Metformin prevents hormonal and metabolic disturbances and 1,2-dimethylhydrazine-induced colon carcinogenesis in non-diabetic rats

Abstract

Effects of two doses of the anti-diabetic drug, metformin (MF), on hormonal and metabolic levels of serum of non-diabetic male Wistar rats with 1,2-dimethylhydrazine (DMH)-induced colon tumor adenocarcinomas were studied. Carcinogenesis in the animals was also observed. Rats with DMH-induced colon adenocarcinomas had elevated levels of serum glucose, insulin, insulin-like growth factor-1, total cholesterol, triglycerides, catalase, malonic dialdehyde, glycated hemoglobin, aspartate aminotransferase, and alanine aminotransferase and decreased hemoglobin. Treatment with two doses of MF normalized majority of these changes in DMH-treated rats, whereas the drug was ineffective in rats without DMH treatment. The only exception was the decreased triglyceride levels in MF-treated rats. A 100 mg/kg dose of MF increased DMH-induced exophytic colon carcinomas and decreased endophytic tumors compared with untreated rats. Moreover, both MF doses increased DMH-induced and highly differentiated tumors and decreased the invasiveness of colon carcinomas compared with rats provided with DMH and water. Therefore, effects of MF on metabolic homeostasis are critical for preventing colon cancer.

Keywords: 1,2-dimethylhydrazine; Colon cancer; metformin; prevention; rat.

1

Effect of 1,2-dimethylhydrazine (DMH) and metformin on hormonal and metabolic parameters in the serum male Wistar rats. (A) glucose. (B) Insulin. (C) IGF-1. (D) Total cholesterol. (E) Triglycerides. (F) Cu, Zn-superoxide dismutase. (G) Catalase. (H) Malonic dialdehyde. (I) Hemoglobin. (J) Glycated hemoglobin. (K) Alaninaminetransferase. (L) Aspartataminetransferase. (M) VEGF. Data presented as mean±SEM,n=6–15 per group.P≤0.05. a: DMHvs. control; b: DMH+MFvs. DMH. Rats bearing DMH-induced colon adenocarcinomas have elevated serum level of glucose, insulin, IGF-1, total cholesterol, triglycerides, catalase, malonic dialdehyde, glycated hemoglobin, AST, ALT and decreased level of hemoglobin. Treatment with MF in both doses normalized majority of these changes in DMH-treated group of rats, whereas failed to modify them in rats not treated with DMH. Only exception was decreased level of triglycerides in MF-treated rats (Figure 1E,P<0.05).

2

Effect of metformin on some parameters of 1,2-dimethylhydrazine-induced colon carcinogenesis in male Wistar rats. Data presented as mean±SEM,n=7–9 per group. *Р<0.01; §P<0.05vs. DMH group. Treatment with MF in dose 100 mg/kg increased relative number of induced with DMH exophytic colon carcinomas and decreased number of endophytic tumors. Both doses of MF increased relative number of DMH-induced highly differentiated tumors and decreased invasiveness of colon carcinomas as compare with group given DMH with water.

3

Microphotographs of 1,2-dimethylhydrazine-induced colon adenocarcinomas. (A) Highly differentiated adenocarcinoma. (B) Moderately differentiated adenocarcinoma. (C) Low differentiated adenocarcinoma (H&E stainning, 70×).