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New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants
Drug-induced lipid accumulation in the liver may induce two clinically relevant conditions, drug-induced steatosis (DIS) and drug-induced steatohepatitis (DISH). The list of drugs that may cause DIS or DISH is long and heterogeneous and includes therapeutically relevant molecules that cannot be easi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Healthcare
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107075/ https://www.ncbi.nlm.nih.gov/pubmed/33761100 http://dx.doi.org/10.1007/s12325-021-01669-y |
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author | Cataldi, Mauro Citro, Vincenzo Resnati, Chiara Manco, Federica Tarantino, Giovanni |
author_facet | Cataldi, Mauro Citro, Vincenzo Resnati, Chiara Manco, Federica Tarantino, Giovanni |
author_sort | Cataldi, Mauro |
collection | PubMed |
description | Drug-induced lipid accumulation in the liver may induce two clinically relevant conditions, drug-induced steatosis (DIS) and drug-induced steatohepatitis (DISH). The list of drugs that may cause DIS or DISH is long and heterogeneous and includes therapeutically relevant molecules that cannot be easily replaced by less hepatotoxic medicines, therefore making specific strategies necessary for DIS/DISH prevention or treatment. For years, the only available tools to achieve these goals have been antioxidant drugs and free radical scavengers, which counteract drug-induced mitochondrial dysfunction but, unfortunately, have only limited efficacy. In the present review we illustrate how in vitro preclinical research unraveled new key players in the pathogenesis of specific forms of DISH, and how, in a few cases, proof of concept of the beneficial effects of their pharmacological modulation has been obtained in vivo in animal models of this condition. The key issue emerging from these studies is that, in selected cases, liver toxicity depends on mechanisms unrelated to those responsible for the desired, primary pharmacological effects of the toxic drug and, therefore, specific strategies can be designed to overcome steatogenicity without making the drug ineffective. In particular, the hepatotoxic drug could be given in combination with a second molecule intended to selectively antagonize its liver toxicity whilst, ideally, potentiating its desired pharmacological activity. Although most of the evidence that we discuss is from in vitro or animal models and will need to be further explored and validated in humans, it highlights new avenues to be pursued in order to improve the safety of steatogenic drugs. |
format | Online Article Text |
id | pubmed-8107075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-81070752021-05-24 New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants Cataldi, Mauro Citro, Vincenzo Resnati, Chiara Manco, Federica Tarantino, Giovanni Adv Ther Review Drug-induced lipid accumulation in the liver may induce two clinically relevant conditions, drug-induced steatosis (DIS) and drug-induced steatohepatitis (DISH). The list of drugs that may cause DIS or DISH is long and heterogeneous and includes therapeutically relevant molecules that cannot be easily replaced by less hepatotoxic medicines, therefore making specific strategies necessary for DIS/DISH prevention or treatment. For years, the only available tools to achieve these goals have been antioxidant drugs and free radical scavengers, which counteract drug-induced mitochondrial dysfunction but, unfortunately, have only limited efficacy. In the present review we illustrate how in vitro preclinical research unraveled new key players in the pathogenesis of specific forms of DISH, and how, in a few cases, proof of concept of the beneficial effects of their pharmacological modulation has been obtained in vivo in animal models of this condition. The key issue emerging from these studies is that, in selected cases, liver toxicity depends on mechanisms unrelated to those responsible for the desired, primary pharmacological effects of the toxic drug and, therefore, specific strategies can be designed to overcome steatogenicity without making the drug ineffective. In particular, the hepatotoxic drug could be given in combination with a second molecule intended to selectively antagonize its liver toxicity whilst, ideally, potentiating its desired pharmacological activity. Although most of the evidence that we discuss is from in vitro or animal models and will need to be further explored and validated in humans, it highlights new avenues to be pursued in order to improve the safety of steatogenic drugs. Springer Healthcare 2021-03-24 2021 /pmc/articles/PMC8107075/ /pubmed/33761100 http://dx.doi.org/10.1007/s12325-021-01669-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Review Cataldi, Mauro Citro, Vincenzo Resnati, Chiara Manco, Federica Tarantino, Giovanni New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants |
title | New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants |
title_full | New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants |
title_fullStr | New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants |
title_full_unstemmed | New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants |
title_short | New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants |
title_sort | new avenues for treatment and prevention of drug-induced steatosis and steatohepatitis: much more than antioxidants |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107075/ https://www.ncbi.nlm.nih.gov/pubmed/33761100 http://dx.doi.org/10.1007/s12325-021-01669-y |
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