Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways

Liu, Fu-Chao; Lee, Hung-Chen; Liao, Chia-Chih; Li, Allen H.; Yu, Huang-Ping

doi:10.1155/2016/1952947

Cited by 19 publications

(13 citation statements)

References 42 publications

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“…In our experiment, the PA- and PH-induced hepatic oxidative damage was evidenced by the liver histopathological findings and the significant increased hepatic levels of MDA and NO and serum levels of 8-OH-Gua, with significant decreased hepatic GSH and total thiols among PA-only and PH-only treated groups when compared with the controls. These findings were in agreement with many studies [ 29 – 33 ].…”

Section: Discussionsupporting

confidence: 94%

Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats

Saleem

El‐Maali

Hassan

et al. 2018

International Journal of Hepatology

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Background and Aims Both paracetamol (PA) and phenacetin (PH) are analgesic and antipyretic agents. Part of phenacetin therapeutic activity is attributed to its metabolism into paracetamol. Paracetamol causes direct hepatic oxidative stress damage. The present study aimed to investigate the possible damaging effects of both PA and PH, when used in therapeutic doses, on rat liver and to compare the antioxidant and hepatoprotective effects of N-acetylcysteine (NAC), N-acetyl-methionine (NAM), and N-acetylglucosamine (NAG) against PA- or PH-induced hepatic damage. Methods 90 male Wistar albino rats (120-140 gm) were undertaken, categorized randomly into 9 groups of 10 rats each, and administered by gavage for 2 weeks with DMSO 1% (controls), PA, PA+NAC, PA+NAM, PA+NAG, PH, PH+NAC, PH+NAM, and PH+NAG. Biochemical assays of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), total thiols, and alpha-fetoprotein (AFP) in liver homogenates and serum assays of ALT, AST, 8-hydroxy guanine (8-OH-Gua), and AFP were done. Also histopathological examinations of liver tissues in various groups were done. Results PA and PH cause significant increase in hepatic levels of MDA, NO, and AFP and serum ALT, AST, and 8-OH-Gua levels, with significant decrease in hepatic GSH and total thiols. NAG and NAC significantly improve the PA- and PH-induced hepatic and blood, biochemical, and histopathological disturbances, respectively. Conclusions Both PA and PH induce oxidative stress in rat liver within their therapeutic doses. NAG and NAC in pharmacological doses can antagonize the oxidative damaging effect of both PA and PH.

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Section: Discussionsupporting

confidence: 94%

Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats

Saleem

El‐Maali

Hassan

et al. 2018

International Journal of Hepatology

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“…Some researchers have suggested that ERK is one of the most important mediators in liver injury. The study by Fu et al showed that acetaminophen-induced liver injury was ameliorated by suppressing the JNK/ERK pathway [ 51 ]. Liu et al found that the ERK pathway can regulate matrix metalloproteinase-1 induction in hepatic stellate cells [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Quercetin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy by Inhibiting ERK/NF-κB Pathway

Dai

et al. 2017

Gastroenterology Research and Practice

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Background Hepatic ischemia reperfusion (IR) injury is a common phenomenon in transplantation or trauma. The aim of the present study was to determine the protective effect of quercetin (QE) on hepatic IR injury via the ERK/NF-κB pathway. Methods Mice were randomized into the sham, IR, QE100 + IR, and QE200 + IR groups. Quercetin was administered intragastrically daily at two doses (100 mg/kg and 200 mg/kg) for 5 days prior to IR injury. The expression levels of liver enzymes, inflammatory cytokines, and other marker proteins were determined at 2, 8, and 24 hours after IR. And they were compared among these groups. Results Compared with the IR group, the treatment of QE reduced the release of cytokines, leading to inhibition of apoptosis and autophagy via downregulation of the ERK/NF-κB pathway in this model of hepatic IR injury. Conclusion Apoptosis and autophagy caused by hepatic IR injury were inhibited by QE following a reduction in the release of inflammatory cytokines, and the relationship between the two may be associated with inactivation of the ERK/NF-κB pathway.

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“…By a gene ontology and KEGG analysis of co‐expressed mRNA, we found that lncRNA might maintain hepatic homeostasis and the damage repair process through protein processing in the endoplasmic reticulum, MAPK, and PPAR signaling pathway. Several studies have reported that the MAPK and PPAR signaling pathway play important regulatory roles in the progression of AILI . The endoplasmic reticulum protein synthesis pathway may be associated with endoplasmic reticulum stress, which can be induced by various pathophysiological situations including ischemic injury, viral infection, drug‐induced liver injury and metabolic diseases, and lead to cell apoptosis …”

Section: Discussionmentioning

confidence: 99%

Long non‐coding RNAs play regulatory roles in acetaminophen‐induced liver injury

Zheng

Tang

Yang

et al. 2019

J of Digest Diseases

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Objective: To explore the expression profile and role of hepatic long non-coding RNA (lncRNA) in acetaminophen-induced liver injury mouse model by analyzing lncRNA-mRNA co-expression.Methods: Serum aminotransferase, liver pathology and inflammatory cells were analyzed in mice model at different time points after treated with acetaminophen 300 mg/kg. High-throughput RNA sequencing was performed to investigate hepatic expression profiles of messenger RNA (mRNA) and lncRNA. The relationship between the lncRNA and mRNA was delineated by the co-expression network using Cytoscape software. Differential mRNAs co-expressed with lncRNAs were analyzed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment. Differential mRNAs and lncRNAs were selected for quantitative reverse transcription polymerase chain reaction validation, and the conservation of lncRNA between human and mouse was analyzed.Results: Liver injury was more severe at 24 hours than at 6 hours. There was a substantial infiltration of monocytes instead of neutrophil and Kupffer cells at 24 hours compared with 6 hours. The mRNAs co-expressed with the differential lncRNAs at 24 vs 6 hours were mainly enriched in protein processing in endoplasmic reticulum, MAPK and PPAR signaling pathways. The co-expression network delineated with four lncRNAs and 94 mRNAs presented the core position of lncRNA in the network.A conservation analysis indicated that four differential mouse lncRNAs (NONMMUT023651.2, NONMMUT029382.2, NONMMUT029383.2 and NON-MMUT102053.1) could all be mapped to the relevant human lncRNAs.Conclusion: Four lncRNAs may play regulatory roles through metabolic and apoptosis-related pathways during hepatic homeostasis maintenance and repair progress. K E Y W O R D Sacetaminophen, liver, long non-coding RNA, mRNA, RNA sequencing

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Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways

Cited by 19 publications

References 42 publications

Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats

Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats

Quercetin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy by Inhibiting ERK/NF-κB Pathway

Long non‐coding RNAs play regulatory roles in acetaminophen‐induced liver injury

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