Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes

Su, Qiang; Kuang, Wei; Wei-yi, Hao; Liang, Jing; Wu, Liang; Tang, Chunmei; Wang, Yali; Liu, Tao

doi:10.1155/2021/8086253

Cited by 24 publications

(22 citation statements)

References 45 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Control experiments with macrophages from PXR −/− or NLRP3 −/− mice underlined that PXR is needed for NLRP3 activation and cytokine release [61]. Similar results had been obtained in vascular endothelial cells [62] and liver cells or tissue [63].…”

Section: Role Of Pxr In Health and Diseasesupporting

confidence: 70%

Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning

Rigalli

Theile

Nilles

et al. 2021

Cells

View full text Add to dashboard Cite

The pregnane X receptor (PXR, NR1I2) is a nuclear receptor which exerts its regulatory function by heterodimerization with the retinoid-X-receptor α (RXRα, NR2B1) and binding to the promoter and enhancer regions of diverse target genes. PXR is involved in the regulation of drug metabolism and excretion, metabolic and immunological functions and cancer pathogenesis. PXR activity is strongly regulated by the association with coactivator and corepressor proteins. Coactivator proteins exhibit histone acetyltransferase or histone methyltransferase activity or associate with proteins having one of these activities, thus promoting chromatin decondensation and activation of the gene expression. On the contrary, corepressor proteins promote histone deacetylation and therefore favor chromatin condensation and repression of the gene expression. Several studies pointed to clear cell- and ligand-specific differences in the activation of PXR. In this article, we will review the critical role of coactivator and corepressor proteins as molecular determinants of the specificity of PXR-mediated effects. As already known for other nuclear receptors, understanding the complex mechanism of PXR activation in each cell type and under particular physiological and pathophysiological conditions may lead to the development of selective modulators with therapeutic potential.

show abstract

Section: Role Of Pxr In Health and Diseasesupporting

confidence: 70%

Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning

Rigalli

Theile

Nilles

et al. 2021

Cells

View full text Add to dashboard Cite

show abstract

“…Haplotype, as a relatively common data type, plays an essential role in the study of genetic epidemiology, including the association analyses for finding and locating disease-causing genes [ 19 ]. A single nucleotide polymorphisms (SNPs) site provides extremely limited information for complex diseases because of the interactions among multiple sites [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Study on the associations between liver damage and antituberculosis drug rifampicin and relative metabolic enzyme gene polymorphisms

Liu

et al. 2021

Bioengineered

Self Cite

View full text Add to dashboard Cite

The occurrence of antituberculosis drug-induced liver injury affects the effectiveness of antituberculosis treatments. Understanding the mechanism and risk factors of such liver injury may improve the outcomes of those patients who received antituberculosis treatments. In this study, 2,255 pulmonary tuberculosis patients were included. Their medical records were reviewed, questionnaire surveys, liver function tests at the end of February (including patients with uncomfortable symptoms during the intensive treatment period), and blood samples were saved. Afterward, cases of liver damage were determined using Chinese liver damage criteria. The genotype of all participants was determined using the PCR-LDR method. Finally, the association between genetic polymorphism and ATB-DILI susceptibility was assessed using the univariate Logistic regression models. Among the 2,255 tuberculosis patients who received rifampicin, 612 (27.1%) had antituberculosis drug-induced liver injury. We observed higher proportions of older age, male, and lower levels of AST, ALT, and TBil among patients with liver injury. Results of univariate of logistic regression models showed that patients with CYP2C19 were more likely to have liver injury compared with no such genotypes patients (all P < 0.05). Patients with tuberculosis with older age and genetic polymorphism of CYP3A4, CYP2C9, and CYP2C19 who received long-term rifampicin treatment were more likely to have antituberculosis drug-induced liver injury. It is important for healthcare providers to carefully evaluate and monitor rifampicin use for these patients.

show abstract

“…These metabolites were suggested to be responsible for INH‐induced injury to the liver (Metushi et al., 2016; Nahid et al., 2016). INH‐mediated oxidative damage occurs mainly due to the formation of ROS, which acting as LPO stimulators and as a source of hepatocellular cell membrane destruction and damage (Hassan et al., 2015; Su et al., 2021). In this study, INH + DDS simultaneous administration induces LPO, and there was a concomitant decrease observed in the activities of intracellular antioxidants such as SOD, CAT, and GSH in liver tissue of rats indicating the onset of oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Lagerstroemia speciosa (L.) Pers., ethanolic extract attenuates simultaneously administered isoniazid‐ and dapsone‐induced hepatotoxicity in rats

Singh

Ezhilarasan

2021

J Food Biochem

View full text Add to dashboard Cite

Herbal tea of Lagerstroemia speciosa Pers., commonly known as banaba, has been traditionally used to treat various ailments including diabetes and obesity due to its antioxidant and anti‐inflammatory efficacies. Drug‐induced liver injury is a common cause of acute liver failure. Isoniazid (INH) is used as the first‐line treatment for tuberculosis; clinical and experimental studies have reported an abnormal liver function after INH therapy. Dapsone (DDS) is used for leprosy and other infections. This study investigates the hepatoprotective effect of ethanolic banaba leaves extract (EBLE) against simultaneously administered INH‐ and DDS‐induced hepatotoxicity in rats. DDS (30 mg/kg, i.p.) and INH (50 mg/kg. p.o.) were administered simultaneously for 30 days. In separate groups, rats were posttreated orally with EBLE (500 mg/kg) and silymarin (100 mg/kg) for 30 days after INH + DDS administration. The marker enzymes of hepatotoxicity, oxidative stress markers, inflammatory markers, and histopathology were done. Simultaneous administration of INH‐ and DDS‐induced significant elevation of marker enzymes of hepatotoxicity in the serum. This treatment also increased lipid peroxidation and pro‐inflammatory markers (tumor necrosis factor alpha, transforming growth factor beta, and nuclear factor kappa B) expressions and decreased intracellular antioxidants such as superoxide dismutase, catalase, and glutathione in the liver tissue. All these abnormalities were significantly mitigated after EBLE and SIL posttreatments. The results of this study suggest that EBLE and silymarin can be protective against INH + DDS‐induced hepatotoxicity. Practical applications Herbal tea contain Lagerstroemia speciosa leaves are used in several Southeast Asian countries due to its rich antioxidant and inflammatory properties. This study showed the hepatoprotective efficacy of L. speciosa ethanolic extract against simultaneously administered dapsone‐ and isoniazid‐induced hepatotoxicity in rats. L. speciosa administration was found to decrease dapsone‐ and isoniazid‐induced oxidative stress and hepatic inflammation. L. speciosa herbal tea can reduce drug‐induced hepatic complications as it contains phytochemicals such as corosolic acid, gallic acid, ellagic acid and berberine and are implicated for its hepatoprotective effect. Therefore, L. speciosa extract can be used for drug‐induced liver injury.

show abstract

Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes

Cited by 24 publications

References 45 publications

Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning

Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning

Study on the associations between liver damage and antituberculosis drug rifampicin and relative metabolic enzyme gene polymorphisms

Lagerstroemia speciosa (L.) Pers., ethanolic extract attenuates simultaneously administered isoniazid‐ and dapsone‐induced hepatotoxicity in rats

Contact Info

Product

Resources

About