In the livers of rats treated with thioacetamide for 28 days
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE43066 | GEO | 2012/12/21
SECONDARY ACCESSION(S): PRJNA184301
REPOSITORIES: GEO
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Project description:To clarify the regulatory molecular mechanisms behind cell cycle aberrations related to the early stages of hepatocarcinogenesis. We investigated the early stage of hepatocarcinogenesis using global expression analyses. Livers from rats treated with thioacetamide were subjected to microarray analysis. Results were compared with livers from rats untreated controls (n = 4 animals/group).
2012-12-21 | E-GEOD-43066 | biostudies-arrayexpress
Project description:Thioacetamide (TAA) was developed as a pesticide; however, it was soon found to cause hepatic and renal toxicity. To evaluate target organ interactions during hepatotoxicity, we compared gene expression profiles in the liver and kidney after TAA treatment. Sprague-Dawley rats were treated daily with oral TAA and then sacrificed, and their tissues were evaluated for acute toxicity (30 and 100 mg/kg bw/day), 7-day (15 and 50 mg/kg bw/day), and 4-week repeated-dose toxicity (10 and 30 mg/kg). After the 4-week repeated toxicity study, total RNA was extracted from the liver and kidneys, and microarray analysis was performed. Differentially expressed genes were selected based on fold change and significance, and gene functions were analyzed using ingenuity pathway analysis. Microarray analysis showed that significantly regulated genes were involved in liver hyperplasia, renal tubule injury, and kidney failure in the TAA-treated group. Commonly regulated genes in the liver or kidney were associated with xenobiotic metabolism, lipid metabolism, and oxidative stress. We revealed changes in the molecular pathways of the target organs in response to TAA and provided information on candidate genes that can indicate TAA-induced toxicity. These results may help elucidate the underlying mechanisms of target organ interactions during TAA-induced hepatotoxicity.Supplementary informationThe online version contains supplementary material available at 10.1007/s43188-022-00156-y.
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Project description:AID is an intrinsic DNA mutator enzyme and contributes to tumorigenesis through the accumulation of genetic aberrations. To examine whether mutagenesis induced by AID during inflammation-associated hepatocarcinogenesis depends on the transcriptional levels of the target genes, we performed the gene expression profiling of liver tissues from AID transgenic mice and wild-type mice with and without thioacetamide treatment.
2015-07-10 | GSE62878 | GEO
Project description:AID is an intrinsic DNA mutator enzyme and contributes to tumorigenesis through the accumulation of genetic aberrations. To examine whether mutagenesis induced by AID during inflammation-associated hepatocarcinogenesis depends on the transcriptional levels of the target genes, we performed the gene expression profiling of liver tissues from AID transgenic mice and wild-type mice with and without thioacetamide treatment. AID transgenic mice and wild-type mice were administered with thioacetamide in drinking water for 6 months, and the gene expression levels of their livers are compared.
2015-07-10 | E-GEOD-62878 | biostudies-arrayexpress
Project description:Environmental chemicals exposure are one of the primary factors for liver toxicity and hepatocarcinoma. Thioacetamide (TAA) is a well-known hepatotoxicant and could be a liver carcinogen in humans.The discovery of early and sensitive biomarkers in liver injury and tumor progression could improve cancer diagnosis, prognosis, and management. In the present study, we studied the dynamic changes in microRNAs (miRNAs) expression and explored the potential mechanistic role of miRNAs in rat liver treated with TAA at multiple doses and time points. Sprague-Dawley rats were administrated with TAA at three doses [low (4.5 mg/kg), middle (15mg/kg) and high (45mg/kg)] and four repeated treatment durations (3-, 7-, 14- and 28-days). Expressions of miRNAs in livers were profiled using next generation sequencing and analyzed. Overall, 330 unique differentially expressed miRNAs (DEMs) were identified in the entire TAA-treatment course. Of these, 129 DEMs were found significantly enriched for the “liver cancer” annotation. These results were further complemented by pathway analysis in which “Molecular Mechanisms of Cancer”, “p53-”, “TGF-β-”, “MAPK-” and “Wnt-signaling” were significantly enriched in most TAA-treatment conditions. Two miRNAs (rno-miR-34a-5p and rno-miR-455-3p) out of 48 DEMs (common across all the treatment conditions) were identified to be early and sensitive biomarkers for TAA-induced hepatocarcinogenicity. Upregulation of rno-miR-34a-5p was further confirmed by qPCR. These findings reveal the critical role of miRNAs in the mechanisms underlying hepatocarcinogenesis and potential application for human risk assessment. Most importantly, rno-miR-34a-5p is the most suitable early and sensitive biomarker for TAA-induced hepatocarcinogenesis due to its consistent elevation during the entire treatment course.
