Study of hepatoprotective effect of bearberry leaves extract under insulin resistance in rats

Keywords: insulin resistance, diabetes mellitus type 2, hepatoprotection, bearberry, polyphenols, arginine

Abstract

The aim of our study was to evaluate the antidiabetic and hepatoprotective efficacy of dry extract from bearberry leaves enriched with arginine in dexamethasone induced IR.

Materials and methods. IR was induced in rats by low dose intraperitoneally injections of dexamethasone. Dexamethasone-induced IR in rats was treated by bearberry leaves extract enriched with arginine. Thus, animals were randomized into several groups including intact animals and animals, which administered reference compounds and medications.

The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamine transferase (GGT) were determined in blood serum and liver homogenate, in addition, in blood serum we measured lactate dehydrogenase (LDH) activity and lactate level and glycogen content liver tissue. Also, for the purpose of our experiment, in liver tissue were determined: thiobarbituric acid reactive substances (TBARS), diene conjugates (DC), and reduced glutathione (GSH) content; and superoxide dismutase (SOD), glutathione peroxidase (Gpx), and catalase (CAT) activities. All indices were determined using generally accepted unified methods or commercially available kits.

Results. Long-term dexamethasone administration led to an increase in AST, ALT and GGT overall activity in the liver homogenate and serum; this could be the result of increased permeability of hepatocyte plasma membranes, as well as their enhanced synthesis in the liver. Studied extract ameliorate these indices of liver injury. Evaluation of indices that reflected oxidative stress and the antioxidant system status in liver confirmed oxidative stress development in IR rats` liver. Administration of arginine enriched bearberry leaves extract decrease TBARS and DC content in liver tissue, at the same time, improve SOD, Gpx, and CAT activities and increase GSH content.

Conclusions. Bearberry leaves dry extract enriched with arginine inhibit oxidative stress development, improve membrane integrity, and normalize some indices of carbohydrate metabolism, particularly glycogen content in liver and lactate level in blood.

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Author Biographies

Ganna Kravchenko, National University of Pharmacy

Department of Biological Chemistry

Oksana Krasilnikova, National University of Pharmacy

Department of Biological Chemistry

References

Khan, M. A. B., Hashim, M. J., King, J. K., Govender, R. D., Mustafa, H., Al Kaabi, J. (2019). Epidemiology of Type 2 Diabetes – Global Burden of Disease and Forecasted Trends. Journal of Epidemiology and Global Health, 10 (1), 107–11. doi: http://doi.org/10.2991/jegh.k.191028.001

Jiang, S., Young, J., Wang, K., Qian, Y., Cai, L. (2020). Diabetic‑induced alterations in hepatic glucose and lipid metabolism: The role of type 1 and type 2 diabetes mellitus (Review). Molecular Medicine Reports, 22 (2), 603–611. doi: http://doi.org/10.3892/mmr.2020.11175

Hurrle, S., Hsu, W. H. (2017). The etiology of oxidative stress in insulin resistance. Biomedical Journal, 40 (5), 257–262. doi: http://doi.org/10.1016/j.bj.2017.06.007

Ormazabal, V., Nair, S., Elfeky, O., Aguayo, C., Salomon, C., Zuñiga, F. A. (2018). Association between insulin resistance and the development of cardiovascular disease. Cardiovascular Diabetology, 17 (1). doi: http://doi.org/10.1186/s12933-018-0762-4

Salehi, Ata, V. Anil Kumar, Sharopov, Ramírez-Alarcón, Ruiz-Ortega et. al. (2019). Antidiabetic Potential of Medicinal Plants and Their Active Components. Biomolecules, 9 (10), 551. doi: http://doi.org/10.3390/biom9100551

Chaika, N., Koshovyi, O., Komisarenko, M., Kireyev, I., Kravchenko, G. (2020). Standardization parameters of modified extracts from Arctostaphylos uva-ursi L. leaves. Ukrainian Biopharmaceutical Journal, 4 (65), 16–23. doi: http://doi.org/10.24959/ubphj.20.293

Koshovyi, O. M., Kravchenko, H. B., Krasilnikova, O. A., Matar, M., Chaika, N. B. (2020). Pat. No. 142210 UA. Sposib oderzhannia zasobu z hipohlikemichnoiu ta hepatoprotektornoiu diieiu z lystia muchnytsi zvychainoi z dodavanniam arhininu. MPK: A61K 36/45 (2006.01), A61P 3/10 (2006.01). No. u201910482; declareted: 21.10.2019; published: 25.05.2020, Bul. No. 10.

Modyfikatsiia metodu modeliuvannia eksperymentalnoi insulinorezystentosti u shchuriv: inform. lyst No. 86-2015 Ukrmedpatentinformu pro novovvedennia v systemi okhorony zdorovia (2015). Kyiv, 3.

Templeton, M. (1961). Microdetermination of glycogen with anthrone reagent. Journal of Histochemistry & Cytochemistry, 9 (6), 670–672. doi: http://doi.org/10.1177/9.6.670

Buege, J. A., Aust, S. D. (1978). Microsomal lipid peroxidation. Methods of Enzymology, 52, 302–310. doi: http://doi.org/10.1016/s0076-6879(78)52032-6

Peg, R. J. (2001). Determination of conjugated dienes and trienes. Current Protocols in Food Analytical Chemistry. New York: John Wiley & Sons, D2.1.1–D2.1.3.

