Evaluating Drug-Induced Liver Injury and Its Remission via Discrimination and Imaging of HClO and H₂S with a Two-Photon Fluorescent Probe

Abstract

Drug-induced liver injury (DILI) has aroused wide concern. Finding new markers or indicators as well as detoxification molecules for DILI is of great significance and good application prospect, which can help develop effective preclinical screening methodology and corresponding treatment protocols. Herein, in this article, DILI caused by antidepressant drugs of duloxetine and fluoxetine and its remission were evaluated by a two-photon fluorescent probe, RPC-1, through discriminating and imaging HClO and HS simultaneously. By being applied both in vitro and in vivo, RPC-1 revealed slight up-regulation of HClO and negligible liver damage after administration of either of the two drugs. In contrast, an apparent up-regulation of HClO and obvious liver damage was observed after combined administration of the drugs. Meanwhile, the pretreatment of N-acetyl cysteine (NAC) resulted in the increasing of endogenous HS level, which contributed to the remission of DILI. The histological analysis and serological test both gave good consistency with the imaging results. These findings demonstrate that HClO may be an appropriate indicator of DILI, and HS plays an important role in the antidotal effect of NAC. We envision that RPC-1 can be used as a powerful tool to predict clinical DILI and study the effect of antidote, as well as explore the molecular mechanisms involved.

Chiral CuxOS@ZIF‐8 Nanostructures for Ultrasensitive Quantification of Hydrogen Sulfide In Vivo

“…[ 2 ] The abnormal regulation of H 2 S has also been shown to be associated with diabetes, liver cirrhosis, and several other diseases. [ 3–5 ] Therefore, the development of methods with which to monitor H 2 S accurately in biological systems is very important and is receiving increasing levels of research attention. Thus far, a variety of approaches have been used to detect and track H 2 S in biological systems, including colorimetric methods, [ 6 ] electrochemical analysis, [ 7 ] surface‐enhanced Raman scattering, [ 8 ] and fluorescence assays.…”

Evaluation of HOCl-generating anticancer agents by an ultrasensitive dual-mode fluorescent probe

“…Next, the potential for probes C6 and C7 to detect endogenous HOCl in live cells was evaluated. Bacterial endotoxin lipopolysaccharide (LPS) is known to induce cellular apoptosis and release ROS, including HOCl 32–34. HepG2 cells and A549 cells were pretreated with LPS for three hours, and the stimulated cells were then incubated with C6 and C7 (20 μM), respectively.…”

Tumor-acidity activated surface charge conversion of two-photon fluorescent nanoprobe for enhanced cellular uptake and targeted imaging of intracellular hydrogen peroxide

“…Fluorescence imaging, particularly using two-photon microscopy (TPM), provides a powerful tool for selective, noninvasive and real-time monitoring of ROS in biological systems with high spatial resolution, deep tissue penetration and low phototoxicity. [8][9][10][11][12][13][14][15][16][17][18][19][20][21] To date, several two-photon uorescence probes have been reported for imaging H 2 O 2 in living cells and tissues. [22][23][24][25] The "turn on" uorescence of these probes mainly arises from the oxidative reaction or oxidative rearrangement of the reaction site upon exposure to H 2 O 2 .…”