Acetaldehyde-derived advanced glycation end-products promote alcoholic liver disease.
Chronic ingestion of ethanol increases acetaldehyde and leads to the production of acetaldehyde-derived advanced glycation end-products (AA-AGE). We evaluated the toxicity of AA-AGE on hepatocytes and studied the role of AA-AGE in the pathogenesis of alcoholic liver disease (ALD).Rat hepatocyte cult...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3724722?pdf=render |
| _version_ | 1828232995551576064 |
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| author | Nobuhiko Hayashi Joseph George Masayoshi Takeuchi Atsushi Fukumura Nobuyuki Toshikuni Tomiyasu Arisawa Mikihiro Tsutsumi |
| author_facet | Nobuhiko Hayashi Joseph George Masayoshi Takeuchi Atsushi Fukumura Nobuyuki Toshikuni Tomiyasu Arisawa Mikihiro Tsutsumi |
| author_sort | Nobuhiko Hayashi |
| collection | DOAJ |
| description | Chronic ingestion of ethanol increases acetaldehyde and leads to the production of acetaldehyde-derived advanced glycation end-products (AA-AGE). We evaluated the toxicity of AA-AGE on hepatocytes and studied the role of AA-AGE in the pathogenesis of alcoholic liver disease (ALD).Rat hepatocyte cultures were treated with N-ethyllysine (NEL) or AA-AGE and the cell viability was evaluated using MTT assay. Male Wistar rats were fed with liquid diet containing 5% ethanol for 8 weeks following normal diet for another 12 weeks. A group of animals was sacrificed at 4th, 6th, and 8th week and the remaining animals at 12th, 14th, 16th, 18th, and 20th week. The liver sections were stained for AA-AGE and 4-hydroxy-2-nonenal (4-HNE). Liver biopsy obtained from ALD patients was also stained for AA-AGE and 4-HNE.Hepatocyte viability was significantly reduced in cultures treated with AA-AGE compared to NEL treated or control cultures. Severe fatty degeneration was observed during chronic administration of ethanol increasing from 4-8 weeks. The staining of AA-AGE and 4-HNE was correlated with the degree of ALD in both rat and human. In rats, hepatic fatty degeneration was completely disappeared and the staining for both AA-AGE and 4-HNE returned to normal at 12th week of abstinence. Staining for AA-AGE and 4-HNE was completely absent in normal human liver.The data demonstrated that AA-AGE is toxic to hepatocytes, but not NEL. Chronic ethanol ingestion produces AA-AGE and reactive oxygen species that contribute to the pathogenesis of ALD. Abstinence of alcohol results in complete disappearance of both AA-AGE and 4-HNE along with fatty degeneration suggesting that AA-AGE plays a significant role in the pathogenesis of ALD. |
| first_indexed | 2024-04-12T19:30:56Z |
| format | Article |
| id | doaj.art-ba6218d6dfa84ee9a2a84096e78961aa |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T19:30:56Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ba6218d6dfa84ee9a2a84096e78961aa2022-12-22T03:19:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e7003410.1371/journal.pone.0070034Acetaldehyde-derived advanced glycation end-products promote alcoholic liver disease.Nobuhiko HayashiJoseph GeorgeMasayoshi TakeuchiAtsushi FukumuraNobuyuki ToshikuniTomiyasu ArisawaMikihiro TsutsumiChronic ingestion of ethanol increases acetaldehyde and leads to the production of acetaldehyde-derived advanced glycation end-products (AA-AGE). We evaluated the toxicity of AA-AGE on hepatocytes and studied the role of AA-AGE in the pathogenesis of alcoholic liver disease (ALD).Rat hepatocyte cultures were treated with N-ethyllysine (NEL) or AA-AGE and the cell viability was evaluated using MTT assay. Male Wistar rats were fed with liquid diet containing 5% ethanol for 8 weeks following normal diet for another 12 weeks. A group of animals was sacrificed at 4th, 6th, and 8th week and the remaining animals at 12th, 14th, 16th, 18th, and 20th week. The liver sections were stained for AA-AGE and 4-hydroxy-2-nonenal (4-HNE). Liver biopsy obtained from ALD patients was also stained for AA-AGE and 4-HNE.Hepatocyte viability was significantly reduced in cultures treated with AA-AGE compared to NEL treated or control cultures. Severe fatty degeneration was observed during chronic administration of ethanol increasing from 4-8 weeks. The staining of AA-AGE and 4-HNE was correlated with the degree of ALD in both rat and human. In rats, hepatic fatty degeneration was completely disappeared and the staining for both AA-AGE and 4-HNE returned to normal at 12th week of abstinence. Staining for AA-AGE and 4-HNE was completely absent in normal human liver.The data demonstrated that AA-AGE is toxic to hepatocytes, but not NEL. Chronic ethanol ingestion produces AA-AGE and reactive oxygen species that contribute to the pathogenesis of ALD. Abstinence of alcohol results in complete disappearance of both AA-AGE and 4-HNE along with fatty degeneration suggesting that AA-AGE plays a significant role in the pathogenesis of ALD.http://europepmc.org/articles/PMC3724722?pdf=render |
| spellingShingle | Nobuhiko Hayashi Joseph George Masayoshi Takeuchi Atsushi Fukumura Nobuyuki Toshikuni Tomiyasu Arisawa Mikihiro Tsutsumi Acetaldehyde-derived advanced glycation end-products promote alcoholic liver disease. PLoS ONE |
| title | Acetaldehyde-derived advanced glycation end-products promote alcoholic liver disease. |
| title_full | Acetaldehyde-derived advanced glycation end-products promote alcoholic liver disease. |
| title_fullStr | Acetaldehyde-derived advanced glycation end-products promote alcoholic liver disease. |
| title_full_unstemmed | Acetaldehyde-derived advanced glycation end-products promote alcoholic liver disease. |
| title_short | Acetaldehyde-derived advanced glycation end-products promote alcoholic liver disease. |
| title_sort | acetaldehyde derived advanced glycation end products promote alcoholic liver disease |
| url | http://europepmc.org/articles/PMC3724722?pdf=render |
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