التفاصيل البيبلوغرافية
| العنوان: |
MCLR-elicited hepatic fibrosis and carcinogenic gene expression changes persist in rats with diet-induced nonalcoholic steatohepatitis through a 4-week recovery period. |
| المؤلفون: |
Arman, Tarana1 (AUTHOR), Baron, J. Allen1 (AUTHOR), Lynch, Katherine D.1 (AUTHOR), White, Laura A.2 (AUTHOR), Aldan, Johnny1 (AUTHOR), Clarke, John D.1 (AUTHOR) j.clarke@wsu.edu |
| المصدر: |
Toxicology. Dec2021, Vol. 464, pN.PAG-N.PAG. 1p. |
| مصطلحات موضوعية: |
*NON-alcoholic fatty liver disease, *HEPATIC fibrosis, *GENE expression, *RATS, *SPRAGUE Dawley rats |
| مستخلص: |
• Recovery from MCLR toxicity did not resolve burnt-out NASH phenotype in NASH. • MCLR-elicited fibrosis persisted through 4 weeks of recovery in NASH. • MCLR persistently dysregulated cancer-related genes through 4 weeks of recovery in NASH. Nonalcoholic steatohepatitis (NASH) causes liver extracellular matrix (ECM) remodeling and is a risk factor for fibrosis and hepatocellular carcinoma (HCC). Microcystin-LR (MCLR) is a hepatotoxin produced by fresh-water cyanobacteria that causes a NASH-like phenotype, liver fibrosis, and is also a risk factor for HCC. The focus of the current study was to investigate and compare hepatic recovery after cessation of MCLR exposure in healthy versus NASH animals. Male Sprague-Dawley rats were fed either a control or a high fat/high cholesterol (HFHC) diet for eight weeks. Animals received either vehicle or 30 μg/kg MCLR (i.p: 2 weeks, alternate days). Animals were euthanized at one of three time points: at the completion of the MCLR exposure period and after 2 and 4 weeks of recovery. Histological staining suggested that after four weeks of recovery the MCLR-exposed HFHC group had less steatosis and more fibrosis compared to the vehicle-exposed HFHC group and MCLR-exposed control group. RNA-Seq analysis revealed dysregulation of ECM genes after MCLR exposure in both control and HFHC groups that persisted only in the HFHC groups during recovery. After 4 weeks of recovery, MCLR hepatotoxicity in pre-existing NASH persistently dysregulated genes related to cellular differentiation and HCC. These data demonstrate impaired hepatic recovery and persistent carcinogenic changes after MCLR toxicity in pre-existing NASH. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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