Metabolic Effects of Pioglitazone in Chemically-Induced Mammary Carcinogenesis in Rats

Abstract

In this paper, the effect of peroral antidiabetic pioglitazone, a thiazolidinedione derivate, on selected parameters of carbohydrate and lipid metabolism in N-methyl-N-nitrosourea-induced mammary carcinogenesis in female Sprague-Dawley rats was evaluated. Pioglitazone was administered in the diet at two concentrations (10 ppm and 100 ppm), the chemoprevention was initiated 12 days before carcinogenesis induction and lasted until the termination of the experiment. The experiment was terminated 17 weeks after carcinogenesis induction, selected organs and tissues were removed and weighed and basic metabolic and hormonal parameters were determined. Pioglitazone increased glycemia (without exceeding normal values) and glycogen concentration in both liver and heart muscle without altering insulinemia and increased triacylglycerol concentration in liver, these changes were more prominent in group with higher dose. Pioglitazone also reduced corticosterone serum concentration and attenuated lipid peroxidation. Pioglitazone and other glitazones may be useful in alleviation of unfavourable metabolic changes in cancer patients.

Rosiglitazone Shows Partial Oncostatic Effect in Rat Mammary Carcinogenesis

“…However, according to some authors, the decreased INS concentrations are secondary to the decreased food intake and not the presence of a tumor per se [63,64]. In this work, lower ROS dose decreased glycaemia and insulinaemia but glycaemia values in all groups remained in the normal range, as they did in previous reports with metformin and pioglitazone administration, respectively [59,52]. No changes in serum INS after ROS administration were reported by Nunez et al [34] as well.…”

“…Serum cortisol increases in breast cancer patients, especially in those with weight loss [60], serum CTS increased in control animals (administered with NMU) in our previous reports too and chemoprevention (with metformin and pioglitazone, respectively) [59,52] decreased it. Surprisingly, in this work serum CTS was not changed after higher ROS dose and even rose after lower ROS dose, while metformin and particularly pioglitazone markedly decreased serum CTS [59,52]; this might contribute to lack of ROS antitumor efficacy as glucocorticoids can inhibit apoptosis in mammary epithelial cells [61,62].…”

“…Surprisingly, in this work serum CTS was not changed after higher ROS dose and even rose after lower ROS dose, while metformin and particularly pioglitazone markedly decreased serum CTS [59,52]; this might contribute to lack of ROS antitumor efficacy as glucocorticoids can inhibit apoptosis in mammary epithelial cells [61,62].…”

“…ROS administration had no effect on weight loss (and periovarial fat weight loss) in rats administered with carcinogen despite tendency to normalise food intake (at higher dose). Similarly, no effect on body weight gain was recoreded in the same experimental model using pioglitazone although higher pioglitazone dose (100 ppm in a diet) increased food intake and insignificantly periovarial fat weight too [52]. Asp et al [53] reported initial weight loss delay and adipose depletion attenuation in mice with cancer cachexia administered with ROS, which, however, did not persist, food intake eventually declined as well.…”

“…This was proved in our previous work with metformin [59] but not in this experiment, in NMU+ROS10 group, however, serum IGF-1 increased unexpectedly. Nunez et al [34] and Kocdor et al [35] found no changes in serum IGF-1 level after ROS administration and similarly, pioglitazone administration did not change serum IGF-1 level [52].…”