Toxicological assessment of a bioactive adaptogenic drug for use in rats and pigs

  • I. Korkh Livestock Farming Institute of the National Academy of Agrarian Sciences of Ukraine
  • Y. Koreneva National Scientific Center "Institute of Experimental and Clinical Veterinary Medicine"
  • V. Boiko National Scientific Center "Institute of Experimental and Clinical Veterinary Medicine"
  • I. Gerilovych National Scientific Center "Institute of Experimental and Clinical Veterinary Medicine"
  • O. Korkh Livestock Farming Institute of the National Academy of Agrarian Sciences of Ukraine
  • L. Kovalenko National Scientific Center "Institute of Experimental and Clinical Veterinary Medicine"
  • A. Paliy National Scientific Center "Institute of Experimental and Clinical Veterinary Medicine"
  • N. Boiko Livestock Farming Institute of the National Academy of Agrarian Sciences of Ukraine
  • L. Kovalenko Sumy National Agrarian University
  • Y. Livoshchenko Sumy National Agrarian University
Keywords: adaptogenic drug, glycine, succinic acid, biologically active medium 199, internal organ mass index, hematological blood parameters, stress resistance in male piglets.

Abstract

Glycine and succinic acid elicit a potent stress response. They are not just anti-stress agents; they form a highly effective bioregulatory complex that quickly mobilizes animals' adaptive reserves and significantly reduces the impact of environmental stressors. Their synergistic action achieves a new level of effectiveness when combined with bioactive substances that enhance their physiological effects. The primary focus in this context is the development of a multicomponent adaptogenic drug based on glycine, succinic acid, and a biologically active medium 199, and its toxicological evaluation in rats and pigs. It has been esta b lished that a single intragastric administration of the bioactive adaptogenic preparation to male rats at doses of 1000 and 3000 mg/kg body weight did not result in any adverse effects on their clinical condition. Administering a dose of 5000 mg/kg of body weight was accompanied by a transient decrease in motor activity during the first two days after administration. When 9000 and 10000 mg/kg doses were applied to the skin of female rats, mild erythema was observed and disappeared within two hours. Field testing of the therapeutic dose (1.5 mL) demonstrated the drug's high efficacy in rapidly restoring behavioral responses, reducing stress levels, and normalizing physiological parameters in boars after castration. A pathological examination revealed no significant changes in the internal organs except for a probable increase in spleen mass index in female rat s that received 2.0 mL on the tenth day, likely due to increased sensitivity to the drug. Rats that received a 1.5 mL dose of the drug demonstrated i n creased hemoglobin, red blood cell, and total protein levels, as well as lower glucose levels. This is a characteristic manifestation of better adaptation to stressful conditions. Overall, the drug is classified as practically non-toxic in terms of toxicity and as low-toxicity in terms of hazard level. This study will further evaluate adaptogenic anti-stress drugs in mitigating the negative effects of technological stressors on pigs at various stages of the rearing cycle.

References

Ayo, J. O., Minka, N. S., & Mamman, M. (2006). Excitability scores of goats administered ascorbic acid and transported during hot-dry conditions. Journal of Veterinary Science, 7(2), 127–131.

Beydoun, H. A., Beydoun, M. A., Wassertheil-Smoller, S., Saquib, N., Manson, J. E., Snetselaar, L., Weiss, J., Zonderman, A. B., & Brunner, R. (2024). Depressive symptoms and antidepressant use in relation to white blood cell count among postmenopausal women from the Women's Health Initiative. Translational Psychiatry, 14(1), 157–170.

Bi, C., Yin, J., Yang, W., Shi, B., & Shan, A. (2020). Effects of dietary γ-aminobutyric acid supplementation on antioxidant status, blood hormones and meat quality in growing-finishing pigs undergoing transport stress. Journal of Animal Physiology and Animal Nutrition, 104(2), 590–596.

Bova, T. L., Chiavaccini, L., Cline, G. F., Hart, C. G., Matheny, K., Muth, A. M., Voelz, B. E., Kesler, D., & Memili, E. (2014). Environmental stressors influencing hormones and systems physiology in cattle. Reproductive Biology and Endocrinology, 12(1), 58–62.

Chalasani, N. P., Maddur, H., Russo, M. W., Wong, R. J., & Reddy, K. R. (2021). ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. American Journal of Gastroenterology, 116(5), 878–898.

Chen, Y., Guo, Dj., Deng, H., Wu, M. F., Zhang, Y. N., Li, S., Xu, R., Chen, J., Jin, X. X., Li, B., Xu, Q., & Li, F. L. (2018). Acute and chronic toxicity of a polyherbal preparation – Jueyin granules. Complementary and Alternative Medicine, 18(1), e148.

Decker, R., von Stuckrad-Barre, S., Milakofsky, L., Hofford, J. M., Harris, N., & Vogel, W. H. (1995). Effect of stress on amino acids and related compounds in various tissues of the rat. Life Sciences, 57(19), 1781–1790.

Dragoş, D., & Tănăsescu, M. D. (2010). The effect of stress on the defense systems. Journal of Medicine and Life, 3(1), 10–18.

