Menu

A+ A A-

Download article

DOI: https://doi.org/10.22263/2312-4156.2021.6.23

Kondratovich I.A., Andreev V.P., Kravchuk R.I., Gulyai I.E., Shalesnaya S.Ya., Tsyrkunov V.M.
The effect of retinol on the development of thioacetamide-induced fibrosis in rats
Grodno State Medical University, Grodno, Republic of Belarus

Vestnik VGMU. 2021;20(6):23-34.

Abstract.
Perisinusoidal lipocytes, which store retinol and its derivatives in their lipid droplets, play a leading role in the development of liver fibrosis (LF).
Objectives. To assess the effect of retinol on the development of thioacetamide (TAA) -induced LF in rats.
Material and methods. The experiment was conducted on 48 male rats, represented by 6 groups. A 10 ml/kg TAA solution (2%) was administered intraperitoneally every other day. A retinol oil solution (800 IU/kg) in sunflower oil was given once a day. Two control groups received saline solution (1) and sunflower oil (2). Light and electron microscopy of the obtained semi- and ultrathin sections of the liver tissue was performed, the relative content of the connective tissue in the liver preparations was morphometrically evaluated, the content of retinol in blood plasma and the liver was determined.
Results. Morphological studies of the control animals liver revealed the presence of a typical beam structure. 4 weeks after daily administration of retinol, the beam structure of the liver persisted, but lymphohistiocytic infiltration of portal tracts and disseminated intralobular infiltration were noted; there were inflammatory foci with a large number of cellular elements; the amount of the connective tissue significantly increased. After 4 weeks of TAA administration, a pronounced inflammatory reaction was observed in the central vein region, with the penetration into the lobe, the degree of fibrosis increased with the formation of thin incomplete septs. 4-week administration of retinol after 4-week TAA exposure led to increased fibrotic processes in the liver compared to animals treated with TAA alone. 8-week administration of TAA with 4-week administration of retinol resulted in 14-fold increase in the degree of fibrosis compared to control animals.
Conclusions. The application of retinol in the used experimental dose stimulates the fibrosis process in rats’ liver.
Key words: rats, thioacetamide, liver fibrosis, perisinusoidal lipocytes, retinol.

