Dehydroepiandrosterone intake protects against 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in the obese Zucker rat model

Abstract

Abstract. Obesity has been epidemic in the US for over two decades; almost 65% of adults in the US are overweight. Obesity has been linked with the risk of development of various cancers, including breast cancer. Dehydroepiandrosterone (DHEA) is an over-the-counter dietary supplement used as an immunomodulating, anti-depressant, anti-aging, anti-cardiovascular disease, and anti-cancer agent and antiobesity supplement. The objectives of this study were to investigate the long-term effects of obesity and DHEA treatment on body weight gain and on 7,12-dimethylbenz(a)-anthracene (DMBA)-induced mammary tumor development. Forty-three six-week-old obese female Zucker rats were used. Rats were randomly assigned and had ad libitum access to water and a diet of either chow (2016) as a control diet or chow with the addition of DHEA at a concentration of 6 g/kg of chow as a DHEA diet. All rats were orally gavaged at age 50 days with 65 mg DMBA/kg body weight. Rats were weighed and palpated twice weekly for detection of mammary tumors and sacrificed 155 days post-DMBA treatment. Obese rats fed the DHEA diet gained significantly less weight than obese control diet rats (P<0.001). At the end of the experiment, 55% of the control diet group developed mammary tumors, while no tumors were detected in the DHEA diet group (P<0.001). Our results suggest that DHEA treatment can reduce body weight gain and protects against DMBA-induced mammary tumor development in the obese Zucker rat model.

Dehydroepiandrosterone (DHEA) Feeding Protects Liver Steatosis in Obese Breast Cancer Rat Model

“…The current results are additional new data from a previously reported study [19]. In the present study, we found that DHEA-fed rats had significantly lower liver weights and steatosis scores than control rats ( p < 0.001).…”

“…Previously, we reported that DHEA treatment can protect against mammary tumor development [19]. We reported that while only 55% of the obese control rats developed mammary tumors, there were no mammary tumors found in the DHEA-fed rats ( p < 0.001).…”

“…Previously, we have shown that DHEA treatment can protect against 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer development [19], but the effects of DHEA on liver steatosis in an obese breast cancer model are unknown. We hypothesized that obesity will increase liver steatosis and DHEA treatment will protect against liver steatosis by reducing body weight gain and modulating serum IGF-1 and IGFBP-3 levels in breast cancer model.…”

Triticale Bran Alkylresorcinols Enhance Resistance to Oxidative Stress in Mice Fed a High-Fat Diet

“…These results were expected since a high-fat diet is often correlated with increasing levels of ROS, leading to oxidative stress [24]. Overall, liver and heart tissues from HF-TB and HF-AR mice had significantly higher GSH levels and significantly lower ratios of GSSG/GSH ( p > 0.05) in comparison to mice fed the high-fat diet alone (Figure 7).…”

Pharmacology and immune modulating properties of 5-androstene-3β,7β,17β-triol, a DHEA metabolite in the human metabolome

“…In humans age-related declines in plasma DHEA coincide with a heightened pro-inflammatory status [2,3]. DHEA has activity in certain in vitro systems [4], and is remarkably effective as a chemoprotectant and anti-inflammatory agent in rodent models [4][5][6][7][8][9]. Published activities in rodent models include general anti-inflammatory effects [10], reversal of the aging phenotype [11], maintenance of bone mineral density [12], and enhanced immune [13][14][15], cognitive [16] and metabolic [17] functions.…”