Effects of Acute Administration of D,L-Homocysteine Thiolactone on the Antioxidative Status of Rat Intestine and Liver

Abstract

Oxidative stress appears to play a role in the pathogenesis of several infl ammatory gastrointestinal diseases. Increased homocysteine levels may play a role in the pathogenesis of Chron's disease and ulcerative colitis. The aim of this study was to examine the infl uence of homocysteine on the antioxidant status of rat intestine and liver. The levels of thiobarbituric acid reactive substances (TBARS), activity of catalase (CAT) and total antioxidant status (TAS) were investigated in the isolated gut and liver of young male rats in the control group (8 rats) and after 3-hоur incubation in high doses of D, L-homocysteine thionolactone (Hcy) (10 μmol/L) (8 rats). Samples of duodenum, ileum, colon and liver were homogenized in sodium phosphate buffer (1:10). Homogenates were centrifuged at 10000 for 10 min at 4 0 C and the supernatant was taken for biochemical assays. Our results showed that high D, L-homocysteine thionolactone concentration reduced enzymatic catalase activity in homogenates of the isolated segments of duodenum (27.04%) p<0.01; ileum (37.27%), colon (34.17%) and liver (67.46%) p<0.001. Exposition to high D,L-homocysteine thiolactone concentration signifi cantly increased TBARS levels in the duodenum (106.05%), ileum (47.24%), colon (112.75%) and liver (32.07%) (p<0.01). Homocysteine also modifi ed the total antioxidant status of homogenates from the duodenum, ileum, colon and liver, increasing by 20.68% (duodenum), 24.74% (ileum), 14.88% (colon) and 19.35% (liver) (p<0.001). Homocysteine induced a consistent oxidative stress in rat's intestine and liver (reduced activity of catalase and increased level of TBARS), but the elevated activity of TAS in our experiments could be explained as an adaptive response to the generated free radicals which indicates the failure of the total antioxidant defense mechanism to protect the tissues from damage caused by homocysteine.

Histological and histochemical changes in liver tissue of young rats with hyperhomocysteinemia

“…According to studies by M. Stojanovic et al [16] D, L-Hcy thiolactone when administered to rats contributes to the development of oxidative stress in hepatocytes and the reduction of antioxidant defense reserves. The authors registered inhibition of catalase activity in the liver tissue of laboratory animals.…”

Single-Step Hydrolysis and Derivatization of Homocysteine Thiolactone Using Zone Fluidics: Simultaneous Analysis of Mixtures with Homocysteine Following Separation by Fluorosurfactant-Modified Gold Nanoparticles

“…HTL is a chemically reactive metabolite generated by methionyl-tRNA synthetase and cleared by the kidney [ 5 ]. There are numerous recent studies trying to elucidate the role of HTL in human health, including the oxidative status of liver and intestines [ 6 ], sperm function [ 7 ], blood vessel disfunction [ 8 ], and cardiovascular diseases [ 9 ].…”

Features of histological changes in the lungs of mature animals under conditions of hyperhomocysteinemia

“…The increase in its content in the blood is accompanied by a number of negative changes in organs and systems, one of which is endothelial damage. The realization of this effect is carried out by apoptosis and accelerated aging of endothelial cells [8,11,17]. In addition, homocysteine acts as a procoagulant, inhibiting the activity of antithrombin III, heparin and increases the activity of thrombin, which ultimately creates the basis for the development of thrombosis.…”