Effects of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on the oxidative status and activity of dicarboxylic acid metabolism enzymes in toxic liver injury in rats

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Abstract

One of the widespread public health problems nowadays is toxic liver damage. The key mechanism of the pathogenic action of xenobiotics One of the widespread public health problems nowadays is toxic liver damage. The key mechanism of the pathogenic action of xenobiotics on the liver is the activation of oxidative stress. Excessively generated free radicals damage mitochondrial components in hepatocytes, which can lead to disfunction of mitochondrial dehydrogenases.

The aim of the work was to investigate the influence of antioxidant 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on oxidative status, activity of succinate dehydrogenase and NAD-dependent malate dehydrogenase in rats with toxic liver damage.

Material and methods. The study included 48 male Wistar rats weighing 200-250 g, divided into 4 groups of 12 animals in each: control group, a group of animals with tetrachloromethane-induced liver damage, rats with pathology that received intragastrically 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline at a dose of 50 mg/kg, and control rats received the tested compound. The level of oxidative modification of proteins was assessed by the method of Reznick et al. with slight modifications, alpha-tocopherol concentration was estimated by the method based on measuring the absorption of chromogenic complex compound Fe2+ and orthophenanthroline. Activity of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltranspeptidase was determined in blood serum using Olvex Diagnosticum reagent kits (Russia, Saint Petersburg). Cytoplasmic and mitochondrial liver fractions were obtained for analysis of succinate dehydrogenase and NAD-dependent malate dehydrogenase activity.

Results. Results of the work have shown that 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline treatment led to the normalization of the analyzed parameters, which was apparently due to the correction of the redox status in the liver of animals under the action of the tested compound.

Conclusion. The results of the study make it necessary to further investigate the effect of dihydroquinoline derivatives on oxidative metabolic enzymes in pathological

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About the authors

D. A. Sinitsyna

Voronezh State University

Author for correspondence.
Email: evgenij.krylsky@yandex.ru

Post-Graduate Student, Department of Medical Biochemistry and Microbiology

Russian Federation, Voronezh

T. N. Popova

Voronezh State University

Email: evgenij.krylsky@yandex.ru

Dr.Sc. (Biol.), Professor, Dean of Medical and Biological Faculty

Russian Federation, Voronezh

E. D. Kryl’skii

Voronezh State University

Email: evgenij.krylsky@yandex.ru

Ph.D. (Biol.), Associate Professor, Department of Medical Biochemistry and Microbiology

Russian Federation, Voronezh

Kh. S. Shikhaliev

Voronezh State University

Email: evgenij.krylsky@yandex.ru

Dr.Sc. (Chem.), Professor, Head of Organic Chemistry Department

Russian Federation, Voronezh

Ju. I. Lebedeva

Voronezh State University

Email: evgenij.krylsky@yandex.ru

Student, Department of Medical Biochemistry and Microbiology

Russian Federation, Voronezh

E. V. Zherebtsova

Voronezh State University

Email: evgenij.krylsky@yandex.ru

Student, Department of Medical Biochemistry and Microbiology

Russian Federation, Voronezh

D. A. Popova

Voronezh State University

Email: evgenij.krylsky@yandex.ru

Student, Department of Medical Biochemistry and Microbiology

Russian Federation, Voronezh

References

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Supplementary files

Supplementary Files
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1. JATS XML
2. Figure 1. Activity of alanine aminotransferase (Alat), aspartate aminotransferase (Asa) and gamma-glutamyl transpeptidase (GGTP) in the blood serum of experimental animals. Here and in fig. 2–4: Control - control group; TPP - animals with toxic liver damage; TPP+DHC – rats treated with 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline at a dose of 50 mg/kg against the background of pathology; Control + DHC - control group of rats treated with 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline at a dose of 50 mg/kg; * - significant differences from the control group, ** - significant differences from the group of animals with pathology, p<0.05

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3. Figure 2. The level of oxidative modification of proteins in the liver and blood serum of experimental animals

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4. Figure 3. The level of α-tocopherol in the liver and blood serum of experimental animals

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5. Figure 4. Activity of succinate dehydrogenase in mitochondria (a) and NAD-dependent malate dehydrogenase in mitochondrial (b) and cytoplasmic (c) fractions of the liver of experimental animals

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