Impact of 1,2,4-thio-triazole derivative-based liniment on morphological and immunological blood parameters of dogs suffering from dermatomycoses
AbstractThe development of new preparations in soft medical form with antifungal effect and the ability to exert an antimicrobial effect on the secondary microflora accompanying the infection with accompanying desensitizing action is extremely relevant, as well as introduction of such drugs into veterinary medicine. The compound and compounding of the preparation with fungicidal and fungistatic effects for the treatment of dermatitides of dogs and cats caused by fungal skin infection are substantiated. The active agent of the developed medicine in the form of liniment was the S-derivative of triazole, and the base material was the standardized oil from milk thistle Silybum marianum. We determined the dynamics of the morphological parameters in blood of dogs with typical clinical skin pathology and its laboratory-confirmed fungal etiology. During the treatment of dogs with confirmed laboratory diagnosis “dermatophytosis”, the main medical preparation used was VetMikiDerm. It was heated on a water bath, gently applied and in thin layer was applied to the infected areas of skin 2–3 times a day over the period of treatment. Positive dynamics of recovery were seen already at 3–4th days of the treatment (skin hyperaemia, itching and signs of inflammation reduced). On the 10–14th days of the treatment, the signs of regeneration of skin and recovery of the coat were observed. In all cases without exception (regardless of the area of skin infected by fungus) in this period, no fungi were microscopically found in the scrapes. Use of VetMikoDerm preparation during the course of the treatment, against the background of inhibition of the inflammatory processes, relief from itch and gradual recovery of the epidermis and hair, also contributed to the activation of the functional condition of the liver (the activity of amino transferases decreased, while the concentration of urea increased). Minimization of the negative effect of the products of fungal intoxication, after use of the tested preparation for a medical purpose, led to recovery of the functional state of the cellular link of the immunity. The treatment effect of the newly-developed preparation must be related to the active substance with notable fungicidal effect. Thio-triazole derivative exerts its medical effect by inhibiting sterol biosynthesis and contributes to the decrease in the content of ergosterol necessary for proliferation and growth of cells of fungus. The oil of milk thistle used as base material for liniment provides not only high quality of medical form in the process of production and maintenance, and adds to the effect of the main substance. Due to flavonoids, vitamins, carotenoids, milk thistle improves the condition of the skin, contributes to its active regeneration, stimulates reparation processes and recovery of the epidermis and the coat. Against the background of the effective fungicidal effect, the newly-developed VetMikoDerm preparation in the form of liniment exerted anti-inflammatory, hepatoprotective, immune-stimulating, wound-healing, regenerative and anti-itch effects.
Bila, N. V., Hlebeniuk, V. V., Zubkov, V. V., & Voronov, T. V. (2014). Epizootolohichni osoblyvosti dermatomikoziv u m. Dnipropetrovsk [Epizootologic peculiarities of dermatomycoses in Dnipropetrovsk]. Naukovo-Tekhnichnyi Biuleten NNTs Biobezpeky ta Ekolohichnoho Kontroliu Resursiv APK, 2(3), 63–67 (in Ukrainian).
Bilaj, V. I. (1989). Osnovy obshhej mikologii [Basics of general mycology]. Vysshaja Shkola, Kyiv (in Russian).
Bilous, S. B., Kalyniuk, T. H., & Gudz, N. I. (2010). Aktualni pytannia farmatsevtychnoi rozrobky miakykh likarskykh zasobiv dlia zovnishnoho zastosuvannia [Relevant issues of pharmacological development of soft external medical preparations]. Farmatsevtychnyi Zhurnal, 2, 16–27 (in Ukrainian).
Borysevych, V. B., Medvediev, K. S., & Ihnatenko, A. A. (2000). Khvoroby shkiry u sobak [Skin diseases of dogs]. Visnyk Bilotserkivskoho Derzhavnoho Ahrarnoho Universytetu, 11, 5–8 (in Ukrainian).
Bublyk, O., Lemeshchenko, H., & Tytarenko, V. (2004). Epizootychna sytuatsiia z trykhofitii kotiv i sobak u m. Kyievi [Epizootic situation with trichophitia among cats and dogs in Kyiv]. Veterynarna Medytsyna Ukrainy, 3, 9–11 (in Ukrainian).