References

1. Kisseleva T, Brenner DA. Inactivation of myofibroblasts during regression of liver fibrosis. Cell Cycle. 2013 Feb 1;12(3):381-2. doi: http://dx.doi.org/10.4161/cc.23549
2. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005 Feb;115(2):209-18. doi: http://dx.doi.org/10.1172/JCI24282
3. Senoo H, Kojima N, Sato M. Vitamin A-storing cells (stellate cells). Vitam Horm. 2007;75:131-59. doi: http://dx.doi.org/10.1016/S0083-6729(06)75006-3
4. Tcyrkunov VM, Andreev VP, Kravchuk RI, Kondratovich IA. Clinical cytology of the liver: stellate cells Ito. Zhurn GrGMU. 2016;(4):90-9. (In Russ.)
5. Yavuz BG, Pestana RC, Abugabal YI, Krishnan S, Chen J, Hassan MM, et al. Origin and role of hepatic myofibroblasts in hepatocellular carcinoma. Oncotarget. 2020 Mar 31;11(13):1186-1201. doi: http://dx.doi.org/10.18632/oncotarget.27532
6. Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol. 2021 Mar;18(3):151-166. doi: http://dx.doi.org/10.1038/s41575-020-00372-7
7. Jophlin LL, Koutalos Y, Chen C, Shah V, Rockey DC. Hepatic stellate cells retain retinoid-laden lipid droplets after cellular transdifferentiation into activated myofibroblasts. Am J Physiol Gastrointest Liver Physiol. 2018 Nov;315(5):G713-G721. doi: http://dx.doi.org/10.1152/ajpgi.00251.2017
8. Delire B, Stärkel P, Leclercq I. Animal Models for Fibrotic Liver Diseases: What We Have, What We Need, and What Is under Development. J Clin Transl Hepatol. 2015 Mar;3(1):53-66. doi: http://dx.doi.org/10.14218/JCTH.2014.00035
9. Davis BH, Kramer RT, Davidson NO. Retinoic acid modulates rat Ito cell proliferation, collagen, and transforming growth factor beta production. J Clin Invest. 1990 Dec;86(6):2062-70. doi: http://dx.doi.org/10.1172/JCI114943
10. Senoo H, Wake K. Suppression of experimental hepatic fibrosis by administration of vitamin A. Lab Invest. 1985 Feb;52(2):182-94.
11. Seifert WF, Bosma A, Hendriks HF, van Leeuwen RE, van Thiel-de Ruiter GC, Seifert-Bock I, et al. Beta-carotene (provitamin A) decreases the severity of CCl4-induced hepatic inflammation and fibrosis in rats. Liver. 1995 Feb;15(1):1-8. doi: http://dx.doi.org/10.1111/j.1600-0676.1995.tb00098.x
12. Leo MA, Lieber CS. Hepatic fibrosis after long-term administration of ethanol and moderate vitamin A supplementation in the rat. Hepatology. 1983 Jan-Feb;3(1):1-11. doi: http://dx.doi.org/10.1002/hep.1840030101
13. Okuno M, Moriwaki H, Imai S, Muto Y, Kawada N, Suzuki Y, et al. Retinoids exacerbate rat liver fibrosis by inducing the activation of latent TGF-beta in liver stellate cells. Hepatology. 1997 Oct;26(4):913-21. doi: http://dx.doi.org/10.1053/jhep.1997.v26.pm0009328313
14. Seifert WF, Bosma A, Brouwer A, Hendriks HF, Roholl PJ, van Leeuwen RE, et al. Vitamin A deficiency potentiates carbon tetrachloride-induced liver fibrosis in rats. Hepatology. 1994 Jan;19(1):193-201.
15. Samoilov AV, Solovev VG, Belkina DS, Astakhova TIu, Rokina OA, Kalashnikova SP. Correction of hemostasis changes in hyperthermic exposure with antioxidant vitamin complex. V: Sikorskii AV, Khryshchanovich VIa, Gorlacheva TV, Vismont FI, red. Fundamental'naia nauka v sovremennoi meditsine – 2019: sb materialov satel distants nauch-prakt konf studentov i molodykh uchenykh, Minsk, 22 marta 2019 g. Minsk, RB; 2019. Р. 49-52. (In Russ.)
16. Volkova OV, Eletckii IuK. Basics of histology with histological technique. 2-e izd, ispr i dop. Moscow, RF: Meditsina; 1982. 304 р. (In Russ.)
17. Novogrodskaia IaI, Ostrovskaia OB, Kravchuk RI, Doroshenko EM, Guliai IE, Aleshchik AIu, i dr. A method for modeling experimental thioacetamide-induced liver damage in rats. Gepatologiia Gastroenterologiia. 2020;4(1):90-5. (In Russ.)
18. Millonig GA. Advantages of a phosphate buffer for osmium tetroxide solutions in fixation. J Appl Physics. 1961;13:1637-43.
19. Glauert AM, Glauert RH. Araldite as an embedding medium for electron microscopy. J Biophys Biochem Cytol. 1958 Mar;4(2):191-4. doi: http://dx.doi.org/10.1083/jcb.4.2.191
20. Reynolds ES. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17(1):208-12. doi: http://dx.doi.org/10.1083/jcb.17.1.208
21. Taylor SL, Lamden MP, Tappel AL. Sensitive fluorometric method for tissue tocopherol analysis. Lipids. 1976 Jul;11(7):530-8. doi: http://dx.doi.org/10.1007/BF02532898

Information about authors:
Kondratovich I.A. – lecturer of the Chair of Infectious Diseases, Grodno State Medical University,
ORCID: https://orcid.org/0000-0002-7310-5204
Andreev V.P. – Candidate of Biological Sciences, professor of the Chair of Medical Biology and Genetics, Grodno State Medical University;
Kravchuk R.I. – Candidate of Biological Sciences, senior research officer of the Research Laboratory, Grodno State Medical University;
Gulyai I.E. – Candidate of Biological Sciences, associate professor, leading research officer of the Research Laboratory, Grodno State Medical University;
Shalesnaya S.Ya. – junior research officer of the Research Laboratory, Grodno State Medical University;
Tsyrkunov V.M. – Doctor of Medical Sciences, professor of the Chair of Infectious Diseases, Grodno State Medical University,
ORCID: https://orcid.org/0000-0002-9366-6789

Correspondence address: Republic of Belarus, 230009, Grodno, 80 Gorky str., Grodno State Medical University, Chair of Infectious Diseases. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Irina A. Kondratovich.

Поиск по сайту