Mechanisms of Toxic Liver Injury

Anderson, Nora; Borlak, Jürgen

doi:10.1002/9780470516751.ch9

Cited by 4 publications

(3 citation statements)

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“…The interaction between the radical molecule and vitamin E would therefore stop the propagation of the peroxyl radical chain reaction (Packer et al 2001) and alleviate the oxidative stress response. The increase in ROS formation would explain a number of deleterious effects such as membrane damage and loss of cellular integrity (Anderson & Borlak 2007) in the liver. The injury to hepatocytes following OP pesticide intoxication would cause the release of cytosolic enzymes into blood circulation (Elhalwagy et al 2008).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Tocotrienol-Rich Fraction on Oxidative Liver Damage Induced by Fenitrothion

Jayusman

Budin²,

Taib³

et al. 2017

JSM

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Exposure to organophosphate pesticide including fenitrothion (FNT) has led to many adverse effects on human health. However, a potent antioxidant like palm oil tocotrienol-rich fraction (TRF) can reduce oxidative damage in various pathological conditions, could also reduce the adverse effects by FNT. The aim of this study was to evaluate the effect of TRF on oxidative liver damage in FNT induce hepatotoxicity in experimental rats. A total of 40 male Sprague-Dawley rats were randomly divided into four groups of 10, namely control, TRF, FNT and TRF+FNT group. TRF (200 mg/kg body weight) and FNT (20 m/kg body weight) were administered through oral gavage for 28 days. Corn oil which served as vehicle was given orally to the control group. At the end of the study period, liver and blood was taken for oxidative damage and biochemical evaluation and histological observation. TRF supplementation prevents oxidative liver damage by reducing the hepatic malondialdehyde (MDA) and protein carbonyl (PCO) level significantly. Besides, TRF also restored the endogenous antioxidants particularly reduced glutathione (GSH), glutathione peroxidase (GPx) and ferric reducing/antioxidant power (FRAP). TRF also prevent liver damage by reducing the liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The attenuation of liver damage by TRF was also showed histologically. In conclusion, TRF supplementation showed a potential in preventing oxidative liver damage in FNTtreated rats by reducing the oxidative damage and improving the antioxidant status.

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Section: Discussionmentioning

confidence: 99%

The Effect of Tocotrienol-Rich Fraction on Oxidative Liver Damage Induced by Fenitrothion

Jayusman

Budin²,

Taib³

et al. 2017

JSM

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“…During fibrosis progression, the liver shows varied regional susceptibility to injury and toxins due to architectural complexities, protein gradients, and oxygen levels (Matsuzaki et al, 1997;Heinloth et al, 2004;Anderson and Borlak, 2008). Regardless of different etiologies of liver fibrosis, HSCs become activated, proliferative, migrate to fibrotic regions, and become highly abundant in the fibrotic foci.…”

Section: Discussionmentioning

confidence: 99%

Hepatic Stellate Cell–Targeted Delivery of Hepatocyte Growth Factor Transgene via Bile Duct Infusion Enhances Its Expression at Fibrotic Foci to Regress Dimethylnitrosamine-Induced Liver Fibrosis

et al. 2013

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Liver fibrosis generates fibrotic foci with abundant activated hepatic stellate cells and excessive collagen deposition juxtaposed with healthy regions. Targeted delivery of antifibrotic therapeutics to hepatic stellate cells (HSCs) might improve treatment outcomes and reduce adverse effects on healthy tissue. We delivered the hepatocyte growth factor (HGF) gene specifically to activated hepatic stellate cells in fibrotic liver using vitamin A-coupled liposomes by retrograde intrabiliary infusion to bypass capillarized hepatic sinusoids. The antifibrotic effects of DsRed2-HGF vector encapsulated within vitamin A-coupled liposomes were validated by decreases in fibrotic markers in vitro. Fibrotic cultures transfected with the targeted transgene showed a significant decrease in fibrotic markers such as transforming growth factor-b1. In rats, dimethylnitrosamineinduced liver fibrosis is manifested by an increase in collagen deposition and severe defenestration of sinusoidal endothelial cells. The HSC-targeted transgene, administered via retrograde intrabiliary infusion in fibrotic rats, successfully reduced liver fibrosis markers alpha-smooth muscle actin and collagen, accompanied by an increase in the expression of DsRed2-HGF near the fibrotic foci. Thus, targeted delivery of HGF gene to hepatic stellate cells increased the transgene expression at the fibrotic foci and strongly enhanced its antifibrotic effects.

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“…In a subsequent 6-months chronic toxicity study the initial hepatobiliary effects were reproduced, but at the end of the study liver function recovered. Liver function in vitro at >170-fold of therapeutic C(max) levels, including cytotoxicity (LDH, MTT, ATP), transaminase activities (ALT, AST), albumin synthesis, urea and testosterone metabolism to assay for CYP monooxygenase activity [68]. Toxicogenomics has emerged as use of genome-scale mRNA expression profiling to monitor responses to adverse xenobiotic exposure.…”

Section: Toxicogenomics and Clinical Mechanismsmentioning

confidence: 99%

Toxicogenomics and cancer pathogenesis

Gupta¹,

AK²,

Boraste³

et al. 2009

Int J Genet

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Abstract-Toxicogenomics is emerging field give idea of the application of large-scale differential gene expression data to toxicology, starting to influence drug discovery and development in the pharmaceutical industry. Its future potential in cancer pathogenesis, study of poisons and poisoning and has an ancient and venerable history. Toxicogenomics is the merging of toxicology with technologies that have been developed, together with bioinformatics, to identify and quantify global gene expression changes for gene therapy. Immunotoxic processes and the development of in vitro screening assays is therefore expected to be of value for mechanistic insight into immunotoxicity and hazard identification of existing and novel compounds. Successful application of toxicogenomic approaches, such as DNA microarrays, inextricably relies on appropriate data management, the ability to extract knowledge from massive amounts of data and the availability of functional information for data interpretation. Toxicogenomics is considered a valuable tool for reducing pharmaceutical candidate attrition by facilitating earlier identification, prediction and understanding of toxicities. Pharmaco-epidemiological (toxicogenomics) data is now available for both antiepileptic drugs, evidence for human carcinogenicity. Therapeutic researches converge triad of rejuvenation, regeneration or replacement strategies that rely on self-healing processes, stem cell regeneration organ transplantation. Metastases studies usually display more genetic changes than the primary tumour. Helix-loop-helix application in translational and functional toxicogenomics transcription factors has been implicated in diverse cellular processes such as proliferation, apoptosis, differentiation, and migration.

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Mechanisms of Toxic Liver Injury

Cited by 4 publications

References 0 publications

The Effect of Tocotrienol-Rich Fraction on Oxidative Liver Damage Induced by Fenitrothion

The Effect of Tocotrienol-Rich Fraction on Oxidative Liver Damage Induced by Fenitrothion

Hepatic Stellate Cell–Targeted Delivery of Hepatocyte Growth Factor Transgene via Bile Duct Infusion Enhances Its Expression at Fibrotic Foci to Regress Dimethylnitrosamine-Induced Liver Fibrosis

Toxicogenomics and cancer pathogenesis

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