Does oestradiol treatment alleviate obesity-induced oxidative stress in the male liver?

Abstract

The liver is an organ in which many oxidative processes occur and represents an important target of oxidative stress (OxS). Under physiological conditions of normal mitochondrial homeostasis, hepatocytes effectively remove reactive oxygen species (ROS) by enabling metabolic adaptations and through the antioxidant defence system mechanisms. However, obesity-induced lipid accumulation in the hepatocytes causes significantly elevated production of ROS, reduces oxidative capacity, and increases oxidative stress (OxS). In men, compared with premenopausal women, the development of insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in obesity are more prevalent, where oestradiol (E2), the most potent female sex steroid, is proposed as the main culprit. Exogenous oestradiol (E2) administration exerts beneficial effects on antioxidant properties, restores total plasma antioxidant capacity and decreases biomarkers of OxS in ovariectomized animal models. Thus, we hypothesized that E2 treatment in states of obesity could have beneficial effects againstOxS in the obese male's liver. We assumed that E2 could directly affect the level of OxS by increasing the level/activity of the AOS enzymes, particularly SOD1, SOD2, GPx, and CAT, in obese males' livers. In addition, we assumed that the level of malondialdehyde (MDA) and protein carbonyl content (PCC) in obese males' livers would be reduced after E2 treatment as a result of E2 inhibitory effect on lipid peroxidation and protein oxidation, respectively. To test our hypothesis, we used the liver of a high-fat (HF) diet-fed male Wistar rats as an animal model of obesity, treated with E2 intraperitoneally (40 μg/kg). Preliminary results from this study support our hypothesis that E2 increases liver protein expression of AOS enzymes: SOD1, GPx, and CAT, in control and HF male rats compared with their respective controls. The protein level of SOD2 and CAT activity was increased in HF treated with E2 compared with non-treated HF rats. Moreover, as we expected, E2 administration significantly decreased the MDA level in both E2-treated groups compared to their controls, while the PCC level was significantly decreased in HF treated group compared with untreated HF rats. In conclusion, the preliminary results we obtained in this study indicate that E2 administration can effectively inhibit the OxS-related processes in the liver in HF diet-induced obesity by increasing AOS enzymes levels and CAT activity, and also by decreasing levels of MDA and PCC. A consequence of our hypothesis is that treatment with E2 may be an innovative way to improve obesity-related liver disease prevention and healing.