Del Rosso, Y. Q., & Cupta, A. K. (2000). An evaluation of intermittent therapies used to treat onychomycosis and other dermatomycoses with the oral antifungal agents. International Journal of Dermatology, 39(6), 401–411.
Fraschini, F., Dermartini, G., & Esposti, D. (2002). Pharmacology of silymarin. Clinical Drug Investigation, 22(1), 51–65.
Hamza, R. Z., & Al-Harbi, M. S. (2015). Silymarin and Nigella sativa extract ameliorate paracetamol induced oxidative stress and renal dysfunction in male mice. Asian Pacific Journal of Tropical Disease, 5(1), 169–174.
Iovenko, A. V., & Koval, G. M. (2019). Monitoring of contagious skin diseases of dogs and cats in Odessa. Scientific Messenger of Lviv National University of Veterinary Medicine and Biotechnologies, Series Veterinary Sciences, 93, 160–163.
Ismaili, S. A., Harhar, H., Gharby, S., & Bourazmi, H. (2016). Chemical composition of two nonconventional oils in Morocco: Melia azadirachta and Silybum marianum (L). Journal of Materials and Environmental Science, 7(6), 2208–2213.
Ivanov, H., & Atamas, V. (2003). Retrospektyvnyi epizootolohichnyi analiz zakhvoriuvanosti ta yii sezonnosti pry dermatomikozakh sobak i kotiv [Retrospective epizootologic analysis of the morbidity and its seasonality at dermatomycoses of dogs and cats]. Veterynarna Medytsyna Ukrainy, 4, 29–31 (in Ukrainian).
Karimi, G., Hassanzadeh-Josan, S., Memar, B., Esmaeili, S. A., & Riahi-Zanjani, B. (2018). Immunomodulatory effects of silymarin after subacute exposure to mice: A tiered approach immunotoxicity screening. Journal of Pharmacopuncture, 21(2), 90–97.
Katiyar, S. K., Mantena, S. K., & Meeran, S. M. (2011). Silymarin protects epidermal keratinocytes from ultraviolet radiation-induced apoptosis and DNA damage by nucleotide excision repair mechanism. PLoS One, 6(6), e21410.
Katunina, O. R. (2009). Sovremennye predstavlenija ob uchastii kozhi v immunnyh processah [Modern knowledge about participation of the skin in immune processes]. Vestnik Dermatologii i Venerologii, 2, 39–46 (in Russian).
Khariv, M., Gutyj, B., Butsyak, V., & Khariv, I. (2016). Hematological indices of rat organisms under conditions of oxidative stress and liposomal preparation action. Biological Bulletin of Bogdan Chmelnitskiy Melitopol State Pedagogical University, 6(1), 276–289.
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.
Kim, N. C., Graf, T. N., Sparacino, C. M., Wani, M. C., & Wall, M. E. (2003). Complete isolation and characterization of silybins and isosilybins from milk thistle (Silybum marianum). Organic and Biomolecular Chemistry, 1(10), 1684–1689.
Kovalenko, A. H., & Voronkova, O. S. (2018). Vyiavlennia infektsiinykh urazhen, vyklykanykh mikroskopichnymyhrybamy, u tvaryn. [Discovery of infectious problems caused by microscopic fungi in animals]. Visnyk Problem Biolohii i Medytsyny, 147, 107–110 (in Ukrainian).
Kren, V., & Walterova, D. (2005). Silybin and silymarin – new effects and applications. Biomed Papers, 149(1), 29–41.
Luk'janovskij, V. A. (1995). Bolezni kozhi i podkozhnoj kletchatki u sobak [Diseases of the skin and subcutaneous cells in dogs]. Veterinarija, 3, 47–55 (in Russian).
Martynyshyn, V. P., Gunchak, V. M., Gutyj, B. V., & Hlukh, O. S. (2017). To the method of preparation of the liniment on the basis of thiopropyl triazole and his assessment of physical properties and performance on individual microorganisms and fungi. Scientific Messenger of Lviv National University of Veterinary Medicine and Biotechnologies, 82, 36–40.
