there was no difference for tubule epithelium damage (p > 0.05). The contrast agent and NAC group had higher rates of antioxidant SH level compared to the contrast agent only group (p < 0.05) and lower rates of oxidative end product carbonyl groups (p < 0.05). For normal kidneys no difference was seen. No statistical difference was seen in MDA levels (p > 0.05). Statistically no difference was seen between the diclofenac group and the diclofenac and misoprostol group neither pathologically nor chemically (p > 0.05). CONCLUSIONS: These results showed that NAC is protective against radiographic contrast agent toxicity when given before and after administration in obstructed kidneys as in previous data. Misoprostol was not observed to have any protective effect against diclofenac in obstructed kidneys.