Hepatocyte Ploidy in Regenerating Livers after Partial Hepatectomy, Drug-Induced Necrosis, and Cirrhosis

Abstract

The hepatocyte ploidy was investigated by flow cytometry in regenerating Sprague-Dawley rat livers following either drug-induced acute necrosis (single sublethal doses of D-galactosamine or thioacetamide) or drug-induced chronic cirrhosis (repeated thioacetamide injections for 10–18 weeks) and in regenerating livers following 70% partial hepatectomy and was compared with that of normal hepatocytes. Twenty-four hours after partial hepatectomy, a significant decrease in 2n (1 diploid nucleus) hepatocytes and a significant increase in 8n (1 octoploid nucleus) hepatocytes occurred. In contrast, 24 h following induction of acute hepatic failure by single D-galactosamine or thioacetamide injections, a significant increase in 2n hepatocytes was observed, whereas the proportion of 8n hepatocytes remained unchanged. The liver ploidy returned to basal values within 21 days in all cases. In cirrhotic livers induced by chronic thioacetamide injections, the rate of 2n hepatocytes was about ten times that of the controls having the same age, while 4n (1 tetraploid nucleus) and 8n hepatocytes were one third of controls. The binucleation rate was also significantly decreased.

Effect of angiotensin-converting enzyme inhibitor, lisinopril on morphological and biochemical aspects of fibrotic liver regeneration

“…Increased hepatocyte ploidy during liver regeneration following PHx has already been reported. [26] ACE inhibitor captopril was found to decrease the hepatocyte cellular size at 48 h after PHx during normal liver regeneration[11] whereas in this study we observed that lisinopril treatment did not affect hepatocyte nuclear or cellular area, leading to conclude that it had no effect on hepatocyte hypertrophy during fibrotic liver regeneration.…”

Mechanism of plasmid delivery by hydrodynamic tail vein injection. II. Morphological studies

“…In normal, non‐injected livers hepatocytes were arranged in hepatic plates, mostly with radian position in respect to hepatic veins or portal triads (Figure 1A). All zones of the hepatic unit showed heterogeneity in hepatocyte size, as well as minimal variations in cytoplasm density and vacuolization (Figure 1B—zone 3, Figure 1C—zone 1), which is typical for rodent liver 25, 26.…”

Tetraploidy/aneuploidy and stem cells in cancer promotion: The role of chromosome passenger proteins

“…Numerous studies have shown that normal diploid cells of other lineages can be induced to undergo polyploidization via endomitosis as a consequence of stress (e.g., hypertension and senescence (reviewed in Ravid et al (2002))). In addition, polyploid hepatocytes have been described to increase in number dramatically upon oxidative stress or after partial hepatoectomy (Dethloff and de la Iglesia, 1998; Gupta, 2000; Gandillet et al, 2003). Endothelial cells and fibroblasts have been shown in tissue biopsies and in cell culture to become polyploid upon aging and during tissue repair (Oberringer et al, 1999; Wagner et al, 2001).…”