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Oral cocaine administration results in hepatic necrosis, increased plasma transaminase concentration, and decreased antioxidative capability, which is potentiated by lipopolysaccharide (LPS) in male CF-1 mice. Females administered the same treatment regimen display none of the hepatotoxic effects seen in their male counterparts. This study was conducted to further dissect the mechanism responsible for this gender difference in cocaine hepatotoxicity (CH) and lipopolysaccharide potentiation of CH. Male and female CF-1 mice were orally administered 20 mg/kg cocaine hydrochloride once daily for 7 days. Four hours after the last cocaine administration the mice were administered 12 × 10 6 EU LPS intraperitoneally. The activity of plasma esterase (butyrylcholinesterase), the enzyme responsible for the major pathway of cocaine metabolism to nonhepatotoxic metabolites, was measured. Aminotransferase release and histological analysis were used to determine hepatotoxicity. The concentration of the hepatotoxic precursor norcocaine was measured in the plasma and liver. Regardless of treatment, males were shown to have only 30% of the plasma esterase activity displayed by females. In addition, administration of testosterone to ovariectomized females resulted in a 70% reduction in plasma esterase activity when compared with surgically unaltered females. Moreover, hepatic norcocaine was not detected in the plasma or liver of surgically unaltered female animals, while it was present in males and testosterone-supplemented ovariectomized females. These results indicate that plasma esterase activity is heavily influenced by sex hormones, predominantly testosterone, in CF-1 mice. Suppression of plasma esterase by testosterone correlates with decreased norcocaine production and is therefore responsible, in part, for the increased CH seen following oral administration with and without LPS exposure in male CF-1 mice. [ABSTRACT FROM AUTHOR]

Cocaine produces hepatotoxicity by a mechanism that remains undefined but that has been linked to its oxidative metabolism. Endotoxin (lipopolysaccharide, LPS) is also a well-known cause of hepatic damage, where exposure to non-injurious doses of LPS increases the toxicity of certain hepatotoxins. This study was conducted to investigate the possible potentiation of cocaine-mediated hepatotoxicity (CMH) by LPS. Male CF-1 mice were administered oral cocaine hydrochloride for 5 consecutive days at a dose of 20 mg/kg with and without 12 × 10[sup 6] EU LPS/kg given intraperitoneally 4 h after the last cocaine injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured as markers of liver injury. Blood and liver glutathione (GSH) levels were determined, as well as the activities of glutathione peroxidase (GPx) and catalase (CAT). In addition, the activity of liver glutathione reductase (GRx) was measured. The results demonstrate that endotoxin potentiated the hepatotoxicity of cocaine. Serum ALT and AST were significantly elevated with the combined cocaine and LPS treatment versus all other treatments. While cocaine alone resulted in centrilobular necrosis, the cocaine and LPS combination produced submassive necrosis. The increased hepatic GSH content and GRx activity observed with cocaine alone were not observed with the combination treatment, rendering the liver more susceptible to oxidative stress. Moreover, there was a significant decrease in the activities of hepatic GPx and CAT, particularly with the combination treatment. In conclusion, this study demonstrates that LPS potentiates the hepatotoxicity of cocaine as revealed by an array of biochemical and morphological markers. [ABSTRACT FROM AUTHOR]

Presents information on a study which determined the dermal bioavailability of soil-aged benzopyrene (BaP). Details of polycyclic aromatic hydrocarbons; Total skin penetration of BaP; Effect of chemical aging and surface adsorption on reducing the bioavailability of BaP in soil.

The dermal bioavailability of mercury ''aged'' in soil for 3 mo was compared to that of pure mercury (without soil) and to mercury in brief contact with soil (16 h). Studies were conducted in vitro with [203Hg]mercuric chloride on dermatomed male pig skin by flow-through diffusion cell methodology. Less than 0.5% of the initial mercury dose penetrated through skin into receptor fluid after each treatment. The majority of pure mercury became covalently bound to skin. However, a short contact time with either an Atsion (sandy) or Keyport (clay) soil significantly decreased the total penetration of mercury (sum of receptor fluid and skin) by 40%. After aging, a 95% reduction in total penetration was observed for the compound relative to chemical without soil. Both soils bind mercury more strongly with time, as evidenced by larger quantities of radioactivity in soil and smaller amounts in skin decontaminate after aging than in soil for 16 h. Decreased mercury bioavailability with aging indicates lower health risk and reduced need for soil cleanup. [ABSTRACT FROM AUTHOR]

It has been shown that gold accumulates in macrophages. In vitro studies have also shown that long-term anti-inflammatory and immuno-regulatory effects on these cells may be responsible for the effectiveness of gold in the treatment of rheumatoid arthritis. However, the relevance of this information to the in vivo circumstance is largely untested. In this study, the effect of gold sodium thiomalate (AuTM) on rat alveolar macrophage (AM) lysosomal enzymes, bacterial killing, and metabolic activities associated with phagocytosis were assessed after in vivo administration. The activities of β-glucuronidase, acid phosphatase, and lysozyme were inhibited 1 day following a single AuTM injection (50 mg/kg, subcutaneous). However, lysozyme returned to normal, while the activities of β-glucuronidase and acid phosphatase were elevated from 4 to 12 days thereafter. When AuTM was administered weekly for 8 weeks, the activities of acid phosphatase and β-glucuronidase were elevated throughout, while lysozyme was largely unaffected. The increased lysosomal enzyme activities were not due to contamination of polymorphonuclear leukocytes. These long-term effects of AuTM on enzyme activity were in marked contrast to its in vitro effect which inhibited the activities of β-glucuronidase and acid phosphatase. No effect of AuTM administration on the release of β-glucuronidase upon phagocytosis of opsonized zymosan was observed. At 1 day following a single AuTM injection or 3 days after a second weekly injection, in vivo bactericidal activity of AM toward S. aureus was diminished. This bacterial killing defect was not due to decreased phagocytosis; the in vivo binding and ingestion of bacteria were normal. The defect correlated with impaired metabolic activities associated with phagocytosis, namely a significant decrease in the reduction of nitroblue tetrazolium and the stimulation of the hexose monophosphate shunt. This may be an attractive anti-inflammatory effect in light of the destructive potential of the reactive oxygen species produced by macrophages in an arthritic circumstance. [ABSTRACT FROM AUTHOR]