3-nitrotyrosine and Lead-Poisoning

Lead (Pb) is a heavy metal that plays an unknown biological role and is very toxic even at low concentrations. The main sources of Pb are Pb-contaminated areas in industrial areas or landfills. Inhalation is one of the most common routes of exposure to this metal, but there is little information on its effect on the liver. Thirty male mice were exposed to 0.1 M Pb acetate by inhalation for 8 weeks, twice a week for 1h. A recovery group was free of exposure for 4 weeks. Histological evaluation showed an increase in the inflammatory infiltrate and in the percentage of meganuclei in the liver. This was observed since the first week and throughout the whole exposure time. A significant increase in the aspartate aminotransferase concentration was observed in the liver function tests; yet, the alanine aminotransferase concentration did not show significant changes. The 4-hydroxynonenal (4-HNE) and nitrotyrosine levels in Pb-exposed mice, identified by immunohistochemistry, showed a significant increment compared to the controls. This effect was observed throughout Pb exposure. After a 4-week period of suspended exposure, recovery time, the concentration of 4-HNE and nitrotyrosine decreased to similar levels of those previously observed in controls, this suggests a decrease in the generation of oxidative stress by Pb inhalation. Although our results suggest that the lungs are the first contact organs and filters during Pb inhalation, this metal eventually reaches the liver and might cause damage by oxidative stress. This damage can decrease in time if exposure is discontinued.

Topics: Administration, Inhalation; Air Pollutants; Aldehydes; Animals; Atmosphere Exposure Chambers; Biomarkers; Hepatic Insufficiency; Immunohistochemistry; Lead; Lead Poisoning; Leukocytes, Mononuclear; Liver; Male; Mice; Neutrophil Infiltration; Nitrosative Stress; Oxidative Stress; Random Allocation; Tissue Distribution; Toxicity Tests, Acute; Toxicity Tests, Chronic; Toxicokinetics; Tyrosine

We have recently found evidence for increased reactive oxygen species (ROS) in rats with lead-induced hypertension. We hypothesized that increased ROS activity may contribute to hypertension by enhancing inactivation of nitric oxide (NO) in this model.. Rats were treated for 12 weeks with either lead acetate (100 p.p.m.) alone (Pb group) or lead acetate plus vitamin E-fortified food (5000 U/kg rat chow, Pb + E group). The control animals were fed either regular rat chow or a vitamin E-fortified diet. Blood pressure, creatinine clearance, and urinary excretion of stable NO metabolites (NOx) were monitored, and plasma and tissue abundance of nitrotyrosine, which is the footprint of NO oxidation by ROS, were determined.. The Pb group showed a marked rise in blood pressure, a significant increase in plasma and kidney, heart, liver, and brain nitrotyrosine abundance, and a substantial fall in urinary NOx excretion. Concomitant administration of high-dose vitamin E in the Pb + E group ameliorated hypertension and normalized both urinary NOx excretion and tissue nitrotyrosine without altering tissue lead content. However, vitamin E supplementation had no discernible effect on either blood pressure or nitrotyrosine abundance in the normal controls.. These findings point to enhanced ROS-mediated inactivation and sequestration of NO, which can potentially contribute to hypertension, tissue damage, and reduced urinary NOx excretion in rats with lead-induced hypertension. The beneficial effects of high-dose vitamin E on blood pressure, tissue nitrotyrosine burden, and urinary NOx excretion support the role of increased ROS activity in the pathogenesis of these abnormalities in this model.

Topics: Animals; Antioxidants; Blood Pressure; Blotting, Western; Brain Chemistry; Hypertension, Renal; Kidney; Lead; Lead Poisoning; Liver; Male; Myocardium; Nitric Oxide; Nitrogen Dioxide; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Tyrosine; Vitamin E