Abstract
Abstract A new formulation (niosomes) was prepared to enhance the bioavailability, hepatic tissue uptake, and hepatoprotective activity of glutathione (GSH). The GSH-loaded niosomes (nanoform, N-GSH) were formulated by the thin-film hydration technique using cholesterol/non-ionic surfactants (Span®40, Span®60, and Tween®80) at a componential ratio of 1:1 and 2:1. The hepatoprotective activity of N-GSH, GSH, and the standard silymarin against CCl4-induced liver damage and oxidative stress were tested on the rats’ model. The hepatic morphology and histopathological characters were also investigated. The tissue contents of N-GSH were analysed using a concurrently validated RP-HPLC method. The optimized niosomes, composed of glutathione (500 mg), cholesterol, and Span®60-Tween®80 at a molar ratio of 2:1 of cholesterol/non-ionic surfactant, displaying a particle size of 688.5 ± 14.52 nm, a zeta potential of −26.47 ± 0.158 mV, and encapsulation efficiency (EE) of 66 ± 2.8% was selected for in vivo testing. The levels of MDA, NO, SOD, NF-κB, IL-1β, and Bcl-2 were measured. The results demonstrated that hepatic tissue damage was ameliorated using N-GSH as confirmed by the morphological and histopathological examination compared to the CCl4 and control groups. The N-GSH significantly (p < 0.05) decreased the elevated levels of hepatic enzymes, oxidative parameters, and inflammatory mediators, as compared to silymarin and GSH. Also, N-GSH significantly (p < 0.05) increased GSH hepatocyte concentrations as compared to the control groups. The present study demonstrated that N-GSH remarkably improved glutathione oral bioavailability and hepatic tissue uptake, thereby introducing a new glutathione formulation to protect hepatic tissue from injury and restore its GSH contents.
Highlights
Liver-associated illnesses remain a global health concern
The present study demonstrated that N-GSH remarkably improved glutathione oral bioavailability and hepatic tissue uptake, thereby introducing a new glutathione formulation to protect hepatic tissue from injury and restore its GSH contents
The CCl4 exposure generates excessive amounts of nitric oxide (NO) by activating the iNOS, contributing to hepatic tissue damages [64], an observation circumstantially consistent with the present study’s findings. These results revealed that the oral administration of N-GSH dramatically decreased NO concentrations in the hepatic tissue, thereby contributing to its antioxidant and anti-inflammatory actions
Summary
Liver-associated illnesses remain a global health concern. These diseases are considered to be the leading cause of mortality among populations of low- to middle-income Asian and African countries [1]. The liver is highly susceptible to oxidative stress, inflammation, and degeneration since it is the main organ responsible for the metabolism and detoxification of nutrients/drugs [2]. Several physiological and pathological processes in human and animal cells, e.g. gene expression, signal transduction, growth, and even death, are associated with reactive oxygen species (ROS) production [3]. This work is licensed under the Creative Commons Attribution 4.0.
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