Gallic acid modifies EGFR phosphorylation in rat with hepatic preneoplasia

Abstract

<b>Abstract ID 17052</b> <b>Poster Board 263</b> Our aim was to study the effect of gallic acid on EGFR phosphorylation on liver rats with preneoplastic lesion induced by administration of diethylnitrosamine (DEN) and carbon tetrachloride (CCl₄). For this study, we used male Wistar rats which were randomly divided into four groups: (1) Control (50 mL) of water;(2) Gallic acid (50 mg/kg) per v.o. dayly for 8 weeks; (3) Preneoplastic liver lesion induced by administration of unique dose of Diethylnitrosamine i.p. (200 mg/kg body weight) and then treated two weeks later with a single dose of CCl₄(4 mL/kg) diluted in mineral oil (1:1), i.p. during 8 weeks; and (4) Rats receiving both carcinogens and gallic acid simultaneously as described above. Rats were sacrificed and liver tissue was collected for analyzing EGFR expression and tyrosine phosphorylation pY1068. For identification of total EGFR and pY1068 EGFR, a western blotand immunohistochemical analysis were carried out. We performed histological examination of liver tissue using H&amp;E staining as well as an immunohistochemical analysis for PCNA. All procedures were approved by the Institutional Animal Care and Use Committee of the Veterinary Medical School at the National Autonomous University of Mexico. The experiments were conducted in accordance with the principles set forth in the Care and Use of Laboratory Animals Guide. Our study revealed, scattering preneoplastic lesions through liver parenchyma, such as focal coagulative necrotic changes, presence of bi-nucleated nucleus and focal fatty changes in animals receiving carcinogens. Total EGFR and tyrosine phosphorylation at pY1068 EGFR were significantly increased in animals developing preneoplastic lesions (2.5-fold and 10-fold, respectively) as compared to control group (p &lt;0.05). Those findings were associated with a significant increase in PCNA expression (12-fold) (p&lt;0.05). Interestingly, our result showed that gallic acid reduced EGFR expression and phosphorylation at pY1068 EGFR in animals developing preneoplastic lesions. A significant reduction in total EGFR (2.5-fold) and tyrosine phosphorylation at pY1068 EGFR (7.5-fold) were found as compared with preneoplasia group (p&lt;0.05). The reduction in EGFR expression and phosphorylation was associated with a reduction in PCNA expression. A reduction of preneoplastic lesions and an improvement in liver tissue was also observed. In conclusion, gallic acid might influence in EGFR cell signaling pathway in the liver during developing of preneoplastic lesion, reducing cell proliferation and improving liver architecture. Further studies are needed to evaluate the potential usefulness of gallic acid as a promising hepatoprotective agent.