Moron, M., Depierre, J., Mannervik, B. (1979). Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochimica et Biophysica Acta (BBA) – General Subjects, 582 (1), 67–78. doi: http://doi.org/10.1016/0304-4165(79)90289-7

McCord, J. M., Fridovich, I. (1969). Superoxide Dismutase. Journal of Biological Chemistry, 244 (22), 6049–6055. doi: http://doi.org/10.1016/s0021-9258(18)63504-5

Hafeman, D. G., Sunde, R. A., Hoekstra, W. G. (1974). Effect of Dietary Selenium on Erythrocyte and Liver Glutathione Peroxidase in the Rat. The Journal of Nutrition, 104 (5), 580–587. doi: http://doi.org/10.1093/jn/104.5.580

Tenovuo, J., Pruitt, K. M., Mansson-Rahemtulla, B., Harrington, P., & Baldone, D. C. (1986). Products of thiocyanate peroxidation: properties and reaction mechanisms. Biochimica et Biophysica Acta (BBA) – Protein Structure and Molecular Enzymology, 870 (3), 377–384. doi: http://doi.org/10.1016/0167-4838(86)90244-x

Miller, G. L. (1959). Protein Determination of Large Numbers of Samples. Analytical Chemistry, 31 (5), 964–966. doi: http://doi.org/10.1021/ac60149a611

Kravchenko, G. B., Krasilnikova, O. A., Mazen, M. (2020). Hypoglycemic and hypolipidemic activity of arginine containing bearberry leaves extract in insulin resistant rats. Medical and Clinical Chemistry, 1, 5–10. doi: http://doi.org/10.11603/mcch.2410-681x.2020.v.i1.10936

Petersen, M. C., Vatner, D. F., Shulman, G. I. (2017). Regulation of hepatic glucose metabolism in health and disease. Nature Reviews Endocrinology, 13 (10), 572–587. doi: http://doi.org/10.1038/nrendo.2017.80

Ishitobi, M., Hosaka, T., Morita, N., Kondo, K., Murashima, T., Kitahara, A. et. al. (2019). Serum lactate levels are associated with serum alanine aminotransferase and total bilirubin levels in patients with type 2 diabetes mellitus: A cross-sectional study. Diabetes Research and Clinical Practice, 149, 1–8. doi: http://doi.org/10.1016/j.diabres.2019.01.028

Yazdi, H. B., Hojati, V., Shiravi, A., Hosseinian, S., Vaezi, G., Hadjzadeh, M. A. (2019). Liver Dysfunction and Oxidative Stress in Streptozotocin-Induced Diabetic Rats: Protective Role of Artemisia Turanica. Journal of Pharmacopuncture, 22 (2), 109–114. doi: http://doi.org/10.3831/KPI.2019.22.014

Zhu, L., Yi, X., Zhao, J., Yuan, Z., Wen, L., Pozniak, B. et. al. (2018). Betulinic acid attenuates dexamethasone-induced oxidative damage through the JNK-P38 MAPK signaling pathway in mice. Biomedicine & Pharmacotherapy, 103, 499–508. doi: http://doi.org/10.1016/j.biopha.2018.04.073

Safhi, M. M., Alam, M. F., Sivakumar, S. M., Anwer, T. (2019). Hepatoprotective Potential ofSargassum muticumagainst STZ-Induced Diabetic Liver Damage in Wistar Rats by Inhibiting Cytokines and the Apoptosis Pathway. Analytical Cellular Pathology, 2019, 1–8. doi: http://doi.org/10.1155/2019/7958701

Gothandam, K., Ganesan, V. S., Ayyasamy, T., Ramalingam, S. (2019). Antioxidant potential of theaflavin ameliorates the activities of key enzymes of glucose metabolism in high fat diet and streptozotocin – induced diabetic rats. Redox Report, 24 (1), 41–50. doi: http://doi.org/10.1080/13510002.2019.1624085

Song, X.-C., Canellas, E., Asensio, E., Nerín, C. (2020). Predicting the antioxidant capacity and total phenolic content of bearberry leaves by data fusion of UV–Vis spectroscopy and UHPLC/Q-TOF-MS. Talanta, 213, 120831. doi: http://doi.org/10.1016/j.talanta.2020.120831

Liang, H., Ji, K., Ge, X., Ren, M., Liu, B., Xi, B., Pan, L. (2018). Effects of dietary arginine on antioxidant status and immunity involved in AMPK-NO signaling pathway in juvenile blunt snout bream. Fish & Shellfish Immunology, 78, 69–78. doi: http://doi.org/10.1016/j.fsi.2018.04.028

Zhang, Y., Zhang, J., Wang, E., Qian, W., Fan, Y., Feng, Y. et. al. (2018). Microcystin-Leucine-Arginine Induces Tau Pathology Through Bα Degradation via Protein Phosphatase 2A Demethylation and Associated Glycogen Synthase Kinase-3β Phosphorylation. Toxicological Sciences, 162 (2), 475–487. doi: http://doi.org/10.1093/toxsci/kfx271

Hollyer, T. R., Bordoni, L., Kousholt, B. S., Luijk, J., Ritskes‐Hoitinga, M., Østergaard, L. (2019). The evidence for the physiological effects of lactate on the cerebral microcirculation: a systematic review. Journal of Neurochemistry, 148 (6), 712–730. doi: http://doi.org/10.1111/jnc.14633


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Published
2021-11-30
How to Cite
Mazen, M., Kravchenko, G., & Krasilnikova, O. (2021). Study of hepatoprotective effect of bearberry leaves extract under insulin resistance in rats. EUREKA: Health Sciences, (6), 48-53. https://doi.org/10.21303/2504-5679.2021.002174
Section
Pharmacology, Toxicology and Pharmaceutical Science