Thioacetamide

Mehendale, Harihara M.

doi:10.1016/b978-0-08-046884-6.01029-0

Cited by 4 publications

(1 citation statement)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hepatotoxic properties of TAA in mice and rats induces oxidative stress resulting first in formation of intracellular lipid deposits in the liver parenchymal cells (hepatocyte ballooning), and later leading to HEPs damage and necrosis [ 62 ]. Bioactivation of TAA into its hepatotoxic counterpart, TASO 2 [ 63 ], requires proteins from the cytochrome p450 complex, functional orthologs for many of which exist in zebrafish, including proteins with > 44.87% sequence similarity to CYP2E1, the protein thought to be directly responsible for TAA metabolism in humans [ 64 ]. Moreover, CYP2E1 function was reproduced in zebrafish tissue homogenates, albeit without identifying the specific enzyme responsible for the process [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift

et al. 2021

View full text Add to dashboard Cite

Background Liver fibrosis is a wound-healing response to tissue injury and inflammation hallmarked by the extracellular matrix (ECM) protein deposition in the liver parenchyma and tissue remodelling. Different cell types of the liver are known to play distinct roles in liver injury response. Hepatocytes and liver endothelial cells receive molecular signals indicating tissue injury and activate hepatic stellate cells which produce ECM proteins upon their activation. Despite the growing knowledge on the molecular mechanism underlying hepatic fibrosis in general, the cell-type-specific gene regulatory network associated with the initial response to hepatotoxic injury is still poorly characterized. Results In this study, we used thioacetamide (TAA) to induce hepatic injury in adult zebrafish. We isolated three major liver cell types - hepatocytes, endothelial cells and hepatic stellate cells - and identified cell-type-specific chromatin accessibility and transcriptional changes in an early stage of liver injury. We found that TAA induced transcriptional shifts in all three cell types hallmarked by significant alterations in the expression of genes related to fatty acid and carbohydrate metabolism, as well as immune response-associated and vascular-specific genes. Interestingly, liver endothelial cells exhibit the most pronounced response to liver injury at the transcriptome and chromatin level, hallmarked by the loss of their angiogenic phenotype. Conclusion Our results uncovered cell-type-specific transcriptome and epigenome responses to early stage liver injury, which provide valuable insights into understanding the molecular mechanism implicated in the early response of the liver to pro-fibrotic signals.

show abstract

Section: Discussionmentioning

confidence: 99%

Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift

et al. 2021

View full text Add to dashboard Cite

show abstract

Vanillin attenuates thioacetamide‐induced renal assault by direct and indirect mediation of the TGFβ, ERK and Smad signalling pathways in rats

Metwaly

El-Eraky

Ibrahim

et al. 2022

Cell Biochemistry & Function

View full text Add to dashboard Cite

Inflammation and fibrosis are two pathological features of chronic kidney disease (CKD). Renal fibrosis is considered to be one of the most important conditions, as it may be the result of excessive extracellular matrix protein production and deposition, or prolonged exposure to nephrotoxic substances or drugs. Unfortunately, no suitable therapies or medications are currently available to prevent renal fibrosis. We conducted this study for the evaluation of the protective potential of vanillin by reversing TAA (250 mg/kg TAA for 6 weeks) induced renal injury in rats. The concentrations of the proteins tumour necrosis factor alpha (TNFα), interleukin‐6 (IL‐6), extracellular signal regulated kinase 1/2 (Erk1/2), and transforming growth factor beta‐1 (TGF‐β1) in kidney tissues were assessed using ELISA. Kidney Injury Molecule‐1 (KIM‐1) and mothers against decapentaplegic homologue 2, 3 (SMAD 2, 3) expressions were evaluated using real time PCR. We also estimated the expression of α‐smooth muscle actin (α‐SMA) using immunohistochemistry. Treatment with vanillin (100 mg/kg) significantly ameliorated kidney Injury and improved the kidney function. Vanillin treatment also significantly decreased the malondialdehyde (MDA) content, and elevated glutathione peroxidase (GPx) and catalase (CAT) activities in kidney tissues. Vanillin also reduced α‐SMA renal expression and TNFα, IL‐6, TGF‐β1, and Erk1/2 renal levels. Vanillin significantly decreased the expression of the genes encoding KIM‐1 and SMAD 2, 3 and ameliorated histological abnormalities in kidney architecture. Our molecular docking findings showed that vanillin has a good binding mode inside TGF‐β type I receptors (ALK5) biding site.

show abstract

Protective impact of Spirulina platensis against γ-irradiation and thioacetamide-induced nephrotoxicity in rats mediated by regulation of micro-RNA 1 and micro-RNA 146a

Salem

Ismail

2021

Toxicology Research

View full text Add to dashboard Cite

Chronic kidney disease develops popular and medical health problems, especially in developing countries. The objective of this study is to investigate the protective mechanism of Spirulina platensis against γ-irradiation (R) and/or thioacetamide (TAA)-induced nephrotoxicity in rats. Rats intoxicated with R or TAA showed alterations in kidney function markers (urea, creatinine, albumin, and total protein contents), oxidative stress markers (malondialdehyde, reduced glutathione), antioxidant enzymes (superoxide dismutase, catalase), and several inflammatory markers (including, the high-sensitivity C-reactive protein, hypoxia-inducible factor-1 alpha, tumor necrosis factor-alpha, interferon-gamma, some interleukins, and nuclear factor-kappa B). Rats also acquired apoptosis, evinced by high caspase-3 efficacy. This nephrotoxicity mediated by upregulation of the messenger RNA (mRNA) gene expression of the autophagy markers: Beclin-1, microtubule-associated protein LC3, p62 binding protein, immunoglobulin G receptor Fcγ receptor (FcγR), micro-RNA-1 (miR-1), protein expression of phospho-adenosine monophosphate-activated protein kinase, and phospho-mammalian target of rapamycin, along with downregulation of miR-146a mRNA gene expression and alteration of calcium and iron levels. The combined treatment R/TAA enhanced the observed oxidative stress, inflammation, apoptosis, and autophagy that mediated by higher upregulation of miR-1 and downregulation of miR-146a mRNA gene expression. Spirulina platensis administration exhibited a nephroprotective impact on R, TAA, and R/TAA toxicities via regulating miR-1 and miR-146a mRNA gene expression that monitored adenosine monophosphate-activated protein kinase/mammalian target of rapamycin signaling.

show abstract

Thioacetamide

Cited by 4 publications

References 64 publications

Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift

Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift

Vanillin attenuates thioacetamide‐induced renal assault by direct and indirect mediation of the TGFβ, ERK and Smad signalling pathways in rats

Protective impact of Spirulina platensis against γ-irradiation and thioacetamide-induced nephrotoxicity in rats mediated by regulation of micro-RNA 1 and micro-RNA 146a

Contact Info

Product

Resources

About