P- 78 DIETHYlNITROSAMINE AND 2-ACETYLAMINOFLUORENE CHRONIC ADMINISTRATION LEADS TO BIOCHEMICAL, HISTOLOGIC AND GENETIC CHANGES RELATED TO HEPATOCELLULAR CARCINOMA IN WISTAR RATS
Introduction and Objectives: Hepatocellular carcinoma (HCC) is one of the neoplasms with the highest mortality worldwide. The causes of the development of HCC have been related to hepatitis B virus and exposure to aflatoxin B1; however, chronic alcohol use, nonalcoholic fatty liver disease, and hepa...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Annals of Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268123000777 |
| _version_ | 1797862217707683840 |
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| author | Jaime Sánchez-Meza Marina Campos-Valdez José Alfredo Domínguez-Rosales Saraí Citlalic Rodríguez-Reyes Erika Martínez-López Juliana Marisol Godínez-Rubí Adriana María Salazar-Montes Laura Verónica Sánchez-Orozco |
| author_facet | Jaime Sánchez-Meza Marina Campos-Valdez José Alfredo Domínguez-Rosales Saraí Citlalic Rodríguez-Reyes Erika Martínez-López Juliana Marisol Godínez-Rubí Adriana María Salazar-Montes Laura Verónica Sánchez-Orozco |
| author_sort | Jaime Sánchez-Meza |
| collection | DOAJ |
| description | Introduction and Objectives: Hepatocellular carcinoma (HCC) is one of the neoplasms with the highest mortality worldwide. The causes of the development of HCC have been related to hepatitis B virus and exposure to aflatoxin B1; however, chronic alcohol use, nonalcoholic fatty liver disease, and hepatitis C virus infection are the most important risk factors for developing HCC. The establishment of animal models of HCC is crucial for both basic and translational studies of hepatocellular carcinoma and is a valuable tool to identify alterations during the progression of the disease. This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a model of chemical hepatocarcinogenesis by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Materials and Methods: Twelve Wistar rats weighing 180 to 200 g were divided into control and damage groups: rats were treated with DEN (50 mg/kg/wk) i.p and an intragastric dose of 2-AAF (25 mg/kg/wk) for 18 weeks. Serum clinical biochemistry was performed on VITROS Chemistry System 350® equipment. Masson's trichrome and Hematoxylin-Eosin stains were performed on the liver tissue. Relative gene expression was performed by RT-qPCR in LightCycler®96. Results: The damage group had significant increases in total cholesterol, HDL-C, AST, ALT, ALKP, and GGT. Furthermore, histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa distributed between portal triads and collagen fibers through the hepatic sinusoids. The expression of TGFb1 was significantly increased (p<0.05); on the contrary, ALB, CAT and, PPARα were downregulated (P<0.05), CPT1A was downregulated too but without significance. Conclusions: Chronic administration of DEN and 2-AAF induces characteristic alterations of hepatocellular carcinoma in Wistar rats. The uncontrolled proliferation of malignant cells requires a constant supply of energy and macromolecules. In this work, cancer cells reprogrammed their fatty acid oxidation pathway by downregulation of PPARα and CPT1A. |
| first_indexed | 2024-04-09T22:16:45Z |
| format | Article |
| id | doaj.art-f2b9701d190a491198c83f3b5a61f53b |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-04-09T22:16:45Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-f2b9701d190a491198c83f3b5a61f53b2023-03-23T04:34:15ZengElsevierAnnals of Hepatology1665-26812023-03-0128100973P- 78 DIETHYlNITROSAMINE AND 2-ACETYLAMINOFLUORENE CHRONIC ADMINISTRATION LEADS TO BIOCHEMICAL, HISTOLOGIC AND GENETIC CHANGES RELATED TO HEPATOCELLULAR CARCINOMA IN WISTAR RATSJaime Sánchez-Meza0Marina Campos-Valdez1José Alfredo Domínguez-Rosales2Saraí Citlalic Rodríguez-Reyes3Erika Martínez-López4Juliana Marisol Godínez-Rubí5Adriana María Salazar-Montes6Laura Verónica Sánchez-Orozco7Institute of Chronic Degenerative Diseases, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara Jalisco, MexicoInstitute of Chronic Degenerative Diseases, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara Jalisco, MexicoInstitute of Chronic Degenerative Diseases, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara Jalisco, MexicoInstitute of Nutrigenetics and Translational Nutrigenomics, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara Jalisco, MexicoInstitute of Nutrigenetics and Translational Nutrigenomics, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara Jalisco, MexicoDiagnostic Pathology and Immunohistochemistry Laboratory, Department of Microbiology and Pathology, University Center of Health Sciences, University of Guadalajara, Guadalajara Jalisco, MexicoInstitute of Chronic Degenerative Diseases, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara Jalisco, MexicoInstitute of Chronic Degenerative Diseases, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara Jalisco, MexicoIntroduction and Objectives: Hepatocellular carcinoma (HCC) is one of the neoplasms with the highest mortality worldwide. The causes of the development of HCC have been related to hepatitis B virus and exposure to aflatoxin B1; however, chronic alcohol use, nonalcoholic fatty liver disease, and hepatitis C virus infection are the most important risk factors for developing HCC. The establishment of animal models of HCC is crucial for both basic and translational studies of hepatocellular carcinoma and is a valuable tool to identify alterations during the progression of the disease. This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a model of chemical hepatocarcinogenesis by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Materials and Methods: Twelve Wistar rats weighing 180 to 200 g were divided into control and damage groups: rats were treated with DEN (50 mg/kg/wk) i.p and an intragastric dose of 2-AAF (25 mg/kg/wk) for 18 weeks. Serum clinical biochemistry was performed on VITROS Chemistry System 350® equipment. Masson's trichrome and Hematoxylin-Eosin stains were performed on the liver tissue. Relative gene expression was performed by RT-qPCR in LightCycler®96. Results: The damage group had significant increases in total cholesterol, HDL-C, AST, ALT, ALKP, and GGT. Furthermore, histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa distributed between portal triads and collagen fibers through the hepatic sinusoids. The expression of TGFb1 was significantly increased (p<0.05); on the contrary, ALB, CAT and, PPARα were downregulated (P<0.05), CPT1A was downregulated too but without significance. Conclusions: Chronic administration of DEN and 2-AAF induces characteristic alterations of hepatocellular carcinoma in Wistar rats. The uncontrolled proliferation of malignant cells requires a constant supply of energy and macromolecules. In this work, cancer cells reprogrammed their fatty acid oxidation pathway by downregulation of PPARα and CPT1A.http://www.sciencedirect.com/science/article/pii/S1665268123000777 |
| spellingShingle | Jaime Sánchez-Meza Marina Campos-Valdez José Alfredo Domínguez-Rosales Saraí Citlalic Rodríguez-Reyes Erika Martínez-López Juliana Marisol Godínez-Rubí Adriana María Salazar-Montes Laura Verónica Sánchez-Orozco P- 78 DIETHYlNITROSAMINE AND 2-ACETYLAMINOFLUORENE CHRONIC ADMINISTRATION LEADS TO BIOCHEMICAL, HISTOLOGIC AND GENETIC CHANGES RELATED TO HEPATOCELLULAR CARCINOMA IN WISTAR RATS Annals of Hepatology |
| title | P- 78 DIETHYlNITROSAMINE AND 2-ACETYLAMINOFLUORENE CHRONIC ADMINISTRATION LEADS TO BIOCHEMICAL, HISTOLOGIC AND GENETIC CHANGES RELATED TO HEPATOCELLULAR CARCINOMA IN WISTAR RATS |
| title_full | P- 78 DIETHYlNITROSAMINE AND 2-ACETYLAMINOFLUORENE CHRONIC ADMINISTRATION LEADS TO BIOCHEMICAL, HISTOLOGIC AND GENETIC CHANGES RELATED TO HEPATOCELLULAR CARCINOMA IN WISTAR RATS |
| title_fullStr | P- 78 DIETHYlNITROSAMINE AND 2-ACETYLAMINOFLUORENE CHRONIC ADMINISTRATION LEADS TO BIOCHEMICAL, HISTOLOGIC AND GENETIC CHANGES RELATED TO HEPATOCELLULAR CARCINOMA IN WISTAR RATS |
| title_full_unstemmed | P- 78 DIETHYlNITROSAMINE AND 2-ACETYLAMINOFLUORENE CHRONIC ADMINISTRATION LEADS TO BIOCHEMICAL, HISTOLOGIC AND GENETIC CHANGES RELATED TO HEPATOCELLULAR CARCINOMA IN WISTAR RATS |
| title_short | P- 78 DIETHYlNITROSAMINE AND 2-ACETYLAMINOFLUORENE CHRONIC ADMINISTRATION LEADS TO BIOCHEMICAL, HISTOLOGIC AND GENETIC CHANGES RELATED TO HEPATOCELLULAR CARCINOMA IN WISTAR RATS |
| title_sort | p 78 diethylnitrosamine and 2 acetylaminofluorene chronic administration leads to biochemical histologic and genetic changes related to hepatocellular carcinoma in wistar rats |
| url | http://www.sciencedirect.com/science/article/pii/S1665268123000777 |
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