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Wen-Pi-Tang, a traditional Chinese prescription, has been widely used for the treatment of patients with moderate chronic renal failure in China. Although the protective effect of Wen-Pi-Tang on peroxynitrite (ONOO^-)-induced renal tubular epithelial LLC-PK₁ cell damage was elucidated in our previous research, the active components of Wen-Pi-Tang have not yet been fully clarified. Therefore in the present study, we investigated the active components by using a cellular ONOO^-generation system. As a result, p-coumaric acid, 4-(4'-hydroxylphenyl)-2-butanone 4'-O-glucopyranoside, gallic acid 3-O-(6'-O-galloyl)-β-d-glucopyranoside, procyanidin B-1, procyanidin B-3, and (+)-catechin were isolated as active compounds inhibiting cellular ONOO^- formation and cytotoxicity. In particular, the content of (+)-catechin was significantly higher than those of the other compounds, and the (+)-catechin structure was located in procyanidins B-1 and B-3. Therefore, the major bioactivity of Wen-Pi-Tang against ONOO^--induced cytotoxicity in LLC-PK₁ cells was thought to be mediated by (+)-catechin. Although we cannot disregard the synergetic effect of various components in Wen-Pi-Tang, (+)-catechin is a major active compound protecting against ONOO^--induced LLC-PK₁ cell damage and may be used as an index to qualify the ONOO^--inhibitory activity of Wen-Pi-Tang extract.

Following up on the characterization of a new (heme)Fe^III-superoxide species formed from the cryogenic oxygenation of a ferrous-heme (P^Py)Fe^II (1) (P^Py = a tetraarylporphyrinate with a covalently tethered pyridine group as a potential axial base), giving (P^Py)Fe^III-O₂^•- (2) (Li Y et al., Polyhedron 2013; 58: 60–64), we report here on (i) its use in forming a cytochrome c oxidase (CcO) model compound, or (ii) in a reaction with nitrogen monoxide (•NO; nitric oxide) to mimic nitric oxide dioxygenase (NOD) chemistry. Reaction of (2) with the cuprous chelate [Cu^I(AN)][B(C₆F₅)₄] (AN = bis[3-(dimethylamino)propyl]amine) gives a meta-stable product (3a), possessing a high-spin iron(III) and Cu(II) side-on bridged peroxo moiety with a μ-η²:η²-binding motif. This complex thermally decays to a corresponding μ-oxo complex [(P^Py)Fe^III-(O^2-)-Cu^II(AN)][B(C₆F₅)₄] (3). Both (3) and (3a) have been characterized by UV-vis, ²H NMR and EPR spectroscopies. When (2) is exposed to •NO_(g), a ferric heme nitrato compound forms; if 2,4-di-tert-butylphenol is added prior to •NO_(g) exposure, phenol ortho-nitration occurs with the iron product being the ferric hydroxide complex (P^Py)Fe^III(OH) (5). The latter reactions mimic the action of NOD's.

Peroxynitrite (ONOO${}^{-})$ contributes to oxidative stress and neurodegeneration in Parkinson’s disease (PD). Developing a peroxynitrite probe would enable in situ visualization of the overwhelming ONOO⁻ flux and understanding of the ONOO⁻ stress-induced neuropathology of PD. Herein, a novel $\alpha$-ketoamide-based fluorogenic probe ( DFlu) was designed for ONOO⁻ monitoring in multiple PD models. The results demonstrated that DFlu exhibits a fluorescence turn-on response to ONOO⁻ with high specificity and sensitivity. The efficacy of DFlu for intracellular ONOO⁻ imaging was demonstrated systematically. The results showed that DFlu can successfully visualize endogenous and exogenous ONOO⁻ in cells derived from chemical and biochemical routes. More importantly, the two-photon excitation ability of DFlu has been well demonstrated by monitoring exogenous/endogenous ONOO⁻ production and scavenging in live zebrafish PD models. This work provides a reliable and promising $\alpha$-ketoamide-based optical tool for identifying variations of ONOO⁻ in PD models.

The following sections are included:

• Introduction

• Glutathione Peroxidase and Oxidant Interception Reactions

• Peroxynitrite, Oxidative Stress and Aging

• Protection Against Peroxynitrite by Organoselenium Compounds

• Protection Against Peroxynitrite by Selenoproteins

• Potential Protection Against Aging by Pharmacologic/Nutritive Supplementation with Organoselenium Compounds

• Acknowledgments

• References