Abstract

The liver failure means inability to perform its normal synthetic, biotransformation and excretory functions. The disturbance of metabolic processes leads to the development of "metabolic endogenous intoxication" resulting in oxidative stress. Oxidative stress initiates the processes of oxidation of amino acid residues of blood plasma proteins causing the changes in their structure and functions. The effect of administration of highly activated porous carbonic enterosorbents on oxidative stress manifestations and molecular conformation of serum albumin in blood of experimental animals with acute liver failure induced by carbon tetrachloride (CCl4) needs to be investigated. Two forms of activated carbonic enterosorbents such as AC1 (primary beads with the range of diameters of 125–250 μm) and AC2 (secondary granules prepared from micronized AC1 having the mean particle size of ~1 μm) derived from phenol-formaldehyde resin were used in rat model with CCl4 intoxication. The total level of reactive oxygen species (ROS) in blood plasma, the activity of catalase (CAT) in blood hemolysates; the content of reduced glutathione (GSH) in liver homogenates, and the level of oxidative modification of proteins (OMP) such as aldehyde-dinitrophenylhydrazone (A-DNPH) and ketone-dinitrophenylhydrazone (K-DNPH) derivatives in blood plasma and liver homogenates were determined. In addition, the level of pro/antioxidant ratio in blood hemolysates and the content of lipid peroxidation product - malondialdehyde (MDA), in blood plasma and liver were determined. Melting thermograms of blood plasma proteins (BPP) and molecular conformation changes of serum albumin were analyzed by biophysical methods (differential scanning microcalorimetry and spectrofluorimetry). The extent of CCl4-induced oxidative damage in blood and liver of experimental animals was shown to be less expressed for AC1 in comparison with AC2 enterosorbent. However, AC2 used in the form of secondary granules positively influenced some biophysical properties of albumin molecule (temperature of melting, shape of melting endotherm and intrinsic fluorescence) after rats exposure to CCl4. In general, administration of both AC1 and AC2 led to the reduction of oxidative stress manifestations and partial restoration of native molecular conformation of serum albumin. These observations are promising in terms of achieving recovery of detoxification potential of organism after severe liver injury.

Highlights

  • Carbon tetrachloride (CCl4) is widely used in in vivo liver injury models, and the damage induced by CCl4 is comparable to that observed with viral hepatitis

  • If AC1 sharply reduced the content of GSH, and its level in the liver exceeded the control just by 1.19 times, AC2 exerted weak influence on this index, and it remained elevated by 1.83 times

  • Result of AC2 usage completely coincided with intact rats MDA level

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Summary

Introduction

Carbon tetrachloride (CCl4) is widely used in in vivo liver injury models, and the damage induced by CCl4 is comparable to that observed with viral hepatitis. CCl4 is transformed into a toxic trichloromethyl radical, CCl3 by CYP2E1, an enzyme expressed in perivenular hepatocytes [1] This radical can bind to various cellular molecules impairing crucial processes of a cell, such as lipids metabolism, with the potential outcome of fatty degeneration (steatosis). By reacting with oxygen this radical transforms into the highly reactive trichloromethylperoxy radical CCl3OO that initiates the chain reaction of lipid peroxidation and damages polyunsaturated fatty acids, in particular those associated with phospholipids. These effects can result in the altered permeability of cells membranes, mitochondria [2], and endoplasmic reticulum, causing deregulation of calcium sequestration and homeostasis, which are indispensable for the normal cell functions [3]. The oxidative stress caused due to CCl4-induced free radical production is considered to be one of the main mechanism by which the hepatocellular damage is taking place [4, 5]

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