Magic™ Anti-4-HNE monoclobal antibody

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.

Traumatic brain injury (TBI) leads to a deleterious and multifactorial secondary inflammatory response in the brain. Oxidative stress from the inflammation likely contributes to the brain damage although it is unclear to which extent. A largely unexplored approach is to consider phenotypic regulation of oxidative stress levels. Genetic polymorphism influences inflammation in the central nervous system and it is possible that the antioxidative response differs between phenotypes and affects the severity of the secondary injury. We therefore compared the antioxidative response in inbred rat strains dark agouti (DA) to piebald viral glaxo (PVG). DA has high susceptibility to inflammatory challenges and PVG is protected. Primary neuronal cell cultures were exposed to peroxynitrite (ONOO-), nitric oxide (NO), superoxide (O-2(-)), and 4-hydroxynonenal (4-HNE). Our findings demonstrated a phenotypic control of the neuronal antioxidative response, specific to manganese O-2(-) dismutase (MnSOD). DA neurons had increased levels of MnSOD, equal levels of peroxiredoxin 5 (PRDX5), decreased oxidative stress markers 3-nitrotyrosine (3-NT) and 4-HNE and decreased neuronal death detected by lactate dehydrogenase (LDH) release after 24 h, and higher oxidative stress levels by CellROX than PVG after 2 h. It is possible that DA neurons had a phenotypic adaptation to a fiercer inflammatory environment. ONOO- was confirmed as the most powerful oxidative damage mediator, while 4-HNE caused few oxidative effects. Inducible NO synthase (iNOS) was not induced, suggesting that inflammatory, while not oxidative stimulation was required. These findings indicate that phenotypic antioxidative regulation affects the secondary inflammation, which should be considered in future individualized treatments and when evaluating antioxidative pharmacological interventions.