Effect of liposomal drug based on interferon and extract from Silybum marianum on antioxidative status of bulls against the background of contamination of fodders by cadmium and plumbum

  • B. V. Gutyj Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies
  • T. V. Martyshuk Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies
  • V. V. Parchenko Zaporizhzhia State Medical University
  • A. H. Kaplaushenko Zaporizhzhia State Medical University
  • I. V. Bushueva Zaporizhzhia State Medical University
  • I. I. Hariv Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies
  • Y. P. Bilash Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies
  • V. V. Brygadyrenko Oles Honchar Dnipro National University
  • Y. I. Turko Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies
  • M. L. Radzykhovskyi National University of Life and Environmental Sciences of Ukraine
Keywords: heavy metals; glutathione system, catalase; superoxide dismutase; diene conjugates; liposomes


The balance between anti- and prooxidants in animal organisms in general and in each cell in particular is responsible for the regulation of many metabolic processes that provide immunocompetence, growth, development and protection of animals from oxidative stress, related to inflow of cadmium and plumbum. Therefore, the objective of our study was the influence of a liposomal drug based on interferon and milk thistle (Silybum marianum (L.) Gaertn.) on the antioxidative status of the organism of bulls in the conditions of cadmium and plumbum loading. The experiments were performed on six-months-old Black Motley dairy cattle. The fodders in the farm were determined to contain high levels of plumbum and cadmium. The liposomal drug Lipointersyl inhibited the lipid peroxidation processes in the bulls. The drug components promoted the decrease in the level of intermediate and end products of lipid peroxidation, in particular 22% decrease in the level of diene conjugates and 20% decrease in TBA-active products. Intramuscular injection of the liposomal drug to bulls of the experimental group strengthened the antioxidant protection of their organism. On the 30th day of the experiment, blood from experimental group animals was seen to have a 9.8% increase in reduced glutathione. Assay of the enzymatic link of the glutathione system revealed that the activity of glutathione peroxidase and glutathione reductase in the blood of the animals that had been injected the liposomal drug Lipointensyl had increased by 24.0% and 27.7% respectively by the 30th day of the experiment. The experiments conducted on young cattle demonstrated that intermuscularly injected the Lipointensyl liposomal drug – against the background of cadmium and plumbum loading – promoted the activation of the glutathione system of antioxidant protection as a result of increase in the activity of its enzymatic and non-enzymatic links. The study of catalase and superoxide dismutase activities revealed that on the 30th and 40th days of the experiment, the activity of those enzymes varied within the physiological norms. Therefore, the analyzed Silybum marianum-based liposomal drug has antioxidant properties, it is recommended for young cattle in the conditions of contamination with heavy metals in order to prevent the development of oxidative stress.


Abbasi, H., Rahbar, N., Kouchak, M., Khalil Dezfuli, P., & Handali, S. (2022). Functionalized liposomes as drug nanocarriers for active targeted cancer therapy: A systematic review. Journal of Liposome Research, 32(2), 195–210.

Akter, M. T., Ferdous, K. A., Rahaman, T., Hassan, M. A., & Monjur, T. (2019). Exposure to environmental heavy metal (cadmium) through feed and its effect on bio-histomorphological changes in commercial quail. Journal of Entomology and Zoology Studies, 7, 965–971.

Bashchenko, M. I., Boiko, О. V., Honchar, О. F., Gutyj, B. V., Lesyk, Y. V., Ostapyuk, A. Y., Kovalchuk, І. І., & Leskiv, K. Y. (2020). The effect of milk thistle, metiphen, and silimevit on the protein-synthesizing function of the liver of laying hens in experimental chronic cadmium toxicosis. Ukrainian Journal of Ecology, 10(6), 164–168.

Bomko, V., Kropyvka, Y., Bomko, L., Chernyuk, S., Kropyvka, S., & Gutyj, B. (2018). Effect of mixed ligand complexes of zinc, manganese, and cobalt on the manganese balance in high-yielding cows during first 100-days lactation. Ukrainian Journal of Ecology, 8(1), 420–425.

Bono, S., Feligioni, M., & Corbo, M. (2021). Impaired antioxidant KEAP1-NRF2 system in amyotrophic lateral sclerosis: NRF2 activation as a potential therapeutic strategy. Molecular Neurodegeneration, 16(1), 71.

