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Updated: Jul 9, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
[Liver steatosis and disorders of mitochondrial oxidative phosphorylation after experimental administration of
O Vancova1, O Ulicna, J Horecky
1Laboratory of Pharmacobiochemistry, IIIrd Dpt of Internal Medicine, Hlboka 7, SK-811 05 Bratislava 1, Slovakia. bll@fmed.uniba.sk
Background:
Triazine herbicides are widely used in extensive agricultural production, however, some ecological and health hazards occur due to water and food contamination.
Aim:
The aim of this study was to evaluate the effects of long-term simazine feeding on the steatosis development and the changes of liver bioenergetics in experimental animals.
Methods:
A population of B6C3F1 mice were fed with simazine (2 g and 4 g/kg/day, respectively) for 35 weeks. The concentration of cholesterol and triacylglycerols were measured in liver tissue. Liver mitochondria were isolated and parameters of oxidative phosphorylation were assessed polarographically using Clark oxygen electrode with NAD glutamate and/or FAD succinate as substrates.
Results:
Significant changes (p < 0.001) expressed as medians (with confidence intervals) against control animals were found in both experimental groups after simazine feeding. The concentration of triacylglycerols increased from 10.3 (8.8-10.9) to 20.1 (18.0-20.9) and 47.7 (23.8-56.0), respectively. The parameters of oxidative phosphorylation with NAD substrate glutamate decreased as follows: The index of respiratory control from 7.7 (6.4-9.0) to 4.8 (4.0-6.3) resp. 4.4 (3.9-4.6); the rate of oxygen consumption in the state 3 (with ADP) from 84.2 (82.0-92.3) to 65.4 (50.8-70.7) resp. 69.9 (65.0-78.4) nAtO.mg.prot-1.min-1; and phosporylation rate from 215.3 (204.4-232.2) to 166.3 (120.4-193.6) resp. 169.6 (155.3-176.9) nmolATP.mg.prot-1.min-1. Comparable changes were detected in oxidative phosphorylation with FAD succinate as substrate.
Conclusions:
Liver steatosis development and mitochondrial energetics inhibition were determined in mice after long-term simazine feeding, nevertheless, liver energy production was sufficient to satisfy the liver function and the needs of the whole organism. (Tab. 4, Fig. 6, Ref. 24.)
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