The Hepatoprotective mechanisms of 17β-estradiol after traumatic brain injury in male rats: Classical and non-classical estrogen receptors

Protective effects of estrogen (E2) on traumatic brain injury (TBI) have been determined. In this study, the hepatoprotective effects of E2 after TBI through its receptors and oxidative stress regulation have been evaluated. Diffuse TBI induced by the Marmarou method in male rats. G15, PHTPP, MPP, and ICI182–780 as selective antagonists of E2 were injected before TBI. The results indicated that TBI induces a significant increase in liver enzymes [Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Glutamyl transferase (GGT)], and oxidants levels [Malondialdehyde (MDA), Nitric oxide (NO)] and decreases in antioxidant biomarkers [Glutathione peroxidase (GPx) and Superoxide dismutase (SOD)] in the brain and liver, and plasma. We also found that E2 significantly preserved levels of these biomarkers and enzymatic activity. All antagonists inhibited the effects of E2 on increasing SOD and GPx. Also, the effects of E2 on brain MDA levels were inhibited by all antagonists, but in the liver, only ICI + G15 + E2 + TBI group was affected. The impacts of E2 on brain and liver and plasma NO levels were inhibited by all antagonists. The current findings demonstrated that E2 probably improved liver injury after TBI by modulating oxidative stress. Also, both classic (ERβ, ERα) and non-classic [G protein-coupled estrogen receptor (GPER)] receptors are affected in the protective effects of E2. [Display omitted] •Traumatic brain injury (TBI), in addition to brain injury, can lead to hepatic damage in rats.•The increase in liver enzymes [ALP, AST, ALT, GGT], apoptosis, and oxidative stress alleviated by E2 after TBI.•In the liver, the hepatoprotective effects of estrogen are exerted through the ERα rather than ERβ and GPER.•In the brain, neuroprotective effects of E2 via the ERβ more than the ERα and GPER after TBI.•In the plasma, both classic and non-classic E2 receptors were involved in the regulation of GPx and NO after TBI.