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 (K_b ~ 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.

5,10,15,20-四（4-磺酰基苯基）卟啉铁（III）氯化物（FeTPPS）是血红素的水溶性类似物，在体内广泛用作过氧亚硝酸盐清除剂。但是，先前的研究表明，FeTPPS像血红素一样，在存在氧化剂的情况下，还可以在体外对明显的底物起有效的促氧化剂作用。当FeTPPS用作体内过氧亚硝酸盐分解催化剂时，FeTPPS在先前的研究中未显示任何促氧化损伤的原因尚未得到研究。在本文中，研究了血红素的两种主要排毒机理，即血清白蛋白（SA）结合和血红素加氧酶-1（HO-1）诱导对FeTPPS的影响。。荧光猝灭研究表明牛血清白蛋白（BSA）可以结合FeTPPS以高亲和力（K _b  〜10 ⁹ 中号^-1）。分子对接研究向我们展示了不是血红素口袋的结合位点的细节。此外，发现形成低反应性的BSA-FeTPPS复合物可有效抑制FeTPPS的内在促氧化活性，认为这可以防止FeTPPS对血液成分的潜在毒性作用。另外，这种结合可以保护FeTPPS免于氧化降解。在无白蛋白的细胞系统中，细胞活力结果表明FeTPPS对活细胞无害，可以保护细胞免受H ₂ O ₂的氧化损伤有效地而不是促进损害。使用蛋白质印迹，我们证明了FeTPPS不能诱导HO-1的表达，这表明HO-1与FeTPPS的保护能力无关。我们的结果提供了对FeTPPS的更好理解，并为其应用提供了新的指导。