Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis
Heme oxygenase (HO) breaks down the pro-oxidant heme into carbon monoxide, iron and the antioxidant biliverdin. The isoform HO-1 plays an effective role to counteract oxidative damage and to control inflammation. Prolonged cellular damage due to chronic inflammation is one of the reasons leading to...
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todo:paper_09599673_v85_n4_p213_Caballero2023-10-03T15:53:20Z Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis Caballero, F. Meiss, R. Gimenez, A. Batlle, A. Vazquez, E. Heme oxygenase Hepatocarcinogenesis Inflammation Oxidative stress p-dimethylaminoazobenzene 4 dimethylaminoazobenzene antioxidant biliverdin carbon dioxide heme oxygenase 1 iron animal cell animal experiment animal tissue article cell damage cell proliferation chemical carcinogenesis chronic inflammation controlled study disease course enzyme localization epithelium cell immunohistochemistry inflammation Kupffer cell liver adenoma liver carcinogenesis liver cell liver cell carcinoma liver injury liver necrosis macrophage male morphological trait mouse strain neoplasm nonhuman oxidation oxidative stress priority journal protein expression rat tumor differentiation Western blotting Adenoma Animals Blotting, Western Carcinoma, Hepatocellular Disease Progression Heme Oxygenase (Decyclizing) Heme Oxygenase-1 Hepatocytes Immunoenzyme Techniques Liver Liver Neoplasms Macrophages Male Membrane Proteins Mice Mice, Inbred Strains Necrosis p-Dimethylaminoazobenzene Precancerous Conditions Heme oxygenase (HO) breaks down the pro-oxidant heme into carbon monoxide, iron and the antioxidant biliverdin. The isoform HO-1 plays an effective role to counteract oxidative damage and to control inflammation. Prolonged cellular damage due to chronic inflammation is one of the reasons leading to the development of tumours. The aim of this work was to investigate HO-1 expression and localization along the different stages of chemically induced hepatocarcinogenesis (HCC) and the occurring morphological changes. To provoke sustained oxidative stress and chronic inflammation, CF1 mice received dietary p-dimethylaminoazobenzene (DAB, 0.5%, w/w) during a whole period of 14 months. HO-1 expression increased along the experimental trial in morphologically normal hepatocytes in DAB-treated animals. HO-1 expression diminished in altered hepatic foci (AHF) and oval cells and early preneoplastic lesions. Otherwise, marked HO-1 overexpression was detected in Kupffer cells and macrophages surrounding necrotic and nodular areas. Adenomas showed decreased HO-1 immunostaining. In hepatocellular carcinomas, an inverse relationship was found between the immunohistochemical expression of HO-1 and the degree of tumour differentiation, being negative in poorly differentiated tumours. In our experimental model, down modulation of HO-1 expression correlated with malignancy progression. Thus, our data point to activation of HO-1 as a potential therapeutic tool. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09599673_v85_n4_p213_Caballero |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Heme oxygenase Hepatocarcinogenesis Inflammation Oxidative stress p-dimethylaminoazobenzene 4 dimethylaminoazobenzene antioxidant biliverdin carbon dioxide heme oxygenase 1 iron animal cell animal experiment animal tissue article cell damage cell proliferation chemical carcinogenesis chronic inflammation controlled study disease course enzyme localization epithelium cell immunohistochemistry inflammation Kupffer cell liver adenoma liver carcinogenesis liver cell liver cell carcinoma liver injury liver necrosis macrophage male morphological trait mouse strain neoplasm nonhuman oxidation oxidative stress priority journal protein expression rat tumor differentiation Western blotting Adenoma Animals Blotting, Western Carcinoma, Hepatocellular Disease Progression Heme Oxygenase (Decyclizing) Heme Oxygenase-1 Hepatocytes Immunoenzyme Techniques Liver Liver Neoplasms Macrophages Male Membrane Proteins Mice Mice, Inbred Strains Necrosis p-Dimethylaminoazobenzene Precancerous Conditions |
| spellingShingle |