Borisenko, N. N., Bushueva, I. V., Parchenko, V. V., Gubenko, I. Y., Mykhailiuk, Y. О., Riznyk, O. I., Aleksieiev, O. G., Gutyj, B. V., Lysianska, H. P., & Kurinnyi, A. V. (2019). Anti-inflammatory, antiviral veterinary medicine with immuno-modulating activity. Research Journal of Pharmacy and Technology, 12(11), 5455–5459.

Boyko, O. O., & Brygadyrenko, V. V. (2019). Nematocidial activity of aqueous solutions of plants of the families Cupressaceae, Rosaceae, Asteraceae, Fabaceae, Cannabaceae and Apiaceae. Biosystems Diversity, 27(3), 227–232.

Dang, X., Cho, S., & Kim, I. H. (2022). Silybum marianum seed extract supplementation positively affects the body weight of weaned piglets by improving voluntary feed intake. Journal of Animal Science and Technology, 64(4), 696–706.

De Leo, V., Maurelli, A. M., Giotta, L., & Catucci, L. (2022). Liposomes containing nanoparticles: Preparation and applications. Colloids and Surfaces B: Biointerfaces, 218, 112737.

Dyachenko, L., Syvyk, T., & Kosyanenko, О. (2015). Influence of different levels of cadmium in ration with natural detoxicant on performance, digestibility of substances and metabolism of nitrogen in young fattening pigs. Tekhnolohiia Vyrobnytstva i Pererobky Produktsii Tvarynnytstva, 1, 163–168.

Eita, A. A. B. (2022). Milk thistle (Silybum marianum (L.) Gaertn.): An overview about its pharmacology and medicinal uses with an emphasis on oral diseases. Journal of Oral Biosciences, 64(1), 71–76.

Ferro, J. P., Ferrari, L., & Eissa, B. L. (2021). Acute toxicity of cadmium to freshwater fishes and its relationship with body size and respiratory strategy. Comparative Biochemistry and Physiology, Part C: Toxicology and Pharmacology, 248, 109109.

Gul, I., Manzoor, M., Hashim, N., Shah, G. M., Waani, S. P. T., Shahid, M., Antoniadis, V., Rinklebe, J., & Arshad, M. (2021). Challenges in microbially and chelate-assisted phytoextraction of cadmium and lead – A review. Environmental Pollution, 287, 117667.

Gutyi, B., Ostapiuk, A., Kachmar, N., Stadnytska, O., Sobolev, O., Binkevych, V., Petryshak, R., Petryshak, O., Kulyaba, O., Naumyuk, A., Nedashkivsky, V., Nedashkivska, N., Magrelo, N., Golodyuk, I., Nazaruk, N., & Binkevych, O. (2019). The effect of cadmium loading on protein synthesis function and functional state of laying hens’ liver. Ukrainian Journal of Ecology, 9(3), 222–226.

Gutyj, B. V., Ostapyuk, A. Y., Sobolev, O. I., Vishchur, V. J., Gubash, O. P., Kurtyak, B. M., Kovalskyi, Y. V., Darmohray, L. M., Hunchak, A. V., Tsisaryk, O. Y., Shcherbatyy, A. R., Farionik, T. V., Savchuk, L. B., Palyadichuk, O. R., & Hrymak, K. (2019). Cadmium burden impact on morphological and biochemical blood indicators of poultry. Ukrainian Journal of Ecology, 9(1), 235–239.

Gutyj, B., Stybel, V., Darmohray, L., Lavryshyn, Y., Turko, I., Hachak, Y., Shcherbatyy, A., Bushueva, I., Parchenko, V., Kaplaushenko, A., & Krushelnytska, O. (2017). Prooxidant-antioxidant balance in the organism of bulls (young cattle) after using cadmium load. Ukrainian Journal of Ecology, 7(4), 589–596.

Hong, Y., Chen, Y., Shen, R., Chen, S., Xu, G., Cheng, H., Guo, L., Wei, Z., Yang, J., Liu, Y., Shi, Z., & Mouazen, A. M. (2021). Diagnosis of cadmium contamination in urban and suburban soils using visible-to-near-infrared spectroscopy. Environmental Pollution, 291, 118128.

