Suppressive Effect of Irsogladine Maleate on Diethylnitrosamine‐initiated and Phenobarbital‐promoted Hepatocarcinogenesis in Male F344 Rats

Abstract

Modifying effects of irsogladine maleate (IRG) on diethylnitrosamine (DEN)-induced hepatocarcinogenesis were examined in male F344 rats. Six-week-old rats were divided into 8 groups. Groups 1 through 4 were given a single i.p. injection of DEN (200 mg/kg body weight) at the start of the experiment, whereas groups 5 through 8 received a single i.p. injection of saline as the vehicle treatment. Groups 1 and 8 were kept on the basal diet and distilled water throughout the experiment (36 weeks). Groups 2 and 7 were exposed to 500 ppm phenobarbital (PB) in the drinking water, starting one week after the carcinogen or vehicle treatment. Groups 3 and 5 were fed the diet mixed with 125 ppm IRG from one week after DEN or vehicle treatment. Groups 4 and 6 were given 125 ppm IRG-containing diet and drinking water with 500 ppm PB after the carcinogen or vehicle treatment. Liver neoplasms developed in groups 1 (1/15 rats, 7%) and 2 (14/14 rats, 100%). However, no liver tumors were found in rats of groups 3 through 8. Incidence and average number of liver neoplasms in group 4 (0/14 rats, 0%) were less than those in group 2 (P< < < <0.0001).The number of glutathione S-transferase placental form (GST-P)-positive liver cell foci in group 3 or 4 was significantly smaller than that in the appropriate control (P< < < <0.01, P< < < <0.001, respectively).The average and unit areas of these foci in group 4 were also significantly smaller than those in group 2 (P< < < <0.001, P< < < <0.05, respectively). These results suggest that IRG could be a chemopreventive agent for rat liver carcinogenesis.

Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in Apc-mutant mice

“…Twenty-five or 100 ppm irsogladine maleate in the diet for 25 weeks reduced the average numbers of digestive tract neoplasms up to 61% of the untreated group value. In addition, another report described the suppressive effects of irsogladine maleate on diethylnitrosamine (DEN)-initiated and phenobarbital-promoted hepatocarcinogenesis in male F344 rats [ 11 ]. Irsogladine maleate in the diet at 125 ppm for 35 weeks did not allow the development of liver neoplasms (incidence, 0/14 rats).…”

Inhibition of Breast Cancer Regrowth and Pulmonary Metastasis in Nude Mice by Anti-gastric Ulcer Agent, Irsogladine

“…Experimentally, irsogladine has been shown to inhibit angiogenesis [10,11] and carcinogenesis [17,18].…”

Impact of naringenin on glycoprotein levels in N-methyl-N′-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats

“…Fruits, vegetables and herbal beverages with diverse pharmacological properties have been found to possess a myriad of cancer prevention potentials [13][14][15][16][17]. It is widely believed that carcinogenesis can effectively be kept at bay by the ingestion of certain plant-derived foods rich in flavonoids [18][19][20][21].…”