Drug-induced Liver Injury

Kleiner, David E.

doi:10.1016/j.gtc.2017.01.004

Cited by 63 publications

(19 citation statements)

References 67 publications

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“…Hepatic inflammation is a very common phenomenon in acute DILI. [54] During APAP intoxication in the liver, the resident immune cells such as Kupffer's cells, natural killer cells, and monocytes release several proinflammatory mediators and are implicated in hepatic inflammation and necrosis. [55][56][57] APAP intoxication activates liver macrophages responsible for the release of several inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Boldine treatment protects acetaminophen‐induced liver inflammation and acute hepatic necrosis in mice

Ezhilarasan

Raghunandhakumar

2021

J Biochem & Molecular Tox

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Drug‐induced liver injury (DILI) is a frequent cause responsible for acute liver failure (ALF). Acetaminophen (APAP) is a known hepatotoxin predictably causing intrinsic DILI. At high doses, APAP causes acute liver necrosis and responsible for ALF and liver transplant cases in 50% and 20% of patients, respectively, in the United States alone. Oxidative stress and glutathione depletion are implicated in APAP‐induced liver necrosis. Boldine, a plant‐derived compound is shown to have promising antioxidant potential. Therefore, this study investigates the protective effect of boldine against APAP‐induced acute hepatic necrosis in mice. A single toxic dose of APAP (300 mg/kg b.w. p.o.) was administered in overnight‐fasted mice to induce acute liver necrosis. Separately, APAP + boldine and APAP + N‐acetylcysteine (NAC) simultaneous treatments were also given. Serum transaminases and reduced glutathione, enzymic antioxidants, tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and, IL‐6 were evaluated in liver tissue. Acute APAP intoxication significantly elevated serum marker enzymes of hepatotoxicity. APAP administration increased lipid peroxidation, TNF‐α, IL‐1β, and IL‐6 protein expressions. The enzymic antioxidants and reduced glutathione levels were decreased in liver tissue of APAP intoxicated mice. Boldine and NAC simultaneous treatments prevented APAP‐induced oxidative stress, inflammation, and necrosis. The results of this study suggest the crucial role of boldine to protect against APAP induced hepatotoxicity by virtue of its antioxidant and anti‐inflammatory properties.

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Section: Discussionmentioning

confidence: 99%

Boldine treatment protects acetaminophen‐induced liver inflammation and acute hepatic necrosis in mice

Ezhilarasan

Raghunandhakumar

2021

J Biochem & Molecular Tox

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“…At the same time, the biotransformation process of the human body is mainly carried out in the liver, and thus, it is vulnerable to numerous factors (24). alcoholism, excessive drug use and viral infections can all cause acute hepatic damage (25,26). D-GalN can cause hepatic degeneration and necrosis through competitive depletion of uridine phosphate.…”

Section: Discussionmentioning

confidence: 99%

SERP1 reduces inchoate acute hepatic injury through regulation of endoplasmic reticulum stress via the GSK3β/β‑catenin/TCF/LEF signaling pathway

et al. 2022

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The liver is a crucial digestive organ of humans and in charge of detoxification. Acute hepatic injury is an aggressive type of hepatic disease and its harmful effect cannot be ignored. The present study examined the role and mechanism of stress-associated endoplasmic reticulum protein 1 (SERP1) in acute hepatic injury. Mice were injected intraperitoneally with D-galactosamine/lipopolysaccharide (LPS) and rat hepatocytes were induced by LPS to establish an acute hepatic injury model. Tissue lesions were observed by H&E staining, and biomarkers of hepatic injury in the serum were examined. Western blotting, immunohistochemistry and reverse transcription-quantitative PCR were performed to assess SERP1 expression in tissues and hepatocytes. A SERP1 overexpression plasmid was constructed to evaluate the role of SERP1 in inflammation, apoptosis, endoplasmic reticulum stress (ERS) and the GSK3β/β-catenin/T-cell factor (TCF)/lymphoid enhancing factor (LEF) signaling pathway. In addition, a GSK3β overexpression plasmid was constructed to investigate the role of GSK3β/β-catenin signal activation. Additionally, the present study investigated whether SERP1 regulated the endoplasmic reticulum via this pathway. In the present study, reliable animal and cellular hepatic injury models were established and verified. SERP1 overexpression reduced the expression of inflammatory factors, apoptosis-related proteins and ERS-related proteins, as well as the expression of proteins related to GSK3β/β-catenin/TCF/LEF signaling pathways. A GSK3β overexpression plasmid was constructed and it was revealed that GSK3β overexpression could reverse the effects of SERP1 overexpression in aforementioned aspects. This suggested that the activation of the GSK3β/β-catenin/TCF/LEF signaling pathway may be required for the regulation of SERP1. In conclusion, SERP1 regulated ERS via the GSK3β/β-catenin/TCF/LEF signaling pathway, thereby reducing inchoate acute hepatic injury.

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“…[8] If the metabolite is destructive, it will cause damage to the hepatocytes around the central vein. [9]…”

Section: Discussionmentioning

confidence: 99%

Sub-chronic toxicity of Garcinia atroviridis Griff Fruit's ethanol extract on Wistar rats (Ratus norvegicus)

Milanda

Safrudin

Samudra

et al. 2019

J Adv Pharm Technol Res

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Garcinia atroviridis Griff. (GA) is a tropical fruit that commonly used as a traditional medicine to this day. This study was conducted to determine the sub-chronic toxicity effect of GA fruits ethanol extract on body weight, clinical hematology and biochemical parameters, and organ's histopathology. This study is an experimental research by oral treatments for 90 days with completely randomized design. The treatment group consists of five classes. Each class was given the treatment with a dosage of 50 mg/kg BW, 200 mg/kg BW, 800 mg/kg BW and satellite group with 2% PGA, or 800 mg/kgBW. Based on ANOVA and advanced Tukey test results using SPSS, the hematological parameters such as mean corpuscular volume, mean corpuscular hemoglobin concentration, and white blood cell had significant differences with the control group. In the biochemical parameters, the serum glutamic-oxaloacetic transaminase values and triglycerides (in male rats), serum glutamic-pyruvic transaminase and creatinine (in female rats) had significant differences with the control group. In conclusion, GA fruits ethanol extract is safe and non toxic to body weight, clinical hematology and biochemical parameters, and histopathology of ten organs.

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Drug-induced Liver Injury

Cited by 63 publications

References 67 publications

Boldine treatment protects acetaminophen‐induced liver inflammation and acute hepatic necrosis in mice

Boldine treatment protects acetaminophen‐induced liver inflammation and acute hepatic necrosis in mice

SERP1 reduces inchoate acute hepatic injury through regulation of endoplasmic reticulum stress via the GSK3β/β‑catenin/TCF/LEF signaling pathway

Sub-chronic toxicity of Garcinia atroviridis Griff Fruit's ethanol extract on Wistar rats (Ratus norvegicus)

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