Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats

TLDR

The study aimed to assess oval cell activation and AFP expression when 2‑AAF is combined with selective centrilobular (CCl₄) or periportal (AA) liver injury. The authors induced centrilobular or periportal damage using CCl₄ or AA after 2‑AAF treatment and measured oval cell proliferation and AFP mRNA levels. Combining 2‑AAF with centrilobular injury produced the strongest oval cell proliferation and AFP expression, exceeding that seen with periportal injury or 2‑AAF alone, while acute AA or CCl₄ alone elicited minimal AFP expression, indicating that hepatocyte proliferation inhibition and periportal matrix components are key to oval cell activation.

Abstract

Administration of 2-acetylaminofluorene (2-AAF) given before partial hepatectomy (PHx) results in suppression of hepatocyte proliferation and stimulation of oval cell proliferation. Our objective in this study was to examine the oval cell response and associated α-fetoprotein (AFP) gene expression by combining 2-AAF with selective damage of centrilobular regions (carbon tetrachloride [CCl 4 ]) or periportal regions (allyl alcohol [AA]). Centrilobular damage results in a more enhanced oval cell response and AFP gene expression than periportal damage. Conversely, more intense proliferation of intraportal bile duct epithelia was seen with 2-AAF/AA than with 2-AAF/CCl 4 . The oval cell response and AFP gene expression was ranked as 2-AAF/CCl 4 ≥ 2-AAF/PHx > 2-AAF/AA. AFP mRNA expression was also examined in an acute AA and CCl 4 injury. We found very little AFP gene expression compared with the 2-AAF/hepatic injury models. To see a true oval cell response, the hepatocytes must be inhibited from proliferating. In addition, the results presented with the 2-AA/AA model suggest that the periportal matrix may be as important as the cells that populate the area.