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Comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury
Oxidative stress plays a major part in the pathogenesis of drug-induced liver injury. Yet, overcoming it with other xenobiotics impose additional risks. In this study, we consider the use of natural-occurring and purified Vitamin E analogs as hepatoprotective agents. Vitamin E is well-known for its...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803800/ https://www.ncbi.nlm.nih.gov/pubmed/25637740 http://dx.doi.org/10.1016/j.redox.2015.01.013 |
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author | Tan, Cheau Yih Saw, Tzuen Yih Fong, Chee Wai Ho, Han Kiat |
author_facet | Tan, Cheau Yih Saw, Tzuen Yih Fong, Chee Wai Ho, Han Kiat |
author_sort | Tan, Cheau Yih |
collection | PubMed |
description | Oxidative stress plays a major part in the pathogenesis of drug-induced liver injury. Yet, overcoming it with other xenobiotics impose additional risks. In this study, we consider the use of natural-occurring and purified Vitamin E analogs as hepatoprotective agents. Vitamin E is well-known for its intrinsic antioxidant property even though the differential effect of specific analogs of tocopherol (TP) and tocotrienol (T3) is still not ascertained. This study investigates the protective effect of T3 analogs (α-, δ-, γ−) in comparison with α-TP followed by assessing the underlying mechanisms of the cytoprotective T3 analog(s) in two xenobiotics-induced liver injury models using (1) acetaminophen (APAP)- and (2) hydrogen peroxide (H(2)O(2)). Both α-TP and α-T3 exerted cytoprotective effects while only lower concentration of γ-T3 was effective in inhibiting both toxicants induced injury. α-TP/α-T3 protected hepatocytes from APAP and H(2)O(2)-induced liver injury through arresting free radicals and inhibiting oxidative stress (inhibition of reactive oxygen species, lipid peroxidation and mitochondrial permeability transition). There was also demonstrable inhibition of the apoptotic pathway (inhibition of caspse-3 activity and overexpression of Bcl-(XL)), accompanied with an induction of liver regeneration (PCNA and NF-kB). The cellular uptake of α-T3 was higher than α-TP at the same treatment dosage after 24 h. Overall, α-T3 seems to be a more potent hepatoprotective analog among the tocotrienols and α-TP at the same in vitro treatment dosage. In summary, these results suggest that α-TP/α-T3 elicit hepatoprotective effects against toxicants-induced damage mainly through activation of antioxidant responses at an early stage to prevent the exacerbation of injury. |
format | Online Article Text |
id | pubmed-4803800 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-48038002016-04-06 Comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury Tan, Cheau Yih Saw, Tzuen Yih Fong, Chee Wai Ho, Han Kiat Redox Biol Research Paper Oxidative stress plays a major part in the pathogenesis of drug-induced liver injury. Yet, overcoming it with other xenobiotics impose additional risks. In this study, we consider the use of natural-occurring and purified Vitamin E analogs as hepatoprotective agents. Vitamin E is well-known for its intrinsic antioxidant property even though the differential effect of specific analogs of tocopherol (TP) and tocotrienol (T3) is still not ascertained. This study investigates the protective effect of T3 analogs (α-, δ-, γ−) in comparison with α-TP followed by assessing the underlying mechanisms of the cytoprotective T3 analog(s) in two xenobiotics-induced liver injury models using (1) acetaminophen (APAP)- and (2) hydrogen peroxide (H(2)O(2)). Both α-TP and α-T3 exerted cytoprotective effects while only lower concentration of γ-T3 was effective in inhibiting both toxicants induced injury. α-TP/α-T3 protected hepatocytes from APAP and H(2)O(2)-induced liver injury through arresting free radicals and inhibiting oxidative stress (inhibition of reactive oxygen species, lipid peroxidation and mitochondrial permeability transition). There was also demonstrable inhibition of the apoptotic pathway (inhibition of caspse-3 activity and overexpression of Bcl-(XL)), accompanied with an induction of liver regeneration (PCNA and NF-kB). The cellular uptake of α-T3 was higher than α-TP at the same treatment dosage after 24 h. Overall, α-T3 seems to be a more potent hepatoprotective analog among the tocotrienols and α-TP at the same in vitro treatment dosage. In summary, these results suggest that α-TP/α-T3 elicit hepatoprotective effects against toxicants-induced damage mainly through activation of antioxidant responses at an early stage to prevent the exacerbation of injury. Elsevier 2015-01-20 /pmc/articles/PMC4803800/ /pubmed/25637740 http://dx.doi.org/10.1016/j.redox.2015.01.013 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Tan, Cheau Yih Saw, Tzuen Yih Fong, Chee Wai Ho, Han Kiat Comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury |
title | Comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury |
title_full | Comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury |
title_fullStr | Comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury |
title_full_unstemmed | Comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury |
title_short | Comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury |
title_sort | comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803800/ https://www.ncbi.nlm.nih.gov/pubmed/25637740 http://dx.doi.org/10.1016/j.redox.2015.01.013 |
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