Hui, C. Y., Guo, Y., Liu, L., & Yi, J. (2021). Recent advances in bacterial biosensing and bioremediation of cadmium pollution: A mini-review. World Journal of Microbiology and Biotechnology, 38(1), 9.

Kailasam, S., & Peiter, E. (2021). A path toward concurrent biofortification and cadmium mitigation in plant-based foods. New Phytologist Foundation, 232(1), 17–24.

Kar, I., & Patra, A. K. (2021). Tissue bioaccumulation and toxicopathological effects of cadmium and its dietary amelioration in poultry – a review. Biological Trace Element Research, 199(10), 3846–3868.

Karpenko, Y., Hunchak, Y., Gutyj, B., Hunchak, A., Parchenko, M., & Parchenko, V. (2022). Advanced research for physico-chemical properties and parameters of toxicity piperazinium 2-((5-(furan-2-YL)-4-phenyl-4H-1,2,4-triazol-3-yl) thio)acetate. ScienceRise: Pharmaceutical Science, 36, 18–25.

Khariv, M., Gutyj, B., Ohorodnyk, N., Vishchur, O., Khariv, I., Solovodzinska, I., Mudrak, D., Grymak, C., & Bodnar, P. (2017). Activity of the T- and B-system of the cell immunity of animals under conditions of oxidation stress and effects of the liposomal drug. Ukrainian Journal of Ecology, 7(4), 536–541.

Khazaei, R., Seidavi, A., & Bouyeh, M. (2022). A review on the mechanisms of the effect of silymarin in milk thistle (Silybum marianum) on some laboratory animals. Veterinary Medicine and Science, 8(1), 289–301.

Kowalczyk, P., Sulejczak, D., Kleczkowska, P., Bukowska-Ośko, I., Kucia, M., Popiel, M., Wietrak, E., Kramkowski, K., Wrzosek, K., & Kaczyńska, K. (2021). Mitochondrial oxidative stress – a causative factor and therapeutic target in many diseases. International Journal of Molecular Sciences, 22(24), 13384.

Lavryshyn, Y. Y., Gutyj, B. V., Leskiv, K. Y., Hariv, I. I., Yevtukh, L. H., & Shnaider, V. L. (2020). Influence of cadmium on the cellular part of the immune system of young cattle. Ukrainian Journal of Veterinary and Agricultural Sciences, 3(2), 47–52.

Martyshuk, T. V., Gutyj, B. V., Zhelavskyi, M. M., Midyk, S. V., Fedorchenko, A. M., Todoriuk, V. B., Nahirniak, T. B., Kisera, Y. V., Sus, H. V., Chemerys, V. A., Levkivska, N. D., & Iglitskej, I. I. (2020). Effect of Butaselmevit-Plus on the immune system of piglets during and after weaning. Ukrainian Journal of Ecology, 10(2), 347–352.

Martyshuk, T., Gutyj, B., Vyshchur, O., Paterega, I., Kushnir, V., & Bigdan, O. (2022). Study of acute and chronic toxicity of “Butaselmevit” on laboratory animals. Archives of Pharmacy Practice, 13(3), 70–75.

Mylostyvyi, R., Lesnovskay, O., Karlova, L., Khmeleva, O., Кalinichenko, O., Orishchuk, O., Tsap, S., Begma, N., Cherniy, N., Gutyj, B., & Izhboldina, O. (2021). Brown Swiss cows are more heat resistant than Holstein cows under hot summer conditions of the continental climate of Ukraine. Journal of Animal Behaviour and Biometeorology, 9(4), 2134.

Mylostyvyi, R., Sejian, V., Izhboldina, O., Kalinichenko, O., Karlova, L., Lesnovskay, O., Begma, N., Marenkov, O., Lykhach, V., Midyk, S., Cherniy, N., Gutyj, B., & Hoffmann, G. (2021). Changes in the spectrum of free fatty acids in blood serum of dairy cows during a prolonged summer heat wave. Animals, 11(12), 3391.

Nordberg, M., & Nordberg, G. F. (2022). Metallothionein and cadmium toxicology – historical review and commentary. Biomolecules, 12(3), 360.

