HEPATOTROPIC EFFECTS OF TRIPLE ANTIULCER THERAPY AND PLACENTA CRYOEXTRACT: THE ROLE OF SEX FACTORS IN LIPOPEROXIDATION
I.V. Koshurba1, F.V. Hladkykh2,3, M.O. Chyzh2, I.V. Belochkina2, T.V. Rubleva3
- ’Chernivtsi Regional Perinatal Center’, Chernivtsi, Ukraine
- Institute for Problems of Cryobiology and Cryomedicine of
the National Academy of Sciences of Ukraine, Kharkiv, Ukraine
- State Organization «Grigoriev Institute for Medical
Radiology and Oncology of the National Academy of
Medical Sciences of Ukraine», Kharkiv, Ukraine
The purpose of the work was to reveal the role of sex factors
in the processes of lipid peroxidation (LPO) against the
background of chronic ethanol-tetrachloromethane-induced
liver damage and the hepatotropic effects of triple antiulcer
therapy and cryopreserved placenta extract (CEP). Chronic
ethanol-tetrachloromethane-induced liver damage was induced
by the introduction of a CCl4 solution in combination with
an ethanol solution for 45 days. The content of reactants
with thiobarbituric acid (TBA-active products) and catalase
activity were measured in liver homogenates. Modulation
of the content of sex hormones was achieved by surgical
ovariectomy or testectomy. The study showed that the
combined intravenous administration of esomeprazole,
clarithromycin and metronidazole to rats with chronic
ethanol-tetrachloromethane-induced liver damage caused an
inhibition of the antioxidant defense system, this was indicated
by a statistically significant decrease in catalase activity by
38.4% and a decrease in the antioxidant-prooxidant index by
35.1%, compared with the parameters of intact rats. The most
significant activation of LPO processes was noted in females
against the background of chronic ethanol-tetrachloromethaneinduced liver damage and the administration of anti-ulcer
drugs after ovariectomy. In this case, the content of TBAactive products was 36.1 ± 2.79 μmol/kg of tissue. It was
established that in castrated females, the combined use of
anti-ulcer drugs and CEP against the background of chronic
ethanol-tetrachloromethane-induced liver damage leveled
the activation of LPO processes, this was indicated by a
statistically significant (P < 0.001) 2.7 times lower content of
TBA-active products in liver homogenates.
placenta cryoextract; ethanol-tetrachloromethane liver damage; anti-ulcer drugs; sex hormone content.
- Garcia-Cortes M, Robles-Diaz M, Stephens C, OrtegaAlonso A, Lucena MI, Andrade RJ. Drug induced liver injury: an update. Arch Toxicol. 2020;94(10):3381-407.
- Hamilton LA, Collins-Yoder A, Collins RE. Drug-induced liver injury. Adv Critic Care. 2016;27(4):430-40.
- Burnevich EZ, Krasnova MS. Hepatic encephalopathy in cirrhosis of the liver. Hepatol Forum. 2008;2:19-24.
- Licata A. Adverse drug reactions and organ damage: The liver. Eur J Int Med. 2016;28:9-16.
- Bereda G. Peptic Ulcer disease: definition, pathophysiology, and treatment. J Biomed Biol Sci. 2022;1(2):1-10.
- Hladkykh FV. Experimental study of the antiulcer effect of cryopreserved placenta extract on a model of acetylsalicylic acid-induced ulcerogenesis. Current Issu Pharm Med Sci. 2022;35(2):1-6.
- Koshurba IV, Hladkykh FV, Chyzh MО. Evaluation of antiulcerogenic effect of cryoconservated placenta extract on the model of ethanol-predisonolic lesions of the gastric mucosa. Med Sci Ukr. 2022;18(2):3-9. [Ukrainian].
- Hladkykh FV, Chyzh MO, Manchenko AO, Belochkіna IV, Mikhailova IP. Effect of cryopreserved placenta extract on some biochemical indices of therapeutic efficiency and toxicity of diclofenac sodium in adjuvant-induced experimental arthritis. Pharm Pharmacol. 2021;9(4):278-93.
- Pogozhykh O, Prokopyuk V, Figueiredo C, Pogozhykh D. Placenta and placental derivatives in regenerative therapies: experimental studies, history, and prospects. Stem Cells Int. 2018;2018:1-14.
- Prokopyuk VYu, Prokopyuk OS, Musatova IB, Sorokina IV, Loginova OO, Somova KV. Correction of involutive changes in the reproductive system of late ontogenesis female rat by implantation of cryopreserved fragments of the placenta. Fiziol Zh. 2018; 64(4):74-81.
- Hladkykh FV. The effect of meloxicam and cryopreserved placenta extract on initial inflammatory response - an experimental study. Ceska Slovenska Farm. 2021;70 (5): 179-85.
- Mykytenko AO, Akimov OY, Neporada KS. Influence of lipopolysaccharide on the development of oxidativenitrosative stress in the liver of rats under conditions of chronic alcohol intoxication. Fiziol Zh. 2022;68(2):29-35.
- Rykalo NA. Experimental model of chronic tetrachloromethane hepatitis and liver cirrhosis in immature rats. Матеріал надійшов до редакції 28.07.2022 Actual problems of modern medicine. Bull Ukr Med Stomatol Acad. 2009;9(2):116-8. [Ukrainian].
- Stefanov OV. Preclinical studies of drugs: guidelines. Kyiv: Avicenna; 2001. [Ukrainian].
- Podhirny VV. Hepatotoxic manifestations of lansoprazole, metronidazole and clarithromycin in the experiment. Med Chem. 2007;9(2):74-7. [Ukrainian].
- Hladkykh FV. Gastrocytoprotective properties of cryopreserved placenta extract in combined action of low temperatures and inhibition of cyclooxygenase. Acta Facult Med Naissensis. 2022;39(1):48-56.
- Vogel HG (ed.). Drug discovery and evaluation: Pharmacol Assays Berlin, Heidelberg: Springer Berlin Heidelberg. 2008.
- Aguilar Diaz De Leon J, Borges CR. Evaluation of oxidative stress in biological samples using the thiobarbituric acid reactive substances assay. J Vis Exp. 2020;(159):1-10.
- Vlasits J, Jakopitsch C, Bernroitner M, Zamocky M, Furtmüller PG, Obinger C. Mechanisms of catalase activity of heme peroxidases. Arch Biochem Biophys. 2010;500(1):74-81.
- Zunic L, Skrbo A, Causevic A, Prnjavorac B, Sabanovic Z, Pandza H, Masic I. Role of laboratory diagnostic medical biochemistry services - analysis of requirements for the laboratory test in the laboratory of primary health care center. Med Arсh. 2011;65(4):202-6.
- Aloisi AM. Ceccarelli I, Fiorenzani P. Gonadectomy affects hormonal and behavioral responses to repetitive nociceptive stimulation in male rats. Ann New York Acad Sci. 2003;1007:232-7.
- Joshi SA, Shaikh S, Ranpura S, Khole VV. Postnatal development and testosterone dependence of a rat epididymal protein identified by neonatal tolerization. Reproduction. 2003;125(4):3495-507.
- Zar J.H. Biostatistical analysis (5 ed.). Prentice-Hall, Englewood. 2014.