2017-06-23 | GSE87446 | GEO
Project description:Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.
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Project description:BackgroundThe study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food and food contact materials.ResultsAgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP). The AgNPs remained stable throughout the duration of the 28-day oral toxicity study in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of AgNPs. Besides the intestinal system, the largest silver concentrations were detected in the liver and kidneys. Silver was also found in the lungs and brain. Autometallographic (AMG) staining revealed a similar cellular localization of silver in ileum, liver, and kidney tissue in rats exposed to AgNPs or AgAc. Using transmission electron microscopy (TEM), nanosized granules were detected in the ileum of animals exposed to AgNPs or AgAc and were mainly located in the basal lamina of the ileal epithelium and in lysosomes of macrophages within the lamina propria. Using energy dispersive x-ray spectroscopy it was shown that the granules in lysosomes consisted of silver, selenium, and sulfur for both AgNP and AgAc exposed rats. The diameter of the deposited granules was in the same size range as that of the administered AgNPs. No silver granules were detected by TEM in the liver.ConclusionsThe results of the present study demonstrate that the organ distribution of silver was similar when AgNPs or AgAc were administered orally to rats. The presence of silver granules containing selenium and sulfur in the intestinal wall of rats exposed to either of the silver forms suggests a common mechanism of their formation. Additional studies however, are needed to gain further insight into the underlying mechanisms of the granule formation, and to clarify whether AgNPs dissolve in the gastrointestinal system and/or become absorbed and translocate as intact nanoparticles to organs and tissues.
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Project description:Cardiomyopathy in type 1 diabetic patients is characterized by early onset diastolic and late onset systolic dysfunction. The mechanism underlying development of diastolic and systolic dysfunction in diabetes remains unknown. We used microarrays to detail the ventricle gene expression changes that underly development of diabetic cardiomyopathy. We identified distinct classes of up-regulated genes during this process. Keywords: disease state analysis, time course
2006-05-08 | GSE4745 | GEO
Project description:Acute liver failure (ALF) is a life-threatening disorder of liver function. Kynurenic acid (KYNA), a tryptophan metabolite formed along the kynurenine metabolic pathway, possesses anti-inflammatory and antioxidant properties. Its presence in food and its potential role in the digestive system was recently reported. The aim of this study was to define the effect of KYNA on liver failure. The Wistar rat model of thioacetamide-induced liver injury was used. Morphological and biochemical analyses as well as the measurement of KYNA content in liver and hepatoprotective herbal remedies were conducted. The significant attenuation of morphological disturbances and aspartate and alanine transaminase activities, decrease of myeloperoxidase and tumor necrosis factor-?, and elevation of interleukin-10 levels indicating the protective effect of KYNA in thioacetamide (TAA) - induced liver injury were discovered. In conclusion, the hepatoprotective role of KYNA in an animal model of liver failure was documented and the use of KYNA in the treatment of ALF was suggested.
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Project description:Certain bioactive peptides are reported to be able to alleviate hepatic fibrosis. Our previous work has confirmed the hepatoprotective effect of corn peptides (CPs) that are prepared from a high protein by-product, corn gluten meal, on acute liver injury in an animal model. However, the antifibrotic activity of CPs remained to be elucidated. In this study, the hepatoprotective effect of CPs on thioacetamide (TAA)-induced liver fibrosis was tested. Results showed that CPs (100 mg/kg body weight) significantly decreased the levels of alanine transaminase/aspartate transaminase, laminin, type IV collagen, and type III collagen in serum and increased the serum albumin levels and total antioxidant capacity. Additionally, with CP treatment (100 mg/kg body weight), a significant decrease was observed in the levels of malondialdehyde, nitric oxide, hydroxyproline, transforming growth factor ?1, and lactate dehydrogenase activity as well as the liver index, while the activity of superoxidedismutase was significantly increased in livers. The histological and morphological analysis showed that the hepatocyte structure in CP-treated rats was superior to that of TAA-injured rats, and inflammation and fibrosis were also ameliorated. Therefore, CPs can be used as an option for prevention and adjuvant therapy of liver fibrosis.
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