Redox status and accumulation of autophagosomes in the liver of mouse under the action of lithium chloride

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Abstract

Activation of autophagy is considered one of the promising strategies for the treatment and prevention of various non-infectious liver diseases. In this work, we assessed the changes in redox status and autophagy activation in liver tissues in vivo under the action of lithium chloride. It was shown that lithium chloride leads to the accumulation of autophagosomes in liver cells under normal conditions. This process is accompanied by a slight increase in the activity of several antioxidant enzymes. Toxic effects on the liver and the development of oxidative stress with 3-day use of LiCl were not detected. Significant rearrangements in the ultrastructure of the endoplasmic reticulum were observed, which can play a signaling role and participate in the initiation of autophagy. Thus, oral application of lithium chloride can be used as an effective modulator of the autophagy process in liver tissues.

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About the authors

S. А. Dmitrieva

FRC Kazan Scientific Center, Russian Academy of Sciences

Author for correspondence.
Email: s_dmitrieva@list.ru

Kazan Institute of Biochemistry and Biophysics

Russian Federation, 420111, Kazan

A. A. Ponomareva

FRC Kazan Scientific Center, Russian Academy of Sciences

Email: s_dmitrieva@list.ru

Kazan Institute of Biochemistry and Biophysics

Russian Federation, 420111, Kazan

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2. Fig. 1. General appearance of mouse liver cells exposed to LiCl at different concentrations: a – control, b – 5 mg/kg, c – 10 mg/kg, d – 15 mg/kg. Scale bar: 5 µm. Legend: af – autophagosome, b – bile capillary, ki – Ito cell, kk – Kupffer cell, l – lysosome, lk – lipid droplet, m – mitochondrion, ds – Disse space, sc – sinusoidal capillary, sr – rough endoplasmic reticulum, n – nucleus, n – nucleolus.

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3. Fig. 2. Formation of autophagosomes in mouse hepatocytes under the action of LiCl in different concentrations: a – control, b – 5 mg/kg, c – 10 mg/kg, d – 15 mg/kg. Scale bar: 1 μm (a–c) and 0.5 (d) μm. Designations: al – autolysosome, ag – Golgi apparatus, sr – smooth endoplasmic reticulum, p – peroxisome, β – ribosomes. Other designations are the same as in Fig. 1.

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4. Fig. 3. Changes in the ultrastructure of mitochondria and endoplasmic reticulum in mouse hepatocytes under the action of LiCl in different concentrations: a – control, b – 5 mg/kg, c – 10 mg/kg, d – 15 mg/kg. Scale bar: 1 µm. Designations are the same as in Fig. 1, 2. The arrow indicates the contact zones of the dilated ER tubules with the mitochondria.

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5. Fig. 4. Activity of superoxide dismutase (SOD, a), catalase (CAT, b), glutathione peroxidase (GPx, c) and glutathione reductase (GR, d) in liver tissues after application of LiCl for three days. Average values ​​and their standard deviations (per 1 mg protein) are shown. Differences relative to the control (*) and between variants (#) are significant at P < 0.05; (n = 6, nonparametric Mann–Whitney test).

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