Martynyshyn, V., Hunchak, V., Parchenko, V., Gutyi, B., & Shcherbyna, R. (2018). Evaluation of a new antifungal drug cumulative powers based on 1,2,4-triazole derivatives. Wroclaw. Pp. 113–118.
Martyshuk, T. V., Gutyj, B. V., & Vishchur, O. I. (2016). Level of lipid peroxidation products in the blood of rats under the influence of oxidative stress and under the action of liposomal preparation of ‘‘Butaselmevit’’. Biological Bulletin of Bogdan Chmelnitskiy Melitopol State Pedagogical University, 6(2), 22–27.
Medvedev, K. S. (1999). Bolezni kozhi sobak i koshek [Skin diseases of dogs and cats]. Virma, Kiev (in Russian).
Mercer, D. K., Robertson, J., Wright, K., Miller, L., Smith, S., Stewart, C. S., & O Neil, D. A. (2013). A prodrug approach to the use of coumarins as potential therapeutics for superficial mycoses. PLoS One, 18, e80760.
Olszewska, B., Imko-Walczuk, B., Nowicki, R., Dębska-Ślizień, A., Wilkowska, A., & Rutkowski, B. (2016). Superficial and deep cutaneous fungal infections in solid organ transplant recipients. Dermatology Review/Przegląd Dermatologiczny, 103(4), 259–272.
Paterson, S. (2011). Kozhnye bolezni sobak [Skin diseases of dogs]. Akvarium, Moscow (in Russian).
Rosen, T. (1997). Dermatophytosis: Diagnostic pointers and therapeutic pitfalis. Consultant, 37, 1545–1557.
Ruban, A. M. (2013). Shkirni zakhvoriuvannia u sobak. [Scheme of illness in dogs]. Veterynarna Medytsyna, 212, 36–37 (in Ukrainian).
Sati, J., Mohanty, B. P., Garg, M. L., & Koul, A. (2016). Pro-oxidant role of silibinin in DMBA/TPA induced skin cancer: 1H NMR metabolomic and biochemical study. PloS One, 11(7), e0158955.
Shcherbyna, R., Parchenko, V., Martynyshyn, V., & Hunchak, V. (2018). Evaluation of acute and subacute toxicity of oil liniment based on 4-((5(decylthio)-4methyl-4H-1,2,4-triazol-3YL)methyl)morpholine. Ankara Universitesi Eczacilik Fakultesi Dergisi, 42(1), 43–52.
Vashchenko, O. O., Kalyniuk, T. H., & Zaichenko, O. I. (2009). Porivnialna otsinka suchasnykh protyhrybkovykh likarskykh zasobiv dlia systemnoho likuvannia onikhomikoziv [Comparative evaluation of contemporary antifungal medical preparations for systemic treatment of onichomicosis]. Klinichna Farmatsiia, 13(4), 17–22 (in Ukrainian).
Vlislo, V. V. (2012). Laboratorni metody doslidzhen u biolohii, tvarynnytstvi ta veterynarniy medytsyni [Laboratory methods of research in biology, animal husbandry and veterinary medicine]. Spolom, Lviv (in Ukrainian).
Wu, J.-P., Tsai, C.-C., Yeh, Y.-L., Lin, Y.-M., Lin, C.-C., Day, C. H., Shen, C.-Y., Padma, V. V., Pan, L.-F., & Yang, C. (2015). Silymarin accelerates liver regeneration after partial hepatectomy. Hepatoprotective Potential of Herbal Medicine, 2015, 603529.
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.
Zhao, J., Lahiri-Chatterjee, M., Sharma, Y., & Agarwal, R. (2000). Inhibitory effect of a flavonoid antioxidant silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. Carcinogenesis, 21(4), 811–816.
Zhuk, A. O., Petrenko, O. F., & Petrenko, O. O. (2017). Stan nespetsyfichnoi rezystentnosti v sobak za ran Condition of non-specific resistance in dogs with wounds]. Naukovyi visnyk Veterynarnoi Medytsyny, 2, 84–91 (in Ukrainian).
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons «Attribution» 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.