Mechanisms of Drug-Induced Liver Disease

Gunawan, Basuki; Kaplowitz, Neil

doi:10.1016/j.cld.2007.06.001

Cited by 145 publications

(86 citation statements)

References 106 publications

(162 reference statements)

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“…25,26 Detailed reviews focusing on pathogenesis and mechanisms of druginduced liver injury are available elsewhere. 10,19,20,27 Liver toxicity caused by antiretroviral therapy can be inflicted through several mechanisms. The pathogenesis often remains enigmatic.…”

Section: Mechanisms Of Haart-related Hepatotoxicitymentioning

confidence: 99%

Clinical Syndromes and Consequences of Antiretroviral-Related Hepatotoxicity5, 1, 3

Núñez

2010

Hepatology

160

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Highly active antiretroviral therapy (HAART)-related hepatotoxicity complicates the management of patients infected with human immunodeficiency virus (HIV), increases medical costs, alters the prescription patterns, and affects the guideline recommendations. Among the clinical consequences derived from HAART-related liver toxicity, hypersensitivity reactions and lactic acidosis are recognized as acute events with potential to evolve into fatal cases, whereas there seems to be other syndromes not as well characterized but of equal concern as possible long-term liver complications. Belonging to the latter category of syndrome, HAART-related nonalcoholic steatohepatitis, liver fibrosis, portal hypertension, and nodular regenerative hyperplasia are discussed in this review. Updated information on liver toxicity of current antiretroviral drugs, including the most recently licensed, is provided. Management and prevention of liver toxicity among HIV-infected patients treated with HAART are reviewed as well.

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Section: Mechanisms Of Haart-related Hepatotoxicitymentioning

confidence: 99%

Clinical Syndromes and Consequences of Antiretroviral-Related Hepatotoxicity5, 1, 3

Núñez

2010

Hepatology

160

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“…W takim przypadku lek odgrywa rolę liganda dla receptorów czynnika martwicy nowotworów α (ang. tumour necrosis factor α -TNF-α) lub Fas [27,28].…”

Section: Toksyczność Adriamycynyunclassified

“…In this case, the drug serves as a ligand for the receptors of tumour necrosis factor α (TNF-α) or Fas [27,28].…”

Section: Adriamycin Toxicitymentioning

confidence: 99%

Adriamycin - efficacy and possible adverse effects

Pedrycz

Kramkowska

2016

Current Problems of Psychiatry

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Adriamycin (doxorubicin) is a chemical substance in the anthracycline class with a wide range of applications in oncology and hematology. The mechanism of action of Adriamycin is related to formation of irregular bonds between nucleobases of DNA and inhibition of key enzymes of DNA synthesis -topoisomerase I and II as well as to formation of free radicals damaging DNA.A major limitation in the drug use is associated with its adverse effects such as cardiotoxicity and hepatotoxicity. The mechanism of myocardial injury by Adriamycin is linked to an increase in oxidative stress associated with impaired mitochondrial function and structure.Cardiotoxicity of anthracyclines is classified as: acute, chronic or late (delayed). Hepatotoxicity of Adriamycin as a damage of the liver is associated with a dysfunction of this organ. Adriamycin studies have shown increased level of transaminase present in 40% of patients treated with Adriamycin. The state was transient and asymptomatic, returning to the initial level even when treatment continued.Knowledge of cancer diseases contributed to a successive creation of two improved forms of Adriamycin (doxorubicin) -nonpegylated and pegylated formulas of the drug.The mechanism of anticancer effects of liposomal Adriamycin is similar to the mechanism of conventional Adriamycin, but placement of the molecules of active substance in liposomes has significant influence on the distribution of the drug.In order to increase the distribution of the drug, a special form of liposomal Adriamycin has been created by covering the surface of the liposomes with a hydrophilic polymer -(MPEG). This process, known as pegylation, decreases the interactions between the lipid bilayer membrane and the plasma components. Pegylated form of the drug is associated with a higher incidence of acute complications.Keywords: Adriamycin, cardiotoxicity, hepatotoxicity Streszczenie Adriamycyna (doksorubicyna) jest substancją należącą do grupy antracyklin o szerokim zastosowaniu w onkologii i hematologii. Mechanizm działania Adriamycyny polega na tworzeniu nieprawidłowych wiązań pomiędzy zasadami azotowymi DNA oraz hamowaniu kluczowych enzymów syntezy DNA -topoizomerazy I i II oraz tworzeniu wolnych rodników uszkadzających DNA.Znacznym ograniczeniem w stosowaniu Adriamycyny są działania niepożądane tego leku, takie jak: kardiotoksyczność oraz hepatotoksyczność.Mechanizm uszkodzenia mięśnia sercowego przez Adriamycynę polega na wywoływaniu stresu oksydacyjnego związanego z zaburzeniami funkcji i struktury mitochondriów.Kardiotoksyczność antracyklin klasyfikowana jest, jako: ostra, przewlekła oraz późna. Hepatotoksyczność Adriamycyny, polegająca na uszkodzeniu wątroby związana jest z upośledzoną funkcją tego narządu. Badania nad Adriamycyną pokazują, że zwiększony poziom aminotransferaz występuje u do 40% pacjentów leczonych Adriamycyną, ale jest przemijający i przebiega bezobjawowo, powracający do stanu początkowego nawet przy kontynuacji leczenia.Wiedza o chorobach nowotworowych przyczyniła się do powstania...

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“…In this specific pathological condition, the injury largely remains limited to a particular zone of a liver lobule leading to a very high level of ALT, severe disturbance of liver function and finally to acute liver failure [21]. Acetaminophen, valproic acid and carbon tetrachloride can lead to zonal necrosis if taken in high doses [22].…”

Section: Necrosismentioning

confidence: 99%

Cellular and Molecular Aspects of Drug-Induced Liver Toxicity: Recent Prominent Mechanisms

Erkekoğlu¹

2015

MOJT

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Despite recent advances in drug development technologies, some drugs continue to be withdrawn from the market because of their late hepatotoxic effects. Drugs can cause liver toxicity through several molecular mechanisms, most of which need to be clarified by further research. Newly found drug-induced liver injury (DILI)-mechanisms like endoplasmic reticulum stress should also be considered while evaluating drug toxicity. New drugs launched in the market should be tested particularly for hepatotoxicity by using hepatic cell cultures and animal models continuously. Future research should target patients in the post-marketing phase in order to provide more evidence grounds to the clinical safety of potential drugs of high propensity of DILI. This review aims to draw the attention to the issue of cellular and molecular aspects of liver toxicity induced by drugs and address DILI as a potential clinical problem that needs further investigation.

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Mechanisms of Drug-Induced Liver Disease

Cited by 145 publications

References 106 publications

Clinical Syndromes and Consequences of Antiretroviral-Related Hepatotoxicity5, 1, 3

Clinical Syndromes and Consequences of Antiretroviral-Related Hepatotoxicity5, 1, 3

Adriamycin - efficacy and possible adverse effects

Cellular and Molecular Aspects of Drug-Induced Liver Toxicity: Recent Prominent Mechanisms

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