Inflammatory Stress and Idiosyncratic Hepatotoxicity: Hints from Animal Models

Deng, Xiaheng; Luyendyk, James P.; Ganey, Patricia E.; Roth, Robert A.

doi:10.1124/pr.109.001727

Cited by 126 publications

(111 citation statements)

References 241 publications

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“…46 The second mechanism involving idiosyncratic DILI is limited by the lack of experimental animal models, although the last few years have advanced our understanding of idiosyncratic DILI by studies on murine models. 47,48 One of the important concepts in idiosyncratic DILI is the inflammatory stress hypothesis, wherein bacterial lipopolysaccharide (LPS) released as a result of inflammation, in conjunction with drug metabolites has the potential to precipitate DILI. Inflammagen as a precipitant of liver injury has been described in animal models involving drugs such as diclofenac, sulindac, and trovafloxacin among others.…”

Section: Pathogenesis Of Drug-induced Hepatitismentioning

confidence: 99%

“…Inflammagen as a precipitant of liver injury has been described in animal models involving drugs such as diclofenac, sulindac, and trovafloxacin among others. 47,48 In addition there is increasing evidence of the important role of the innate and adaptive immune system through an interdependent pathway in the pathogenesis of DILI. 40,48 The liver may be considered as an immunologic organ with an important role in immune mediated pathway.…”

Section: Pathogenesis Of Drug-induced Hepatitismentioning

confidence: 99%

See 1 more Smart Citation

An Update on Drug-induced Liver Injury

Devarbhavi

2012

Journal of Clinical and Experimental Hepatology

143

101

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Section: Pathogenesis Of Drug-induced Hepatitismentioning

confidence: 99%

Section: Pathogenesis Of Drug-induced Hepatitismentioning

confidence: 99%

An Update on Drug-induced Liver Injury

Devarbhavi

2012

Journal of Clinical and Experimental Hepatology

143

101

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“…Sci., 15 (3): 116-123, 2015 Certain drugs may cause liver injury when introduced even within the therapeutic ranges. Hepatotoxicity may result not only from direct toxicity of the primary compound but also from a reactive metabolite or from an immunologically mediated response affecting hepatocytes, biliary epithelial cells and/or liver vasculature (Saukkonen et al, 2006;Deng et al, 2009). The hepatotoxic response elicited by chemical agent depends on toxicant concentration which may be parent compound, toxic metabolite, differential expression of enzymes and concentration gradient of cofactors in blood across the acinus (Kedderis, 1996).…”

Section: Introductionmentioning

confidence: 99%

Effect of Methanol Extract of Abrus precatorius Leaves on Male Wistar Albino Rats Induced Liver Damage using Carbon Tetrachloride (CCl4)

Uroko¹,

Adeyi²,

Hadiza³

et al. 2015

J. of Biological Sciences

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A B S T R A C T This study evaluates qualitative and quantitative phytochemical properties ofAbrus precatorius leaves. The vitamins and therapeutic effect of methanol extract against tetrachloride (CCl 4 ) induced liver damage in male Wistar albino rats. The results of phytochemical and vitamins indicates richness in saponins, tannins, alkaloids and flavonoids with value 30.05±0.22%, while vitamins such as thiamine, riboflavin, niacin, antioxidant and vitamins A, C and E was quantified. The liver damage was observed in the animals with significant increase in ALT, AST and ALP following the in traperitoneal administration of CCl 4 . The methanol extract caused significant decrease (p<0.05) in the activities of these enzymes in the treated animals relative to positive control that received CCl 4 but were not treated. The extract showed potentials to mopping-up of free radicals generated by CCl 4 . The extract reduced lipid peroxidation in concentration dependent manner. The findings suggests that the extract have the capacity to improving liver functions and liver regeneration at high concentration. The extracts are safe for consumption, abundant phytochemicals and antioxidant vitamins could offer reasonable protections against oxidative stress.

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“…16,17 Drug-inflammation interaction is an intriguing model for investigating the mechanisms of drug-induced liver injury. 18,19 It has been reported that a modest and noninjurious inflammation interacts with a small dose of drugs and induces hepatotoxicity. 20,21 Bacterial lipopolysaccharide (LPS, Endotoxin) is widely applied in this model to induce a modest inflammation.…”

Section: Introductionmentioning

confidence: 99%