Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fumonisin B1 (FB1) is a naturally occurring mycotoxin produced by Fusarium verticillioides. Dietary exposure to FB1 has been linked to human cancer in certain parts of the world, and treatment with FB1 causes oval cell proliferation and liver tumors in rats. To study the potential role of oval (liver progenitor) cells in the cellular pathogenesis of FB1-induced liver tumors, we gave male F344 rats prolonged treatment with FB1 for 25 weeks, followed by return to control diet until 50 weeks ('stop study'). The time course of FB1-induced liver lesions was followed by examination of serial liver biopsies at set time intervals and post-mortem liver tissue at the end of the study. The effects of different FB1 treatment regimens (5 versus 25 weeks), as well as the modulating effect of 2-acetylaminofluorene (2-AAF), on the kinetics of oval cell proliferation and development of liver tumors were compared. Prolonged treatment with FB1 in normal diet caused persistent oval cell proliferation and generation of both hepatic adenomas and cholangiofibromas (CFs). These liver lesions occurred in the setting of chronic toxic hepatitis and liver fibrosis/cirrhosis, similar to that seen in human hepatocarcinogenesis. Some adenomas and CFs were dysplastic, and one post-mortem liver contained a hepatocellular carcinoma. OV-6+ oval cells were noted in close relation to proliferative neoplastic liver lesions, and some of these lesions expressed OV-6, suggesting that all these cell types were derived from a common progenitor cell. 2-AAF enhanced the size of FB1-induced glutathione S-transferase pi+ hepatocellular lesions and the incidence of CFs in post-mortem liver specimens, but this was not statistically significant. In conclusion, this study supports the involvement of dietary FB1 in liver carcinogenesis in male F344 rats. Oval cells may be the source of both the hepatocellular and cholangiocellular tumors induced by prolonged treatment with FB1. 2-AAF appears to have an enhancing effect on FB1-induced liver tumors, presumably due to its potent inhibitory effects on hepatocyte regeneration.
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PMID:Fumonisin B1-induced hepatocellular and cholangiocellular tumors in male Fischer 344 rats: potentiating effects of 2-acetylaminofluorene on oval cell proliferation and neoplastic development in a discontinued feeding study. 1498 22

Ethnopharmacological Relevance. "Diwu Yanggan" (DWYG) has been reported to regulate liver regeneration, modulate the immune response, ameliorate liver injury, kill virus, ameliorate liver fibrosis, and suppress hepatic cancer. However, its mechanisms are still unknown. Objectives. To investigate the effects of DWYG on oval cell proliferation in 2-AAF/PH rats and determine its mechanism. Methods. Wistar rats were randomly distributed into normal group, sham group, vehicle group, and DWYG group. Hepatic pathological changes were examined by H&E staining. The oval cell markers CD34, AFP, CK-19 and hematopoietic cell markers CD45, Thy1.1, and hepatocyte marker ALB were examined with immunohistochemistry. The percentage of CD34/CD45 double-positive cells in bone marrow was detected by flow cytometry. Cytokine levels were measured with the Bio-plex suspension array system. Results. DWYG significantly increased the survival rates of 2-AAF/PH rats and promoted liver regeneration. Furthermore, DWYG increased the ratio of CD34/CD45 double-positive cells on days 10 and 14. In addition, DWYG gradually restored IL-1, GRO/KC, and VEGF levels to those of the normal group. Conclusions. DWYG increases 2-AAF/PH rat survival rates, suppresses hepatic precarcinoma changes, and restores hepatic tissue structure and function. DWYG may act by modulating the hepatic microenvironment to support liver regeneration.
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PMID:The herbal compound "diwu yanggan" modulates liver regeneration by affecting the hepatic stem cell microenvironment in 2-acetylaminofluorene/partial hepatectomy rats. 2562 49