Expression of the apoptosis marker caspase-3 in toxic hepatitis caused by tetrachloromethane in the liver

Introduction. Despite significant attention to the study of the mechanisms of toxic liver damage in recent years, there are still very few effective treatment methods. Liver damage caused by carbon tetrachloride results in hepatocyte death, including apoptosis. The purpose of the study was to study histological changes and immunohistochemical investigation of the expression of the apoptosis marker caspase-3 in a model of toxic liver injury induced by CCl4 with hepatoprotective correction. Materials and methods. The experiment involved forty five rats divided into 9 groups. CCl4 oil solution was used as the toxicant for each rat group except the negative control groups. Hepatoprotective correction was performed using “Heptor”, “Mexidol”, and Oxymethyluracil. Correction was carried out twice (sacrifice after 24 hours) and four times (sacrifice after 72 hours) following a single CCl4 injection. Liver tissues underwent standard histological processing with hematoxylin-eosin staining and immunohistochemical analysis for caspase-3. The number of caspase-3-positive cells was evaluated using a pre-trained YOLOv5 deep learning model. Results. After 24 hours of intoxication, no statistically significant differences in the number of caspase-3-positive cells on microphotographs were found in the experimental groups (p=0.087). However, after 72 hours of CCl4 administration, statistically significant differences were observed between the groups (p=0.020). Multiple comparisons showed statistically significant differences between the negative control and positive control groups (p=0.0076), as well as between the positive control group and the group corrected with Oxymethyluracil (p=0.0254). Limitations. The limitations of the study include the evaluation of histological changes and the expression of the apoptosis marker caspase-3 only at 24 and 72 hours after intoxication without long-term studies, the use of a relatively small number of animals (45 rats), and the reliance solely on standard histological methods, immunohistochemical analysis, and deep learning techniques. Conclusion: After 72 hours, the positive and negative control groups differed from each other, indicating an exacerbation of apoptosis processes after CCl4 administration. The group corrected with Oxymethyluracil demonstrated fewer caspase-3-positive cells compared to the positive control group, suggesting the hepatoprotective effect of this drug.

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Journal
Hygiene and Sanitation
Published
2025-03-07
DOI
https://doi.org/10.47470/0016-9900-2025-104-2-234-238
Primary Topic
Drug-Induced Hepatotoxicity and Protection
Type
article
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article

Expression of the apoptosis marker caspase-3 in toxic hepatitis caused by tetrachloromethane in the liver

Elvira F. Repina, Samat S. Baygildin, Д О Каримов, Eldar R. Kudoyarov et al.
Hygiene and Sanitation
Drug-Induced Hepatotoxicity and Protection
article

Expression of the apoptosis marker caspase-3 in toxic hepatitis caused by tetrachloromethane in the liver

Elvira F. Repina, Samat S. Baygildin, Д О Каримов, Eldar R. Kudoyarov, Nadezhda Yu. Khusnutdinova, A.R. Akhmadeev, Yana V. Valova, Denis A. Smolyankin
article en

Abstract

Introduction. Despite significant attention to the study of the mechanisms of toxic liver damage in recent years, there are still very few effective treatment methods. Liver damage caused by carbon tetrachloride results in hepatocyte death, including apoptosis. The purpose of the study was to study histological changes and immunohistochemical investigation of the expression of the apoptosis marker caspase-3 in a model of toxic liver injury induced by CCl4 with hepatoprotective correction. Materials and methods. The experiment involved forty five rats divided into 9 groups. CCl4 oil solution was used as the toxicant for each rat group except the negative control groups. Hepatoprotective correction was performed using “Heptor”, “Mexidol”, and Oxymethyluracil. Correction was carried out twice (sacrifice after 24 hours) and four times (sacrifice after 72 hours) following a single CCl4 injection. Liver tissues underwent standard histological processing with hematoxylin-eosin staining and immunohistochemical analysis for caspase-3. The number of caspase-3-positive cells was evaluated using a pre-trained YOLOv5 deep learning model. Results. After 24 hours of intoxication, no statistically significant differences in the number of caspase-3-positive cells on microphotographs were found in the experimental groups (p=0.087). However, after 72 hours of CCl4 administration, statistically significant differences were observed between the groups (p=0.020). Multiple comparisons showed statistically significant differences between the negative control and positive control groups (p=0.0076), as well as between the positive control group and the group corrected with Oxymethyluracil (p=0.0254). Limitations. The limitations of the study include the evaluation of histological changes and the expression of the apoptosis marker caspase-3 only at 24 and 72 hours after intoxication without long-term studies, the use of a relatively small number of animals (45 rats), and the reliance solely on standard histological methods, immunohistochemical analysis, and deep learning techniques. Conclusion: After 72 hours, the positive and negative control groups differed from each other, indicating an exacerbation of apoptosis processes after CCl4 administration. The group corrected with Oxymethyluracil demonstrated fewer caspase-3-positive cells compared to the positive control group, suggesting the hepatoprotective effect of this drug.

Hygiene and SanitationVol. 104(2)
Ufa Research Institute of Occupational Health and Human Ecology (RU)
Russian Academy of Sciences
Openalex Percentile: Top 94%
Drug-Induced Hepatotoxicity and Protection
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