Estrogen and/or Progesterone Effects on HepG2 Human Cell Lines; Oxidant or Antioxidant?

Although much is known about estrogen and progesterone, their toxicity or protective effects on hepatocytes are yet to be fully understood. This study investigated the probable oxidant or antioxidant effects of estrogen and progesterone on HepG2 cell line in the presence or absence of H2O2. HepG2 cells were cultured with two concentrations of estrogen and progesterone (10PM and 1μM) and H2O2 (50 and 200 μM) separately, and in combination, for 24 hours. The effects of selected doses after MTT assay on: 1) cellular integrity, 2) GR and GPx activity, 3) cellular levels of GSH and 4) ALT and AST activities were assessed.  MTT assay showed toxic effect of 200 µM H2O2 on the cells. According to MTT results, 10nM and 1 µM doses of estrogen and progesterone and 1µM of each in combination, in the presence of 50 µM H2O2 were selected for the rest of the experiments. Incubation of the cells with H2O2 caused a remarkable decrease in GPx and GR activities as well as GSH level, and an increase in ALT and AST levels. However, treatment with estrogen attenuated further changes and estrogen in combination with progesterone led to a more pronounced amelioration of H2O2-induced toxicity.   Our results demonstrated that while high level of oxidative stress is severely cytotoxic, estrogen and progesterone might significantly improve the antioxidant defense within hepatocytes which undergo a low-intensity oxidative exposure.