HEPATOPROTECTIVE EFFECT OF THE HUMAN PLACENTA HYDROLYSATE PREPARATION ON AN EXPERIMENTAL MODEL OF TOXIC LIVER DAMAGE WITH PARACETAMOL


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Abstract

Hepatoprotectors are used for the treatment of medicinal liver lesions. The paper presents the results of a study of human placenta hydrolysates (HPH) in toxic liver damage with paracetamol. Course administration of HRP in animals with a model of acute hepatocyte injury led to a significant decrease in markers of liver dysfunction. The hepatoprotective effect of HPH was confirmed by histological examination.

Full Text

Relevance. According to the global database of registered adverse complications when taking medications (VigiBase, https://who-umc . org/vigibase/) for 2022, hepatotoxicity is the most common side effect [1]. Paracetamol occupies a leading position in the frequency of cases of liver damage (LiverTox® (http://livertox.nlm.nih.gov ). Paracetamol-based drugs belong to the over-the-counter group, which increases the risk of self-medication and exceeding the recommended dose [3]. Hydrolysates of the human placenta are one of the promising areas of hepatoprotection. "Laennek" (registration number: P No. 0138851/01, Japan) is a preparation based on human placenta hydrolysate containing peptide fragments, vitamins, amino acids, macro- and microelements showing hepatoprotective effects, has an immunomodulatory effect.

The aim of the study was to study the hepatoprotective effect of the HRP drug on a model of acute hepatitis caused by paracetamol in rats.

Materials and methods. The study was conducted on 24 white male rats. The animals were divided into 4 groups: group 1 - control-intact; 2 and 4 groups of animals were injected with the drug HRP at a dose of 0.6 ml / kg of weight per day intramuscularly for 14 days; in group 3 and 4 animals, a model of acute hepatitis was reproduced by intragastric administration of paracetamol at a dose of 1000 mg / kg of weight per day day [2]. On the 15th day of the study, the animals were anesthetized, blood was taken for biochemical examination (AST, ALT, total protein, direct and total bilirubin, MDA) and sectional material (liver) for pathohistological examination. Statistical processing by the program "Statistica 6.0".

The results of the study showed that twice taking high doses of paracetamol led to an increase in the level of ALT, total bilirubin and MDA; the use of the drug HRP Laennek for 2 weeks in animals with a model of acute liver damage with paracetamol contributed to a significant decrease in the level of ALT, total bilirubin and MDA. The results of pathohistological analysis: in the control group and the group of animals treated with HRP, the microscopic picture of liver tissue corresponded to the norm; in the third group of animals injected with paracetamol, moderate fullness of central veins and sinusoids was noted, lymph-histiocytic infiltrate with an admixture of single eosinophils was formed in the stroma of portal tracts, hydropic dystrophy acquired a subtotal character, intracellular cholestasis; in the fourth group of animals injected with a combination of paracetamol and HRP - signs of venous fullness of the liver were moderately pronounced, hydropic dystrophy of hepatocytes was focal.
Conclusions.
Double administration of paracetamol at a dose of 1000 mg / kg of weight in rats led to liver damage. The introduction of HRP in animals with a model of acute liver injury contributed to the normalization of ALT, MDA, and bilirubin levels. Histological examination confirmed that the administration of paracetamol led to the development of acute hepatitis. The use of HRP reduced parenchymal damage and increased hepatocyte regeneration.

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About the authors

Igor Aleksandrovich Alekseev

Ivanovo State Medical Academy

Email: alekseevigor19022001@gmail.com
ORCID iD: 0009-0008-0555-5298
Russian Federation, 8, Sheremetevsky prospect, Ivanovo, 153012, Russia

Ivan Andreevich Peresadko

Ivanovo State Medical Academy

Email: Ivan.peresadko@mail.ru
ORCID iD: 0009-0001-4586-5628
Russian Federation, 8, Sheremetevsky prospect, Ivanovo, 153012, Russia

Andrey Andreevich Ilyasov

Ivanovo State Medical Academy

Email: ya.a02@mail.ru
ORCID iD: 0009-0009-0333-8182
Russian Federation, 8, Sheremetevsky prospect, Ivanovo, 153012, Russia

Yaroslav Maksimovich Milchikov

Ivanovo State Medical Academy

Email: milchicov@mail.ru
ORCID iD: 0009-0003-9662-2161
Russian Federation, 8, Sheremetevsky prospect, Ivanovo, 153012, Russia

Arina Mikhailovna Osipova

Ivanovo State Medical Academy

Email: armioisva.ru@mail.ru
ORCID iD: 0009-0002-4597-2703
Russian Federation, 8, Sheremetevsky prospect, Ivanovo, 153012, Russia

Natalya Andreevna Terentyeva

Ivanovo State Medical Academy

Author for correspondence.
Email: n.terentjeva98@gmail.com
ORCID iD: 0009-0007-3948-8102
Russian Federation, 8, Sheremetevsky prospect, Ivanovo, 153012, Russia

References

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  2. Руководство по проведению доклинических исследований лекарственных средств. Под ред. Миронова А.Н. Часть первая. — М.: Гриф и К, 2012. — 944 с.
  3. Харкевич, Д. А. Фармакология : учебник / Д. А. Харкевич. - 13-е изд. , перераб. - Москва : ГЭОТАР-Медиа, 2021. - 752 с.

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