Immunoelectron microscopy identification of early proliferating cells in rat liver tissue during hyperplasia induced by lead nitrate

Abstract

Recent studies have suggested that hepatic stem cells may be involved in at least some forms of liver epithelial growth. To obtain further information on this controversial hypothesis, we treated rats with lead nitrate to induce liver growth and identified the cells undergoing early DNA synthesis by bromodeoxyuridine immunohistochemistry, using both light and electron microscopic detection methods. Eight hours after an intravenous injection of lead nitrate 100 mumol/kg, DNA synthesis was detected in a few scattered hepatocytes and in nonparenchymal cells in portal connective tissue. At the light microscopic level, identification of nonparenchymal cells was limited to bile duct epithelial cells. Other cell types were also labeled, but their identity could not be established. At the ultrastructural level, however, four types of nonparenchymal cells were identified as containing bromodeoxyuridine immunogold particles. These four types included bile duct epithelial cells, fibroblasts, macrophages and nondescript periductular cells. These periductular cells displayed certain ultrastructural features of bile duct cells but did not line a lumen or display microvilli on their apical membrane, nor did they reside within the bile duct basement membrane. Because proliferation of nonparenchymal cells in portal areas preceded that of hepatocytes, it is suggested that the former reaction reflects a direct mitogenic effect of lead nitrate and not an adaptive growth response secondary to parenchymal enlargement. However, whether DNA synthesis in periductular cells or bile duct cells reflects activation of hepatic stem cells cannot be established from the present morphological observations. If so, such a progenitor compartment must be dormant because it does not seem to play a functional role in this and other forms of adult liver epithelial growth.

Bioactive peptide carnosin protects against lead acetate-induced hepatotoxicity by abrogation of oxidative stress in rats

“…Generally, these results indicate degenerative changes and hypofunction of liver, which confirm the earlier observations (Nehru & Kaushal 1993;Singh et al 1994;El-Nekeety et al 2009). Damage to hepatic structural integrity induced by lead acetate is further supported by our histopathological study, where the liver tissue of the animals treated with lead revealed severe destruction of hepatic architecture, necrosis, infiltration of inflammatory cells typical to those reported in the literature (Rijhsinghani et al 1993;Kubo et al 1996). Evidence of oxidative stress has been detected in liver injury following lead exposure.…”

Liver Cell Proliferation Induced by Nafenopin and Cyproterone Acetate Is Not Associated With Increases in Activation of Transcription Factors Nf–κB and Ap–1 or With Expression of Tumor Necrosis Factor α

“…11, 45 Kupffer cells are the main producers of TNFFurthermore, our present data suggest that direct hyperplasia may be induced two different ways: via TNF-a, such a, a strong inducer of NF-kB, and Kupffer cell/hepatocyte cocultures release NO upon immunological activation by as in the case of LN, or through binding of the mitogens to nuclear receptors of the superfamily of the steroid hormones LPS. 46 Moreover, Kupffer cell products are required for NO production in hepatocytes.…”

Effects of isoquinoline alkaloid berberine on lipid peroxidation, antioxidant defense system, and liver damage induced by lead acetate in rats

“…Similar observations have been reported previously. 30,31 Accumulating evidence shows that liver injury following lead exposure is associated with oxidative damage. Lead is not able to induce production of free radicals directly, but it indirectly influences the processes of lipid peroxidation, leading to loss of membrane integrity and tissue damage.…”