THE MORPHOLOGICAL STRUCTURE OF THE LIVER AND ITS FUNCTIONAL STATE AT MEDICINAL DAMAGE AND TREATMENT BY THE NEW PHARMACEUTICAL COMPOSITION

The study presented results of exploration of liver functional activity and morphological structure on the experimental model of drug-induced hepatitis by twice administration of 1000 mg/kg acetaminophen to nonlinear both sexes white rats treated by preventive administration of novel pharmaceutic formulation with laboratory code LHT-8-16. The substance was administered to the animals intra-gastrically 1 hour prior to acetaminophen intake. We studied changes in biochemical blood indices, which characterize the functional activity of the liver, assessed the organ histological structure, and performed macro- and micro-morphometric analysis. It has been shown that the substance LHT-8-16 prevents the toxic effect of acetaminophen on the functional activity of the liver, which was displayed in the decrease of activity of drug-induced cytolytic and cholestatic syndromes, normalizing the level of total bilirubin in rats’ serum. The appearance of the liver, its relative and absolute weight in animals with drug-induced hepatitis, who received LHT-8-16, was comparable with the intact rats. On histological specimens stained with hematoxylin and eosin we observed a decrease in the area of necrosis of hepatic parenchyma, preservation of tissue structure. Hyperemia and extending sinusoids occurred on the periphery of the body and were less pronounced in comparison with the control group. The area of the cytoplasm, the nuclei and the nuclear-cytoplasmic ratio approximated the values of the intact group. The appearance of multi-nuclear hepatocytes referred to the activation of the synthetic activity of the liver and onset of regeneration mechanisms. Thus, it can be concluded that the studied formulation possesses hepatoprotective property.

liver morphology, drug-induced hepatitis, paracetamol, drug LKHT-8-16

1. Bataller L, Hadengue A, Zoulim F. Barselona. Spain. 2012;1:35-40.

2. Lopatkina TN, Burnevich EZ. Lekarstvennye porageniy pecheni. Prakticheskaya gepatologiya. 2004;133-136.

3. Polunina TE. iDoctor.2013:5:23-28.

4. Bjornsson E, Olsson R. Outcome and prognostic markers insevere drug induced liver disease. Hepatology. 2005;42:481-489.

5. Koroleva MV. Exogennj-toxicheskii gepatit. Sovremennyi vzglyad na etiologiu, patogenez, klinicheskoe techenie. Lekarstvennyi vestnik. 2015;2(58)9:18-22.

6. Kafrouni MI, Anders RA, Verma S. Gepatotoxichnost, obuslovlennaya primeneniem dieticheskih dobavok, sodergashih anaboliticheskie steroidy. Clinicheskaya Gastroenterologya i gepatologiya. 2009;2(3):163-167.

7. Eremina EU. Lekarstvennyi gepatit. Practicheskaya medicina. 2014;1(77):20-29.

8. Kullak-Ublick GA, Andrade RJ, Merz M et al. Drug-induced liver injury: recent advances in diagnosis and risk assessment Gut. 2017;3:1-11.

9. Rivera P, Pastor A, Arrabal S et al. Acetaminophen-induced liver injury alters the acyl ethanolamine-based anti-inflammatory signaling system in liver. Front Pharmacol. 2017;8:705.

10. Ratziu V, Harrison SA, Francque S et al. Elafibranor, an agonist of the peroxisome proliferator-activated receptor-α and -δ, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening. Gastroenterology. 2016;150:1147-1159.