Hepatic expression of heme oxygenase-1 and antioxidant response element-mediated genes following administration of ethinyl estradiol to rats.

Heme oxygenase-1 (HO-1) is one of several enzymes induced by hepatotoxicants, and is thought to have an important protective role against cellular stress during liver inflammation and injury. The objective of the present study was to evaluate the role of HO-1 in estradiol-induced liver injury. A single dose of ethinyl estradiol (500 mg/kg, po) resulted in mild liver injury.

Peroxides and macrophages in the toxicity of fine particulate matter in rats.

Epidemiologists have observed a positive association between human morbidity and mortality and the atmospheric concentrations of fine particulate matter (PM), but the mechanisms underlying the toxic effects of PM have not been elucidated. Various components of ambient PM have been implicated in toxicity (including ultrafine particles, transition metals, organics and oxidants). Our research focused on hydrogen peroxide (H2O2).

Tissue injury following inhalation of fine particulate matter and hydrogen peroxide is associated with altered production of inflammatory mediators and antioxidants by alveolar macrophages.

Hydrogen peroxide (H(2)O(2)) is present in the atmosphere at concentrations known to induce cell and tissue damage. However, inhaled H(2)O(2) vapor should not reach the lower lung due to its high water solubility. It has been suggested that hygroscopic components of particulate matter (PM) may transport H(2)O(2) into the lower lung and induce tissue injury and this was investigated.

Distinct roles of tumor necrosis factor-alpha and nitric oxide in acute liver injury induced by carbon tetrachloride in mice.

Macrophages are known to release a number of different inflammatory mediators with cytotoxic potential. In the present studies we analyzed the role of two macrophage-derived mediators, tumor necrosis factor-alpha (TNF-alpha) and nitric oxide, in liver injury induced by carbon tetrachloride (CCl4). Treatment of mice with CCl4 resulted in a dose- and time-dependent induction of centrilobular hepatic necrosis.

Functional heterogeneity of rat hepatic and alveolar macrophages: effects of chronic ethanol administration.

Chronic ethanol consumption is associated with increased incidence of hepatic and pulmonary infections. To determine if this is correlated with altered macrophage activity, we analyzed the functional properties of cells isolated sequentially from the liver and lung of rats fed a liquid diet containing ethanol (35% of calories) or malto-dextrin control for 9-12 weeks. Hepatic and alveolar macrophages from control animals were found to exhibit distinct morphologic and functional properties.