Ozturk, M., Metin, M., Altay, V., De Filippis, L., Ünal, B. T., Khursheed, A., Gul, A., Hasanuzzaman, M., Nahar, K., Kawano, T., & Caparrós, P. G. (2021). Molecular biology of cadmium toxicity in Saccharomyces cerevisiae. Biological Trace Element Research, 199(12), 4832–4846.

Palchykov, V. A., Zazharskyi, V. V., Brygadyrenko, V. V., Davydenko, P. O., Kulishenko, O. M., Borovik, I. V., Chumak, V., Kryvaya, A., & Boyko, O. O. (2019). Bactericidal, protistocidal, nematodicidal properties and chemical composition of ethanol extract of Punica granatum peel. Biosystems Diversity, 27(3), 300–306.

Razanova, O., Yaremchuk, O., Gutyj, B., Farionik, T., & Novgorodska, N. (2022). Dynamics of some mineral elements content in the muscle, bone and liver of quails under the apimin influence. Scientific Horizons, 25(5), 22–29.

Rezapour, M., Rezapour, H. A., Chegeni, M., & Khanjani, N. (2021). Exposure to cadmium and head and neck cancers: A meta-analysis of observational studies. Reviews on Environmental Health, 36(4), 577–584.

Sameliuk, Y., Kaplaushenko, A., Nedorezanıuk, N., Ostretsova, L., Diakova, F., & Gutyj, B. (2022). Prospects for the search for new biologically active compounds among the derivatives of the heterocyclic system of 1,2,4-triazole. Hacettepe University Journal of the Faculty of Pharmacy, 42(3), 175–186.

Shahid, A., Khan, M. M., Ahmad, U., Haider, M. F., & Ali, A. (2022). Exploring liposomes for lung cancer therapy. Critical Reviews in Therapeutic Drug Carrier Systems, 39(4), 1–47.

Shehzad, M. A., Khan, M. A., Ali, A., Mohammad, S., Noureldeen, A., Darwish, H., Ali, A., Ahmad, A., Khan, T., & Khan, R. S. (2021). Interactive effects of zinc oxide nano particles and different light regimes on growth and silymarin biosynthesis in callus cultures of Silybum marianum L. Artificial Cells, Nanomedicine, and Biotechnology, 49(1), 523–535.

Shiyntum, H. N., & Ushakovа, G. A. (2015). Protective/detoxicative function of metallothionein in the rat brain and blood induced by controlled cadmium doses. Visnyk of Dnipropetrovsk University, Biology, Medicine, 6(2), 103–107.

Skliarov, P., Kornienko, V., Midyk, S., & Mylostyvyi, R. (2022). Impaired reproductive performance of dairy cows under heat stress. Agriculturae Conspectus Scientificus, 87(2), 85–92.

Slivinska, L. G., Shcherbatyy, A. R., Lukashchuk, B. O., Zinko, H. O., Gutyj, B. V., Lychuk, M. G., Chernushkin, B. O., Leno, M. I., Prystupa, O. I., Leskiv, K. Y., Slepokura, O. I., Sobolev, O. I., Shkromada, O. I., Kysterna, O. S., & Мusiienko, O. V. (2019). Correction of indicators of erythrocytopoesis and microelement blood levels in cows under conditions of technogenic pollution. Ukrainian Journal of Ecology, 9(2), 127–135.

Slobodian, S. О., Gutyj, B. V., & Leskiv, K. Y. (2019). The level of lipid peroxidation products in the rats blood under prolonged cadmium and lead loading. Ukrainian Journal of Veterinary and Agricultural Sciences, 2(3), 15–18.

Tajmohammadi, A., Razavi, B. M., & Hosseinzadeh, H. (2018). Silybum marianum (milk thistle) and its main constituent, silymarin, as a potential therapeutic plant in metabolic syndrome: A review. Phytotherapy Research, 32(10), 1933–1949.

Tsekhmistrenko, O., & Tsekhmistrenko, S. (2015). Lipid peroxidation in the quail’s kidney under cadmium load and Sel-Plex influence. Tekhnolohiia Vyrobnytstva i Pererobky Produktsii Tvarynnytstva, 1, 203–207.

Vaid, M., & Katiyar, S. K. (2010). Molecular mechanisms of inhibition of photocarcinogenesis by silymarin, a phytochemical from milk thistle (Silybum marianum L. Gaertn.) (Review). International Journal of Oncology, 36(5), 1053–1060.

