Cell proliferation, apoptosis, NF-κB expression, enzyme, protein, and weight changes in livers of burned rats

Abstract

Thermal injury has been shown to alter gut epithelium and heart myocyte homeostasis by inducing programmed cell death. The effect of thermal injury on hepatocyte apoptosis and proliferation, however, has not been established. The purpose of this study was to determine whether a large thermal injury increases liver cell apoptosis and proliferation and whether these changes were associated with alterations in hepatic nuclear factor kappaB (NF-kappaB) expression and changes in liver enzymes and amount of protein. Sprague-Dawley rats received a 40% total body surface area scald burn or sham burn. Rats were killed and livers were harvested at 1, 2, 5, and 7 days after burn. Liver cell apoptosis was determined by terminal deoxyuridine nick end labeling (TUNEL) assay and cell proliferation by immunohistochemistry for proliferating cell nuclear antigen. Hepatic NF-kappaB expression was determined by Western blot, and total hepatic protein content was determined by protein assay. Protein concentration decreased after burn compared with sham controls (P < 0.05). Liver cell apoptosis, proliferation, and NF-kappaB expression in hepatocytes increased in burned rats compared with controls (P < 0.05). It was concluded that thermal injury induces hepatic cell apoptosis and proliferation associated with an increase in hepatic NF-kappaB expression and a decrease in hepatic protein concentration.

The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

“…Immediately after burn, the damage of the liver may be associated with an increased hepatic edema formation. We (15) have shown that the liver weight and liver/ bodyweight significantly increased 2 to 7 days after burn when compared with controls. As hepatic protein concentration was significantly decreased in burned rats, we suggest that the liver weight gain is due to increased edema formation rather than increases in the number of hepatocytes or protein levels.…”

“…Liver damage has been associated with increased hepatocyte cell death (15). In general, cell death occurs by two distinctly different mechanisms: programmed cell death (apoptosis) or necrosis (30).…”

“…Advances in these areas improved postburn outcomes, but severe burn is still associated with significant morbidity and mortality. Our group (14)(15)(16)(17) proposed that an integral part of the postburn response has not been determined; therefore, we focused our research on the role of the liver. The liver, with its metabolic, inflammatory, immune, and acute phase functions, plays a pivotal role in patient survival and recovery by modulating multiple pathways (13).…”

Melatonin Protection against Burn-Induced Hepatic Injury by Down-Regulation and Nuclear Factor Kappa B Activation

“…Nuclear factor kappa B (NF-kB) is a transcriptional factor that plays a key role in inflammation and tissue damage, in the regulation of cell proliferation and apoptosis in human hepatic cells (8). It regulates the expression of multiple inflammatory genes, stressinduced responses, and survival (9).…”

Melatonin protects against burn-induced hepatic oxidative injury by inducing HO-1 via the Nrf2 pathway

“…The liver plays an important role in metabolism, inflammation, homeostasis and host defence mechanisms (Klein et al 2004), and is a major organ responsible for initiating multiorgan dysfunction syndrome (MODS) following burn injury. The mechanism of burn-induced injury is not completely understood; however, several mechanisms, including hypoxia, free radicals, inflammation, and apoptosis are thought to be involved (Jeschke et al 2001). The excessive production of free radicals such as superoxide anion, hydrogen peroxide and hydroxyl radicals as well as the occurrence of lipid peroxidation products such as malondialdehyde (MDA) due to oxidative stress are associated with burn-induced liver dysfunction (Horton 2003;Bekyarova et al 2009;Bekyarova et al 2012).…”