The epidermal growth factor receptor (EGFR) plays an important role on hepatic protection in acute and chronic liver injury. The aim of this study was to investigate the role of genistein on EGFR expression, phosphorylation and signaling pathways in experimental subacute liver damage induced by carbon tetrachloride (CCl₄). We used male Wistar rats that were randomly divided into four groups: (1) Control; (2) Genistein 5 mg/kg per oral; (3) Subacute liver damage induced by CCl₄ 4 mg/kg subcutaneously; and (4) Animals received CCl₄ and genistein at the dosage indicated. The effect of genistein on EGFR expression, phosphorylation and signaling pathways were investigated by western blot and densitometric analyses. Histological changes were evaluated on slices stained with Hematoxylin-Eosin and Masson´s trichromic, as well as an immunohistochemical analysis for proliferating cell nuclear antigen (PCNA). Additionally, pro-inflammatory cytokines and liver enzymes were quantified. Our study showed that genistein increased EGFR expression, EGFR-specific tyrosine residues phosphorylation (pY1068-EGFR and pY84-EGFR), signal transducer and activator of transcription phosphorylation (pSTAT5), protein kinase B phosphorylation (pAKT) and PCNA in animals with CCl₄-induced subacute liver damage. It was found a significant reduction of pro-inflammatory cytokines in serum from animals with subacute liver damage treated with genistein. Those effects were reflected in an improvement in the architecture and liver function. In conclusion, genistein can induce a transactivation of EGFR leading to downstream cell signaling pathways as early events associated with regeneration and hepatoprotection following subacute liver damage.

表皮生长因子受体（EGFR）在急慢性肝损伤中发挥重要的肝脏保护作用。本研究的目的是探讨金雀异黄素对四氯化碳（CCl 4 _）诱导的实验性亚急性肝损伤中EGFR表达、磷酸化和信号通路的作用。我们使用雄性 Wistar 大鼠，将其随机分为四组：（1）对照组；(2)金雀异黄酮每次口服5mg/kg；_{(3)CCl 4} 4mg/kg皮下注射致亚急性肝损伤；(4) 接受 CCl _{4 的动物}和染料木黄酮按指定剂量。通过蛋白质印迹和光密度分析研究金雀异黄酮对 EGFR 表达、磷酸化和信号通路的影响。对苏木精-伊红和马森三色染色的切片进行组织学变化评估，并对增殖细胞核抗原（PCNA）进行免疫组织化学分析。此外，还对促炎细胞因子和肝酶进行了定量。我们的研究表明，金雀异黄素可增加 CCl 4 动物中的 EGFR 表达、EGFR 特异性酪氨酸残基磷酸化（pY1068-EGFR 和 pY84-EGFR）、信号转导子和转录磷酸化激活剂（pSTAT5）、蛋白激酶 B 磷酸化（pAKT）和_PCNA引起的亚急性肝损伤。研究发现，接受金雀异黄素治疗的亚急性肝损伤动物血清中促炎细胞因子显着减少。这些效果反映在结构和肝功能的改善上。总之，金雀异黄素可以诱导 EGFR 反式激活，从而导致下游细胞信号传导途径，作为与亚急性肝损伤后再生和肝保护相关的早期事件。