Veterans Affairs Medical Center and Virginia Tech, Carilion School of Medicine, Salem, VA 24153, USA.
GP Livanos and M Simou Laboratories, Evangelismos Hospital, 1st Department of Critical Care Medicine & Pulmonary Services, National and Kapodistrian University of Athens, 10675 Athens, Greece.
Int J Mol Sci. 2023 Apr 6;24(7):6815. doi: 10.3390/ijms24076815.
Renal immune injury is a frequent cause of end-stage renal disease, and, despite the progress made in understanding underlying pathogenetic mechanisms, current treatments to preserve renal function continue to be based mainly on systemic immunosuppression. Small molecules, naturally occurring biologic agents, show considerable promise in acting as disease modifiers and may provide novel therapeutic leads. Certain naturally occurring or synthetic Metalloporphyrins (Mps) can act as disease modifiers by increasing heme oxygenase (HO) enzymatic activity and/or synthesis of the inducible HO isoform (HO-1). Depending on the metal moiety of the Mp employed, these effects may occur in tandem or can be discordant (increased HO-1 synthesis but inhibition of enzyme activity). This review discusses effects of Mps, with varying redox-active transitional metals and cyclic porphyrin cores, on mechanisms underlying pathogenesis and outcomes of renal immune injury.
肾脏免疫损伤是终末期肾病的常见病因,尽管在理解潜在发病机制方面取得了进展,但目前用于保护肾功能的治疗方法仍主要基于全身免疫抑制。小分子、天然存在的生物制剂在作为疾病修饰剂方面显示出很大的潜力,并可能提供新的治疗线索。某些天然存在或合成的金属卟啉(Mps)可以通过增加血红素加氧酶(HO)酶活性和/或诱导型 HO 同工型(HO-1)的合成来充当疾病修饰剂。根据所使用的 Mp 的金属部分,这些作用可以同时发生,也可以不一致(增加 HO-1 合成但抑制酶活性)。这篇综述讨论了具有不同氧化还原活性过渡金属和环状卟啉核心的 Mps 对肾脏免疫损伤发病机制和结果的影响。