Selenium rescues orbital fibroblasts from cell death induced by hydrogen peroxide: another molecular basis for the effects of selenium in graves’ orbitopathy

Excerpt

In vivo and in vitro studies suggest that the anti-oxidant agent selenium can be used for the treatment of Graves’ disease (GD) and Graves’ orbitopathy (GO) [1‐3]. GO, the most common extrathyroidal manifestation of GD [4‐6], is due to an autoimmune reaction against orbital fibroadipose tissue, following which a number of effector mechanisms, including oxidative stress, are responsible for the pathological changes of the orbit [7]. Treatment with selenium is associated with an improvement of mild GO [2], and recently we reported that selenium exerts antioxidant actions in vitro, namely in orbital fibroblasts exposed to oxidative stress by incubation with hydrogen peroxide (H₂O₂) [3]. H₂O₂ was cytotoxic if used at concentrations ≥10 μM, but at 5 μM it elicited proliferation of fibroblasts and cytokine release [3]. The effects of H₂O₂ were counteracted by selenium, which also caused a reduced release of hyaluronic acid [3]. When performing the experiments of our previous study, we observed casually that selenium seemed to counteract also the cytotoxic action of H₂O₂. Hence, we conducted an additional study aimed at investigating whether selenium is actually capable of inhibiting H₂O₂-dependent cytotoxicity, as well as at comprehending the mechanisms underlying H₂O₂ cytotoxicity and selenium actions. …