Metalloporphyrins as Tools for Deciphering the Role of Heme Oxygenase in Renal Immune Injury

Abstract

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.

Keywords: heme oxygenase; immune mediated; renal injury.

Figure 1

Metalloporphirn (Mps) types. Schematic representation of the chemical structure of Mp molecules depending on the ring substituents (lower right and upper right) and the central metal moiety. Porphyrins catalyzed by HO are oxidized at the α-position (red colour) to yield a tetrapyrrole. Modified from Vreman et al. (2001) [22].

Figure 2

Effect of Mps on HO reaction and HO-1 expression and activity. Schematic representation of the HO reaction and the in vivo effect of various Mps which, depending on metal moiety, act either as HO activators/inducers (FePP and cobalt protoporphyrin, CoPP) or HO activity inhibitors (ZnPP, SnPP and tin mesoporphyrin, SnMP). Mps may also have a differential effect on HO-1 expression and activity in vivo.