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.…”

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.…”

Cellular polyploidy in organ homeostasis and regeneration

“…Polyploid hepatocytes isolated within 5 days of partial hepatectomy are less proliferative than diploid hepatocytes ( Gorla et al, 2001 ), suggesting that partial hepatectomy-induced polyploid hampers cell proliferation. The notion that diploid cells proliferate faster than polyploid hepatocytes is also supported by several studies which observed that diploid hepatocytes are enriched in patients and rats with various disease states ( Anti et al, 1994 ; Rua et al, 1996 ; Gandillet et al, 2003 ).…”

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.…”

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.…”

Cellular polyploidy in organ homeostasis and regeneration

“…Polyploid hepatocytes isolated within 5 days of partial hepatectomy are less proliferative than diploid hepatocytes ( Gorla et al, 2001 ), suggesting that partial hepatectomy-induced polyploid hampers cell proliferation. The notion that diploid cells proliferate faster than polyploid hepatocytes is also supported by several studies which observed that diploid hepatocytes are enriched in patients and rats with various disease states ( Anti et al, 1994 ; Rua et al, 1996 ; Gandillet et al, 2003 ).…”

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.…”

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.…”

Cellular polyploidy in organ homeostasis and regeneration

“…Polyploid hepatocytes isolated within 5 days of partial hepatectomy are less proliferative than diploid hepatocytes ( Gorla et al, 2001 ), suggesting that partial hepatectomy-induced polyploid hampers cell proliferation. The notion that diploid cells proliferate faster than polyploid hepatocytes is also supported by several studies which observed that diploid hepatocytes are enriched in patients and rats with various disease states ( Anti et al, 1994 ; Rua et al, 1996 ; Gandillet et al, 2003 ).…”

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.…”