Suppressive effect of irsogladine maleate on N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-initiated and glyoxal-promoted gastric carcinogenesis in rats

Abstract

The modifying effect of irsogladine maleate (IRG) on N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-initiated and glyoxal-promoted gastric carcinogenesis was examined in male Wistar rats. Six-week-old rats were divided into ten groups. Groups 1 through 6 were given MNNG (100 mg/l in drinking water) for 25 weeks from the start of the experiment, whereas groups 7 through 10 received distilled water in the initiation phase as the vehicle treatment. Groups 1 and 8 were kept on the basal diet and distilled water throughout the experiment (55 weeks). Groups 2-8 were given 0.5% glyoxal in the drinking water for 30 weeks from 26th week of the experiment. Group 3 was fed the diet mixed with 100 ppm IRG for 25 weeks from the start of experiment. Groups 4 and 8 were fed the diet mixed with 100 ppm IRG for 30 weeks from 26th week of experiment. Groups 5 and 9 or 6 were given 100 or 25 ppm IRG containing diet, respectively throughout the experiment. Group 10 was given the basal diet and distilled water as the vehicle treated control. Tumors of upper digestive tracts (stomach and duodenum) were developed in groups: 1 (12/17 rats, 71%), 2 (11/12 rats, 92%), 3 (9/16 rats, 56%), 4 (5/12 rats, 42%), 5 (6/15 rats, 40%) and 6 (7/12 rats, 58%). High dose of IRG in initiation and/or promotion phase significantly reduced the incidence of tumors of the upper digestive tracts. The average numbers of the digestive tracts neoplasms in groups 3,5 and 6 given glyoxal and IRG were less than those in group 2 which received only glyoxal. These results suggest that IRG could be a preventive agent against the occurrence of neoplasms of the upper digestive tract.