Hemin protects against cell stress induced by estrogen and progesterone in rat mammary glands via modulation of Nrf2/HO-1 and NF-κB pathways.

Mammary gland hyperplasia is one of the risk factors for breast cancer. Till date, there is no study that has addressed the effect of hemin in this condition. Thus, this study was designed to evaluate the effect of the heme oxygenase 1 (HO-1) inducer (hemin) and its inhibitor (zinc protoporphyrin-IX) (ZnPP-IX) on mammary gland hyperplasia (MGH) induced by estrogen and progesterone in adult albino rats. Forty adult female albino rats were divided into the control group, MGH group, MGH + Hemin group, and MGH + Hemin + ZnPP-IX group. Serum levels of estradiol and progesterone were measured. Breast tissues were taken for estimation of oxidative, inflammatory, and apoptotic markers. Mammary gland histology was performed, and expression of Ki-67, Beclin, and P53 in breast tissue was also measured. Estrogen and progesterone administration induced hyperplasia of cells lining the ducts of the breast tissues associated with increased diameter and height of the nipples as well as increased oxidative stress markers, inflammatory markers, antiapoptotic markers, and cell autophagy. Hemin administration during induction of MGH can reverse all the affected parameters. Then, these effects were abolished by ZnPP-IX administration. We concluded that hemin administration can antagonize the cell stress induced by estrogen and progesterone and protect against the development of mammary gland hyperplasia via modulation of Nrf2/HO-1 and NF-κB pathways.