Engel, J., Haack, B., Zolk, O., Greiner, T., Heinze, M., Toto, S., Seifert, J., Bleich, S., Glocker, C., Grohmann, R., Schneider, M., & Stübner, S. (2024). Edema related to treatment with psychotropic drugs. Journal of Neural Transmission, 131(3), 253–266.

Geetanjali, G., Wahane, A., & Sharma, A. (2023). Exploring effective strategies for stress management: Enhancing mental well-being through mindfulness, CBT, exercise, and relaxation techniques. Bulletin of Indonesian Economic Studies, 12(5), 345–348.

Gonzalez-Rivas, P. A., Chauhan, S. S., Ha, M., Fegan, N., Dunshea, F. R., & Warner, R. D. (2020). Effects of heat stress on animal physiology, metabolism, and meat quality: A review. Meat Science, 162, e108025.

Hussain, H., Ahmad, S., Shah, S. W. A., Ullah, A., Almehmadi, M., Abdulaziz, O., Allahyani, M., Alsaiari, A. A., Halawi, M., & Alamer, E. (2022). Investigation of anti-stress and antidepressant activities of synthetic curcumin analogues: behavioral and biomarker approach. Biomedicines, 10(10), e2385.

Intatham, S., Taychaworaditsakul, W., Khonsung, P., Chansakaow, S., Jaijoy, K., Lertprasertsuke, N., Soonthornchareonnon, N., & Sireeratawong, S. (2024). Safety evaluation for acute and chronic oral toxicity of Maha Pigut Triphala contains three medicinal fruits in Sprague-Dawley Rats. Biology, 13(12), e1005.

Korkh, I. V., Boiko, N. V., Pomitun, І. A., Paliy, A. P., Pavlichenko, O. V., Negreba, Y. V., Rysovanyi, V. I., & Siabro, A. S. (2023). The impact of environmental temperature on ewe reproduction, adaptive responses during insemination, and productive characteristics of the lambs obtained from them. Regulatory Mechanisms in Biosystems, 14(3), 358–364.

Korkh, I. V., Lashyn, D. A., Boiko, N. V., Paliy, A. P., Akimov, O. V., Pavlichenko, O. V., Borovkov, S. B. & Palii, N. V. (2025). Formation of the functional state of piglets' organisms in response to stress induced by weaning from the sow. Fiziologichnyi Zhurnal, 71(6), 85–94.

Kovalenko, L. V., Paliy, А. P., Kornieikov, O. M., Belikov, K. M., & Bryleva, K. Y. (2024). Toxicological properties of mixtures of binary silver-copper, silver-zinc, and copper nanoparticles on cell culture model and laboratory animals. Regulatory Mechanisms in Biosystems, 15(3), 552–560.

Li, S., Tan, H. Y., Wang, N., Zhang, Z. J., Lao, L., Wong, C. W., & Feng, Y. (2015). The role of oxidative stress and antioxidants in liver diseases. International Journal of Molecular Sciences, 16(11), 26087–26124.

Liu, F., Zhao, W., Le, H. H., Cottrell, J. J., Green, M. P., Leury, B. J., Dunshea, F. R., & Bell, A. W. (2022). Review: What have we learned about the effects of heat stress on the pig industry? Animal, 16(2), e100349.

Lynall, M. E., Turner, L., Bhatti, J., Cavanagh, J., de Boer, P., Mondelli, V., Jones, D., Drevets, W. C., Cowen, P., Harrison, N. A., Pariante, C. M., Pointon, L., Clatworthy, M. R., Bullmore, E., & Neuroimmunology of mood disorders and alzheimer’s disease (NIMA) consortium (2020). Peripheral blood cell-stratified subgroups of inflamed depression. Biological Psychiatry, 88(2), 185–196.

Martínez-Miró, S., Tecles, F., Ramón, M., Escribano, D., Hernández, F., Madrid, J., Orengo, J., Martínez-Subiela, S., Manteca, X., & Cerón, J. J. (2016). Causes, consequences and biomarkers of stress in swine: An update. BMC Veterinary Research, 12(1), 171–179.

Nielsen, S. S., Alvarez, J., Bicout, D. J., Calistri, P., Canali, E., Drewe, J. A., Garin-Bastuji, B., Gonzales Rojas, J. L., Schmidt, C. G., Michel, V., Miranda Chueca, M. Á., Padalino, B., Pasquali, P., Roberts, H. C., Spoolder, H., Stahl, K., Velarde, A., Viltrop, A., Winckler, C., Earley, B., Edwards, S., Faucitano, L., Marti, S., de La Lama, G. C. M., Costa, L. N., Thomsen, P. T., Ashe, S., Mur, L., Van der Stede, Y., & Herskin, M. (2022). Welfare of pigs during transport. EFSA Journal, 20(9), e7445.

Obeagu, E. I. (2025). Stress, neutrophils, and immunity: a dynamic interplay. Annals of Medicine and Surgery, 87(6), 3573–3585.

