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Dietary Iron Overload Differentially Modulates Chemically-Induced Liver Injury in Rats
Hepatic iron overload is well known as an important risk factor for progression of liver diseases; however, it is unknown whether it can alter the susceptibility to drug-induced hepatotoxicity. Here we investigate the pathological roles of iron overload in two single-dose models of chemically-induce...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551424/ https://www.ncbi.nlm.nih.gov/pubmed/32932999 http://dx.doi.org/10.3390/nu12092784 |
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author | Mori, Mutsuki Izawa, Takeshi Inai, Yohei Fujiwara, Sho Aikawa, Ryo Kuwamura, Mitsuru Yamate, Jyoji |
author_facet | Mori, Mutsuki Izawa, Takeshi Inai, Yohei Fujiwara, Sho Aikawa, Ryo Kuwamura, Mitsuru Yamate, Jyoji |
author_sort | Mori, Mutsuki |
collection | PubMed |
description | Hepatic iron overload is well known as an important risk factor for progression of liver diseases; however, it is unknown whether it can alter the susceptibility to drug-induced hepatotoxicity. Here we investigate the pathological roles of iron overload in two single-dose models of chemically-induced liver injury. Rats were fed a high-iron (Fe) or standard diet (Cont) for four weeks and were then administered with allyl alcohol (AA) or carbon tetrachloride (CCl(4)). Twenty-four hours after administration mild mononuclear cell infiltration was seen in the periportal/portal area (Zone 1) in Cont-AA group, whereas extensive hepatocellular necrosis was seen in Fe-AA group. Centrilobular (Zone 3) hepatocellular necrosis was prominent in Cont-CCl(4) group, which was attenuated in Fe-CCl(4) group. Hepatic lipid peroxidation and hepatocellular DNA damage increased in Fe-AA group compared with Cont-AA group. Hepatic caspase-3 cleavage increased in Cont-CCl(4) group, which was suppressed in Fe-CCl(4) group. Our results showed that dietary iron overload exacerbates AA-induced Zone-1 liver injury via enhanced oxidative stress while it attenuates CCl(4)-induced Zone-3 liver injury, partly via the suppression of apoptosis pathway. This study suggested that susceptibility to drugs or chemical compounds can be differentially altered in iron-overloaded livers. |
format | Online Article Text |
id | pubmed-7551424 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75514242020-10-14 Dietary Iron Overload Differentially Modulates Chemically-Induced Liver Injury in Rats Mori, Mutsuki Izawa, Takeshi Inai, Yohei Fujiwara, Sho Aikawa, Ryo Kuwamura, Mitsuru Yamate, Jyoji Nutrients Article Hepatic iron overload is well known as an important risk factor for progression of liver diseases; however, it is unknown whether it can alter the susceptibility to drug-induced hepatotoxicity. Here we investigate the pathological roles of iron overload in two single-dose models of chemically-induced liver injury. Rats were fed a high-iron (Fe) or standard diet (Cont) for four weeks and were then administered with allyl alcohol (AA) or carbon tetrachloride (CCl(4)). Twenty-four hours after administration mild mononuclear cell infiltration was seen in the periportal/portal area (Zone 1) in Cont-AA group, whereas extensive hepatocellular necrosis was seen in Fe-AA group. Centrilobular (Zone 3) hepatocellular necrosis was prominent in Cont-CCl(4) group, which was attenuated in Fe-CCl(4) group. Hepatic lipid peroxidation and hepatocellular DNA damage increased in Fe-AA group compared with Cont-AA group. Hepatic caspase-3 cleavage increased in Cont-CCl(4) group, which was suppressed in Fe-CCl(4) group. Our results showed that dietary iron overload exacerbates AA-induced Zone-1 liver injury via enhanced oxidative stress while it attenuates CCl(4)-induced Zone-3 liver injury, partly via the suppression of apoptosis pathway. This study suggested that susceptibility to drugs or chemical compounds can be differentially altered in iron-overloaded livers. MDPI 2020-09-11 /pmc/articles/PMC7551424/ /pubmed/32932999 http://dx.doi.org/10.3390/nu12092784 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mori, Mutsuki Izawa, Takeshi Inai, Yohei Fujiwara, Sho Aikawa, Ryo Kuwamura, Mitsuru Yamate, Jyoji Dietary Iron Overload Differentially Modulates Chemically-Induced Liver Injury in Rats |
title | Dietary Iron Overload Differentially Modulates Chemically-Induced Liver Injury in Rats |
title_full | Dietary Iron Overload Differentially Modulates Chemically-Induced Liver Injury in Rats |
title_fullStr | Dietary Iron Overload Differentially Modulates Chemically-Induced Liver Injury in Rats |
title_full_unstemmed | Dietary Iron Overload Differentially Modulates Chemically-Induced Liver Injury in Rats |
title_short | Dietary Iron Overload Differentially Modulates Chemically-Induced Liver Injury in Rats |
title_sort | dietary iron overload differentially modulates chemically-induced liver injury in rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551424/ https://www.ncbi.nlm.nih.gov/pubmed/32932999 http://dx.doi.org/10.3390/nu12092784 |
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