Heme oxygenase Hepatocarcinogenesis Inflammation Oxidative stress p-dimethylaminoazobenzene 4 dimethylaminoazobenzene antioxidant biliverdin carbon dioxide heme oxygenase 1 iron animal cell animal experiment animal tissue article cell damage cell proliferation chemical carcinogenesis chronic inflammation controlled study disease course enzyme localization epithelium cell immunohistochemistry inflammation Kupffer cell liver adenoma liver carcinogenesis liver cell liver cell carcinoma liver injury liver necrosis macrophage male morphological trait mouse strain neoplasm nonhuman oxidation oxidative stress priority journal protein expression rat tumor differentiation Western blotting Adenoma Animals Blotting, Western Carcinoma, Hepatocellular Disease Progression Heme Oxygenase (Decyclizing) Heme Oxygenase-1 Hepatocytes Immunoenzyme Techniques Liver Liver Neoplasms Macrophages Male Membrane Proteins Mice Mice, Inbred Strains Necrosis p-Dimethylaminoazobenzene Precancerous Conditions Caballero, F. Meiss, R. Gimenez, A. Batlle, A. Vazquez, E. Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis |
| topic_facet |
Heme oxygenase Hepatocarcinogenesis Inflammation Oxidative stress p-dimethylaminoazobenzene 4 dimethylaminoazobenzene antioxidant biliverdin carbon dioxide heme oxygenase 1 iron animal cell animal experiment animal tissue article cell damage cell proliferation chemical carcinogenesis chronic inflammation controlled study disease course enzyme localization epithelium cell immunohistochemistry inflammation Kupffer cell liver adenoma liver carcinogenesis liver cell liver cell carcinoma liver injury liver necrosis macrophage male morphological trait mouse strain neoplasm nonhuman oxidation oxidative stress priority journal protein expression rat tumor differentiation Western blotting Adenoma Animals Blotting, Western Carcinoma, Hepatocellular Disease Progression Heme Oxygenase (Decyclizing) Heme Oxygenase-1 Hepatocytes Immunoenzyme Techniques Liver Liver Neoplasms Macrophages Male Membrane Proteins Mice Mice, Inbred Strains Necrosis p-Dimethylaminoazobenzene Precancerous Conditions |
| description |
Heme oxygenase (HO) breaks down the pro-oxidant heme into carbon monoxide, iron and the antioxidant biliverdin. The isoform HO-1 plays an effective role to counteract oxidative damage and to control inflammation. Prolonged cellular damage due to chronic inflammation is one of the reasons leading to the development of tumours. The aim of this work was to investigate HO-1 expression and localization along the different stages of chemically induced hepatocarcinogenesis (HCC) and the occurring morphological changes. To provoke sustained oxidative stress and chronic inflammation, CF1 mice received dietary p-dimethylaminoazobenzene (DAB, 0.5%, w/w) during a whole period of 14 months. HO-1 expression increased along the experimental trial in morphologically normal hepatocytes in DAB-treated animals. HO-1 expression diminished in altered hepatic foci (AHF) and oval cells and early preneoplastic lesions. Otherwise, marked HO-1 overexpression was detected in Kupffer cells and macrophages surrounding necrotic and nodular areas. Adenomas showed decreased HO-1 immunostaining. In hepatocellular carcinomas, an inverse relationship was found between the immunohistochemical expression of HO-1 and the degree of tumour differentiation, being negative in poorly differentiated tumours. In our experimental model, down modulation of HO-1 expression correlated with malignancy progression. Thus, our data point to activation of HO-1 as a potential therapeutic tool. |
| format |
JOUR |
| author |
Caballero, F. Meiss, R. Gimenez, A. Batlle, A. Vazquez, E. |
| author_facet |
Caballero, F. Meiss, R. Gimenez, A. Batlle, A. Vazquez, E. |
| author_sort |
Caballero, F. |
| title |
Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis |
| title_short |
Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis |
| title_full |
Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis |
| title_fullStr |
Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis |
| title_full_unstemmed |
Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis |
| title_sort |
immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis |
| url |
http://hdl.handle.net/20.500.12110/paper_09599673_v85_n4_p213_Caballero |
| work_keys_str_mv |
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| _version_ |
1782026899772407808 |