Paliy, A. P., Kovalenko, L. V., Rodionova, K. O., Pavlichenko, O. V., Кhimych, M. S., & Balta, M. P. (2024). Pathomorphological changes in laboratory animals exposed to lethal doses of disinfectants. Regulatory Mechanisms in Biosystems, 15(1), 107–112.

Pillinger, T., Arumuham, A., McCutcheon, R. A., D'Ambrosio, E., Basdanis, G., Branco M., Carr, R., Finelli, V., Furukawa, T. A., Gee, S., Heald, A., Jauhar, S. Ma, Z., Mancini, V., Moulton, C., Salanti, D., Taylor, M., Tomlinson, A., Young, A. H., Efthimiou, O., Howes, O. D., & Cipriani, A. (2025). The effects of antidepressants on cardiometabolic and other physiological parameters: A systematic review and network meta-analysis. The Lancet, 406(10515), 2063–2077.

Poroshinska, O., Polishchuk, A., Shmayun, S., Kozii, N., Shahanenko, R., Chornozub, M., Stovbetska, L., Shahanenko, V., & Koziy, V. (2024). The use of anxiolytic drugs for the correction of behavioral disorders in mammals. Regulatory Mechanisms in Biosystems, 15(1), 42–48.

Puangsri, P., Jinanarong, V., & Ninla-Aesong, P. (2023). Impact of antidepressant treatment on complete blood count parameters and inflammatory ratios in adolescents with major depressive disorder. Journal of Psychiatric Research, 157, 26–35.

Rodrigues, A., Beresford, L., Scudamore, C. L., & Yon, M. (2022). A guide to post-mortem examination procedure in mouse models. Laboratory Animals, 56(5), 466–470.

Santi, N., Biswal, S. B., Naik, B., Sahoo, J. P., & Rath, B. (2023). Metabolic effects of antidepressants: Results of a randomized study’s interim analysis. Cureus, 15(7), e42585.

Sealock, J. M., Chen, G., & Davis, L. K. (2023). Anti-inflammatory action of antidepressants: Investigating the longitudinal effect of antidepressants on white blood cell count. Complex Psychiatry, 9(1–4), 1–10.

Sharma, K., Akre, S., Chakole, S., & Wanjari, M. B. (2022). Stress-induced diabetes: A review. Cureus, 14(9), e29142.

Smołucha, G., Steg, A., & Oczkowicz, M. (2024). The role of vitamins in mitigating the effects of various stress factors in pigs breeding. Animals, 14(8), e1218.

Surai, P. F., Kochish, I. I., Fisinin, V. I., & Juniper, D. T. (2019). Revisiting oxidative stress and the use of organic selenium in dairy cow nutrition. Animals, 9(7), e462.

Suresh, P. S., & Koner, B. C. (2012). Effect of acute and chronic stress on leucocyte count: modulation by chlordiazepoxide. Immunopharmacol Immunotoxicol, 34(4), 586–589.

Telles-Correia, D., Barbosa, A., Cortez-Pinto, H., Campos, C., Rocha, N. B., & Machado, S. (2017). Psychotropic drugs and liver disease: A critical review of pharmacokinetics and liver toxicity. World Journal of Gastrointestinal Pharmacology and Therapeutics, 8(1), 26–38.

Willard, M. D., & Tvedten, H. (Eds.). (2012). Small animal clinical diagnosis by laboratory methods. Fifth Edition. Elsevier.

Wysokiński, A., & Szczepocka, E. (2018). Red blood cells parameters in patients with acute schizophrenia, unipolar depression and bipolar disorder. Psychiatria Danubina, 30(3), 323–330.

Zahir, M., Shariatzadeh, S., Khosravi, A., Alshaikh, F. A., Moradi, P., Ghaderi, M., Farsinejad, P., Louyeh, P. A., Ilkhani, S., Nakhaei, P., Taheri, A., Fagheh, A. F., & Akhavan-Sigari, R. (2021). High risk of drug toxicity in social isolation stress due to liver dysfunction: Role of oxidative stress and inflammation. Brain and Behavior, 11(8), e2317.

Zhou, Y., Wang, J., Zhang, D., Liu, J., Wu, Q., Chen, J., Tan, P., Xing, B., Han, Y., Zhang, P., Xiao, X., & Pei, J. (2021). Mechanism of drug-induced liver injury and hepatoprotective effects of natural drugs. Chinese Medicine, 16(1), 135–167.

Zou, Y., Hu, X. M., Zhang, T., Wei, H. K., Zhou, Y. F., Zhou, Z. X., & Peng, J. (2017). Effects of dietary oregano essential oil and vitamin E supplementation on meat quality, stress response and intestinal morphology in pigs following transport stress. Journal of Veterinary Medical Science, 79(2), 328–335.

Published
2026-06-15
How to Cite
Korkh, I., Koreneva, Y., Boiko, V., Gerilovych, I., Korkh, O., Kovalenko, L., Paliy, A., Boiko, N., Kovalenko, L., & Livoshchenko, Y. (2026). Toxicological assessment of a bioactive adaptogenic drug for use in rats and pigs. Regulatory Mechanisms in Biosystems, 17(6), e26103. https://doi.org/10.15421/0226103