Biochemical changes in liver in acute thioacetamide intoxication

Gallagher, C. H.; Gupta, Deepak; Judah, J. D.; Rees, K. R.

doi:10.1002/path.1700720125

Cited by 130 publications

(37 citation statements)

References 12 publications

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“…Cytochrome (CY) P450 2B, 2E1 and flavin monooxygenase metabolize TAA into its toxic metabolites (30). Previous studies have identified a number of TAA-induced liver diseases, including hyperplastic liver nodules, liver cell adenomas, hepatocarcinomas, liver cirrhosis and tumors (31)(32)(33)(34)(35). In our previous study, male SD rats were administered with 300 mg/l TAA in drinking water to construct an easy and reproducible animal model recapitulating the multi-stage progression of human CCA.…”

Section: Discussionmentioning

confidence: 99%

cDNA microarray profiling of rat cholangiocarcinoma induced by thioacetamide

Yeh

Weng

Lenka

et al. 2013

Molecular Medicine Reports

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Abstract. Cholangiocarcinoma (CCA) is a malignant neoplasm affecting thousands of individuals worldwide. CCA develops through a multistep process. In the current study, an oral thioacetamide (TAA)-induced model of rat CCA was established which generates the histological progression of human CCA, particularly the mass-forming type. Seven male Sprague-Dawley rats were treated with TAA for 24 weeks to induce CCA. Following the generation of the rat CCA model, whole rat genomic oligo microarray was performed to examine gene expression profiles in CCA and non-cancerous liver samples. In brief, 10,427 genes were found to be differentially expressed (8,318 upregulated and 3,489 downregulated) in CCA compared with non-tumor liver tissue. The top 50 genes (upregulated or downregulated) were selected and their functional involvement in various pathways associated with cancer progression was analyzed, including cell proliferation, apoptosis, metabolism and the cell cycle. In addition, increased expression of CLCA3, COL1A2, DCN, GLIPr2 and NID1, and decreased expression of CYP2C7 and SLC10A1 were validated by quantitative real-time PCR. Immunohistochemical analysis was performed to determine the protein expression levels of GLIPr2 and SLC10A1. The gene expression profiling performed in this study provides a unique opportunity for understanding the carcinogenesis of TAA-induced CAA. In addition, expression profiling of a number of specific genes is likely to provide important novel biomarkers for the diagnosis of CCA and the development of novel therapeutic strategies for CCA.

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Section: Discussionmentioning

confidence: 99%

cDNA microarray profiling of rat cholangiocarcinoma induced by thioacetamide

Yeh

Weng

Lenka

et al. 2013

Molecular Medicine Reports

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“…In several tissues, compounds with local anaesthetic activity inhibit to approximately the same extent the net gain of sodium and calcium, and also the net loss of potassium, in response to a variety of excitatory or damaging agents (Gallagher et al, 1956;Rees, Sinha & Spector, 1961;Feinstein, 1963; Judah, Ahmed & McLean, 1964;Feinstein & Paimre, 1969;Chan & Quastel, 1970). The action of indomethacin on cation fluxes seems to differ from that of local anaesthetics in two respects.…”

Section: Discussionmentioning

confidence: 99%

The effects of indomethacin on calcium, sodium, potassium and magnesium fluxes in various tissues of the guinea‐pig

Northover

1972

British J Pharmacology

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Summary Isolated tissues of the guinea‐pig were bathed with Krebs solution at 37° C and subjected to 100 ms pulses of electrical stimulation for 30 min at a frequency of 0·1 or 1·0 Hz. The tissues were then dried, ashed, and the ash analysed for calcium, sodium, potassium and magnesium. Gastric smooth muscle, cardiac and skeletal muscles and brain all showed a gain of sodium and calcium and a loss of potassium in response to electrical stimulation, but there was no significant change in the magnesium content of any of these tissues. Indomethacin (0·5 mm) reduced the calcium content of unstimulated gastric smooth muscle and reduced the gain of calcium and sodium in response to electrical stimulation, but slightly increased the net loss of potassium in response to electrical stimulation. Gastric smooth muscle which had gained calcium as a result of electrical stimulation, gradually lost it again when stimulation ceased. Indomethacin (0·5 mm) hastened the net loss of calcium from previously stimulated muscle. Indomethacin (0·5 mm) failed to alter the calcium, sodium, potassium and magnesium contents of unstimulated cardiac muscle, skeletal muscle and brain. In these tissues indomethacin (0·5 mm) also failed to prevent the changes in the content of these minerals which occurred in response to electrical stimulation.

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“…Prolonged administration of TAA causes hyperplastic liver nodules, liver cell adenomas and hepatocarcinomas. Various TAA induction methods have been tried in experimental animals to produce liver cirrhosis and tumors, including intraperitoneal or subcutaneous administration [7,8] and administering toxin with food [3] or drinking water [9]. TAA is known as a potent hepatotoxicant which requires metabolic activation by missed function oxidases.…”

Section: Introductionmentioning

confidence: 99%