Relationship between content of hepatic glutathione S‐transferases and the kinetics of indocyanine green elimination in various liver diseases

“…The combination of a very high level expression of GSTs in several tumor cells and normal tissues and high affinity binding suggests the possibility that HYP uptake by cells could be affected by GST expression. Indeed, it has been suggested that cellular uptake and localization of hematoporphyrin and indocyanine dyes are altered by expression of, and binding to, GSTs ( − ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Antioxidant Role for Ligandin Behavior of Glutathione S-Transferases: Attenuation of the Photodynamic Effects of Hypericin

Atkins

2004

Biochemistry

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Hypericin (HYP) is a major constituent of the herbal antidepressant St. John's wort with potential utility as an antitumor photodynamic sensitizer and antiviral agent. Upon irradiation at 540-600 nm, HYP generates reactive oxygen species (ROS) and induces oxidative stress. Here, human glutathione S-transferase (GST) isoforms GSTP1-1 (P1-1) and GSTA1-1 (A1-1) are shown to bind with high affinity to HYP and to differentially quench its photodynamic properties. In steady-state turnover studies, HYP inhibits A1-1 and P1-1 with IC(50) values of 160 and 190 nM, respectively. Fluorescence titration experiments and fitting of the data to the Hill equation yield apparent K(D)s for binding to A1-1 and P1-1 of 0.65 and 0.51 microM, respectively. The recovered Hill coefficients are 1.8 for both GSTA1-1 and GSTP1-1, indicating that multiple HYPs bind to each isoform. This behavior is reminiscent of classic "ligandin" activity of GSTs, wherein nonsubstrate planar aromatic anions are sequestered on, and inhibit, the enzyme. However, HYP complexed with P1-1 is photodynamically attenuated, with minimal protein oxidation. In contrast, light-dependent, oxygen-dependent, oxidation of A1-1 was modest and oxidation of human albumin was extensive in the presence of HYP, as monitored by electrospray mass spectrometry (ESI-MS). A peptide "trap" of diffusive ROS was oxidized extensively upon irradiation of HYP in the presence of albumin but very little in the presence of P1-1 or A1-1. Solute quenching studies were used to probe the accessibility of the bound HYP in each of the protein complexes. The fluorescence of HYP complexed with albumin, A1-1, or P1-1 was quenched by I(-) with quenching rate constants (k(q)) of 1.1 x 10(9), 2.4 x 10(9) and 0.5 x10(9) M(-1) s(-1), respectively, indicating that small molecules such as O(2) have similar diffusional access to the complexed HYP in each of the proteins, eliminating the possibility of differential accessibility of oxygen as the source of a different yield of ROS. This is the first demonstration of a possible antioxidant role for the ligandin activity of GSTs and a striking example of protein-specific effects on hypericin photodynamic activity. Even highly homologous protein isoforms can differentially promote or inhibit photosensitizer activity.

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Stability and degradation of indocyanine green in plasma, aqueous solution and whole blood

Mindt

Karampinis

John

et al. 2018

Photochem Photobiol Sci

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Fluorescence-based imaging has evolved into an important technology during recent years. Specifically indocyanine green (ICG) has invaded most fields of diagnostic and interventional medicine. Considering the numerous advantages of the substance like the rapid degradation and rare adverse reactions, ICG is currently the most commonly used fluorescing agent. High-performance liquid chromatography (HPLC) was used for measuring absorbance and fluorescence of ICG and its potential degradation compounds. Stability and degradation were evaluated under light exposure or in darkness at various temperatures. Under these conditions, degradation of ICG was evaluated over a period of 11 days. Additional, stability measurements of ICG were performed in EDTA whole blood samples at 37 °C incubation temperature while monitoring. Furthermore, we used mass spectrometric (MS) and nuclear magnetic resonance (NMR) analyses for the identification of supposed ICG degradation compound. Potential quenching effect of ICG was examined in aqueous and plasma solutions at concentrations ranging from 0.01-100 μg ml-1. When diluted in water and stored at 4 °C in the dark, ICG is stable for three days with only 20% of fluorescence intensity lost in this time-span. ICG incubated at 37 °C in whole blood under light exposure is stable for 5 h. In our study we observed the degradation of ICG into two degradation compounds with a mass of m/z 785.32 and m/z 1501.57, respectively. Based on our observations we suggest that ICG should be used within one or two days after preparation, if the ICG solution is stored at 4 °C.

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Relationship between content of hepatic glutathione S‐transferases and the kinetics of indocyanine green elimination in various liver diseases

Cited by 6 publications

References 19 publications

Influence of GSTT1 and GSTM1 Genotypes on Sunburn Sensitivity

Influence of GSTT1 and GSTM1 Genotypes on Sunburn Sensitivity

A Novel Antioxidant Role for Ligandin Behavior of Glutathione S-Transferases: Attenuation of the Photodynamic Effects of Hypericin

Stability and degradation of indocyanine green in plasma, aqueous solution and whole blood

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