Vishchur, V. Y., Gutyj, B. V., Nischemenko, N. P., Kushnir, I. M., Salata, V. Z., Tarasenko, L. O., Khimych, M. S., Kushnir, V. I., Kalyn, B. M., Magrelo, N. V., Boiko, P. K., Kolotnytskyy, V. A., Velesyk, T., Pundyak, T. O., Gubash, O. P. (2019). Effect of industry on the content of fatty acids in the tissues of the honey-bee head. Ukrainian Journal of Ecology, 9(3), 174–179.

Wang, L., Tang, J., Wang, L., Tan, F., Song, H., Zhou, J., & Li, F. (2021). Oxidative stress in oocyte aging and female reproduction. Journal of Cellular Physiology, 236(12), 7966–7983.

Wu, J., Li, R., Lu, Y., & Bai, Z. (2021). Sustainable management of cadmium-contaminated soils as affected by exogenous application of nutrients: A review. Journal of Environmental Management, 295, 113081.

Yassin, N. Y. S., AbouZid, S. F., El-Kalaawy, A. M., Ali, T. M., Elesawy, B. H., & Ahmed, O. M. (2021). Tackling of renal carcinogenesis in Wistar rats by Silybum marianum total extract, silymarin, and silibinin via modulation of oxidative stress, apoptosis, Nrf2, PPARγ, NF-κB, and PI3K/Akt signaling pathways. Oxidative Medicine and Cellular Longevity, 2021, 7665169.

Zazharska, N., Boyko, O., & Brygadyrenko, V. (2018). Influence of diet on the productivity and characteristics of goat milk. Indian Journal of Animal Research, 52(5), 711–717.

Zazharskyi, V. V., Davydenko, P. О., Kulishenko, O. М., Borovik, I. V., & Brygadyrenko, V. V. (2019). Antimicrobial activity of 50 plant extracts. Biosystems Diversity, 27(2), 163–169.

Zazharskyi, V. V., Davydenko, P. О., Kulishenko, O. М., Borovik, I. V., Zazharska, N. M., & Brygadyrenko, V. V. (2020). Antibacterial and fungicidal activities of ethanol extracts of 38 species of plants. Biosystems Diversity, 28(3), 281–289.

Zazharskyi, V., Davydenko, P., Kulishenko, O., Borovik, I., Brygadyrenko, V., & Zazharska, N. (2019). Antibacterial activity of herbal infusions against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa in vitro. Magy Állatorvosok Lapja, 141, 693–704.

Zeng, L., Zhou, J., Wang, X., Zhang, Y., Wang, M., & Su, P. (2021). Cadmium attenuates testosterone synthesis by promoting ferroptosis and blocking autophagosome-lysosome fusion. Free Radical Biology and Medicine, 176, 176–188.

Zhang, X., Zhang, P., Hu, Y., Liu, Y., Feng, S., Guo, D., & Dang, X. (2021). Immobilization of cadmium in soil and improved iron concentration and grain yields of maize (Zea mays L.) by chelated iron amendments. Environmental Science and Pollution Research, 28(38), 53161–53170.

Zhao, C., Yu, D., He, Z., Bao, L., Feng, L., Chen, L., Liu, Z., Hu, X., Zhang, N., Wang, T., & Fu, Y. (2021). Endoplasmic reticulum stress-mediated autophagy activation is involved in cadmium-induced ferroptosis of renal tubular epithelial cells. Free Radical Biology and Medicine, 175, 236–248.

Zheng, Y., Xiao, C., & Chi, R. (2021). Remediation of soil cadmium pollution by biomineralization using microbial-induced precipitation: A review. World Journal of Microbiology and Biotechnology, 37(12), 208

How to Cite
Gutyj, B. V., Martyshuk, T. V., Parchenko, V. V., Kaplaushenko, A. H., Bushueva, I. V., Hariv, I. I., Bilash, Y. P., Brygadyrenko, V. V., Turko, Y. I., & Radzykhovskyi, M. L. (2022). Effect of liposomal drug based on interferon and extract from Silybum marianum on antioxidative status of bulls against the background of contamination of fodders by cadmium and plumbum . Regulatory Mechanisms in Biosystems, 13(4), 419-425. https://doi.org/10.15421/022255

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