Background and aim: Hepatocellular carcinoma (HCC) is a primary neoplasm of the liver with high recurrence and high mortality rate. The etiological factors are hepatitis B and/or C virus infections, non-alcoholic steatohepatitis, alcohol consumption, and aflatoxin b1 exposition. These factors promote inflammation, fibrosis, and cirrhosis, and alter the expression of genes and molecular mechanisms, initiating hepatocarcinogenesis. The modified resistant hepatocyte model (MRHM) has been established which simulates the stages of carcinogenesis. Pirfenidone (PFD) has shown antifibrotic, anti-inflammatory and antioxidant effects in liver damage models, so the aim was to evaluate the administration of PFD on histopathological alterations and the expression of key proteins in the development of hepatocarcinogenesis in MHRM.
Material and methods: Longitudinal experimental study. 30 Wistar rats were divided into 3 groups: control group, carcinogenic damage group, and carcinogenic damage group plus daily administration of PFD. The physical and clinical data of the animals were analyzed at 30 days. All tissues were subjected to H&E, and Masson trichrome histological assays, and analysis of proteins involved in liver fibrosis, acute and chronic inflammation, apoptosis, cell division, tumor promotion/suppression, and cell metabolism using Western-Blot tests and microscopy confocal. Experiments for triplicate were performed; data were analyzed and plotted in GraphPad Prism 7.
Results: Morphological analysis: damage group shows dense, pale brown and inflamed livers compared to control and PFD groups. PFD administration prevents damage in the hepatocyte architecture, reduces periportal fibrosis and prevents inflammation overexpression markers (NFkB, IL-6, and TNFalpha) and cell division activation. PFD increases apoptotic markers expression (Cas-3), tumor suppressors (p53) and re-establishes proteins in cellular metabolism regulation (PPARalpha/PPARgamma).
Conclusions: PFD administration prevents chemical-induced carcinogenic damage in MMRH. PFD decreases fibrotic and proinflammatory markers; likewise, PFD regulates tumor suppressor and mitogenic markers.
This research has been partially subsidized by CONACyT 259096 CB-2015-01 basic science and CONACyT scholarship No. 461588.
Conflicts of interest: The authors have no conflicts of interest to declare.