LAUSR

5,10,15,20-Tetrakis (4-sulfonatophenyl) porphyrinato iron(III) chloride (FeTPPS) is a water-soluble analog of heme and widely employed as peroxynitrite scavenger in vivo. However, previous studies have showed that like heme, FeTPPS could also act as an effective pro-oxidant towards appreciable substrates in vitro in the presence of oxidant. The reason that FeTPPS did not show any pro-oxidative damage in previous studies when it was used as peroxynitrite decomposition catalyst in vivo, has not been studied. Herein, the effects of two main detoxification mechanisms of heme, i.e., serum albumin (SA) binding and heme oxygenase-1 (HO-1) induction, were examined on FeTPPS in vitro. Fluorescence quenching studies showed bovine serum albumin (BSA) could bind to FeTPPS with high affinity (Kb ~ 109 M-1). Molecular docking studies presented us the details of the binding site that is not a heme pocket. Furthermore, the intrinsic pro-oxidative activity of FeTPPS was found effectively inhibited by forming BSA-FeTPPS complex of low reactivity, which could be thought to protect against the potentially toxic effects of FeTPPS on blood components. In addition, this binding could protect FeTPPS against oxidative degradation. In albumin-free cell system, cell viability results indicated FeTPPS was innoxious to living cells and could protect cells against the oxidative impairment of H2O2 effectively rather than promoting damage. Using western blot, we illustrated that HO-1 expression could not be induced by FeTPPS, which suggested that HO-1 was not related to the protective capacity of FeTPPS. Our results provide a better understanding of FeTPPS and lead to a new guidance to its application.