Amelioration of estrogen-induced endometrial hyperplasia in female rats by hemin via heme-oxygenase-1 expression, suppression of iNOS, p38MAPK and Ki67.

Although heme oxygenase-1 (HO-1) is part of an endogenous defense system implicated in the homeostatic response, its role in cell proliferation and tumor progression is still controversial. Endometrial hyperplasia (EH) is with high risk of endometrial cancer (EC). Therefore, we aimed to evaluate the effect of HO-1 inducer; hemin against EH. Thirty two adult female rats were included into four groups: control group; hemin group (25mg/kg; i.p. 3 times/week); estradiol valerate (EV) group (2 mg/kg/day, p.o.) and group received hemin plus EV. Sera were obtained for reduced glutathione (GSH) level. Uterine malondialdehyde (MDA), superoxide dismutase (SOD), total nitrite/nitrate (NOx) and interleukin-1β (IL-1β) levels were estimated. HO-1 and p38 Mitogen-activated protein kinase (p38MAPK) expressions were obtained in uterine tissue. Uterine histological and immunohistochemical assessment of iNOS and Ki-67 were also done. Results proved that upregulation of HO-1 expression in EV rats received hemin led to amelioration of EH which was confirmed with histological examination. This was associated with significant decrease in oxidative stress parameters, p38 MAPK expression and IL-1β level. Also, uterine iNOS and Ki67 expressions were markedly suppressed. In conclusion, upregulation of HO-1 expression via hemin has ameliorative effect against EH through its anti-oxidant, anti-inflammatory and anti-proliferative actions.