Effect of long-term metronidazole (MTZ) therapy on experimental colon cancer in rats

Abstract

Current reports suggest a beneficial effect of long-term metronidazole (MTZ) therapy in Crohn's disease. Since Crohn's disease is associated with a higher risk of bowel cancer and long-term MTZ has been shown to have a tumorigenic potential in rodents and a cocarcinogenic effect in experimental colon cancer, more studies are required to explore this area. Eighty-one rats were divided into four groups. Group A served as a control, groups B and C were given MTZ in their food (50 mg/kg/day). In groups C and D, a 3-cm colonic segment was isolated and brought out as a blind loop fistula. All animals received 20 weekly sc doses of 1,2-dimethylhydrazine (DMH) and were killed 25 weeks after the first injection. The mean number of colon tumors per animal (±SEM) in MTZ groups B (1.65 ± 0.29) and C (2.57 ± 0.38) were higher than A (1.44 ± 0.3) and D (1.18 ± 0.21), but the increase was only significant for group C over groups A and D ( P < 0.05) and group B ( P = 0.06). The mean number of tumors per animal in the isolated loop of group C (0.95 ± 0.28) was similar to group D (0.68 ± 0.16) P = 0.41, but the mean number of tumors in the functioning colon of group C (1.62 ± 0.25) was higher than group D (0.5 ± 0.12) P < 0.001. These findings suggest that (1) long-term MTZ increased the number of colon tumors per rat in the DMH model but a statistical significance ( P < 0.05) was only noted in the MTZ and surgery group. (2) Surgery alone did not increase the number of tumors. (3) This effect of MTZ is dependent on the presence of the fecal stream, since there was no significant difference between the number of tumors in the empty loops of MTZ and non-MTZ groups.