Pharmacokinetic model to describe the disposition of lead in the rat

Bornemann, L. D.; Colburn, Wayne A.

doi:10.1080/15287398509530769

Cited by 4 publications

(3 citation statements)

References 12 publications

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“…Long-term exposure to Pb leads to PKC activation in rat livers; however, Pb also inhibited the activity of PKCα in a human hepatoma cell line (Liu et al 1997; Tonner and Heiman 1997), and the inhibition was much more pronounced when Pb levels were high (Sun et al 1999). Because circulating Pb will quickly deposit in the liver (Bornemann and Colburn 1985), we speculated (Cheng and Liu 2005) that a transient accumulation of Pb in the liver will suppress the activation of PKC and p42/44 MAPK in hepatocytes. Pb or LPS alone at the doses we used did not alter the phosphorylation of p42/44 MAPK in HepG2 cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Lead Increases Lipopolysaccharide-Induced Liver Injury through Tumor Necrosis Factor-α Overexpression by Monocytes/Macrophages: Role of Protein Kinase C and p42/44 Mitogen-Activated Protein Kinase

Cheng

Yang

Liu

2006

Environ Health Perspect

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Although lead and lipopolysaccharide (LPS), both important environmental pollutants, activate cells through different receptors and participate in distinct upstream signaling pathways, Pb increases the amount of LPS-induced tumor necrosis factor-α (TNF-α). We examined the cells responsible for the excess production of Pb-increased LPS-induced TNF-α and liver injury, and the roles of protein kinase C (PKC) and p42/44 mitogen-activated protein kinase (MAPK) in the induction of TNF-α. Peritoneal injection of Pb alone (100 μmol/kg) or a low dose of LPS (5 mg/kg) did not affect serum TNF-α or liver functions in A/J mice. In contrast, coexposure to these noneffective doses of Pb plus LPS (Pb+LPS) strongly induced TNF-α expression and resulted in profound liver injury. Direct inhibition of TNF-α or functional inactivation of monocytes/macrophages significantly decreased the level of Pb+LPS-induced serum TNF-α and concurrently ameliorated liver injury. Pb+LPS coexposure stimulated the phosphorylation of p42/44 MAPK and the expression of TNF-α in CD14+ cells of cultured mouse whole blood, peritoneal macrophages, and RAW264.7 cells. Moreover, blocking PKC or MAPK effectively reduced Pb+LPS-induced TNF-α expression and liver injury. In summary, monocytes/macrophages were the cells primarily responsible for producing, through the PKC/MAPK pathway, the excess Pb-increased/LPS-induced TNF-α that caused liver injury.

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Section: Discussionmentioning

confidence: 99%

Lead Increases Lipopolysaccharide-Induced Liver Injury through Tumor Necrosis Factor-α Overexpression by Monocytes/Macrophages: Role of Protein Kinase C and p42/44 Mitogen-Activated Protein Kinase

Cheng

Yang

Liu

2006

Environ Health Perspect

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“…Although Pb causes anemia and hypertension, damage to the kidneys, the nervous, endocrine, and reproductive systems, and neurologic, neurobehavioral, and developmental effects in children, Pb does not directly damage the liver (9). Excess free Pb may be released from the liver to the blood after rats are treated with high doses of Pb (10). It has been postulated that chronic lead poisoning does not cause liver damage, but that a huge single dose of lead will cause hepatic damage (11).…”

Section: Introductionmentioning

confidence: 99%

Coexposure of Lead- And Lipopolysaccharide-Induced Liver Injury in Rats: Involvement of Nitric Oxide-Initiated Oxidative Stress and TNF-??

Liu

Cheng

Chen³

et al. 2005

Shock

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In this study, we investigated the interaction between lipopolysaccharide (LPS) and lead (Pb) and the involvement of tumor necrosis factor-alpha (TNF-alpha) and oxidative stress in Pb-plus-LPS (Pb/LPS)-induced liver damage in rats. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-alpha, nitric oxide (NO), and lipid peroxidation (LPO) were determined in rats treated with Pb and/or LPS. Pb ranging from 0 to 15 mg/kg dose dependently increased AST, ALT, NO, or LPO in LPS-treated rats. Pretreatment with iNOS inhibitor 1400W reduced NO, LPO, TNF-alpha, AST, and ALT in Pb/LPS-treated rats. Thus, Pb increased LPS-induced liver damage, which might be associated with increased NO-initiated oxidative stress and TNF-alpha in rats.

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“…Cadmium is responsible for disorders like anemia, aborted fetus, neonatal death, heart problem (Kjellstrom, 1985) renal tubular dysfunction, disturbances of the calcium homeostasis (Staessen et al, 1992). Lead interferes with the activity of enzymes and effects many organs and systems such as kidneys and central nervous system (Bornemann and Colburn, 1985). The present study was conducted to isolate, characterize the air borne bacteria of the polluted environments and to study the relation ship of pollutants and bacterial genetic characters.…”

Section: Introductionmentioning

confidence: 99%

Inducible Tolerance to Heavy Metals in Air Borne Bacteria

Ahmed¹,

Fasim²,

Arif³

et al. 2000

Pakistan J. of Biological Sciences

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Airborne bacteria were isolated from three polluted sites around Karachi. Among 30 isolates CMG 921 (Proteus mirabllis), 922 (Pseudomonas putida), 923 (Pseudornonas pseudomallei) and 924 (Yersinia aldovae) were selected and studied. All these strains belonged to Gaddani and were resistant to multiple metals indicating the high level of pollution in Gaddani. These strains were sensitive to most of the antibiotics except ampicillin. It was found that the metal resistant did not involve the outer membrane permeability however the resistance to copper and nickel was inducible. A single band of plasmid DNA of 2 kb was observed in CMG 921 and CMG 922 which have shown the same level of metal resistance. This has suggested that there is a horizontal transfer of plasmid pAN10 from one strain to another and perhaps the metal resistant determinants present on this plasmid.

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Pharmacokinetic model to describe the disposition of lead in the rat

Cited by 4 publications

References 12 publications

Lead Increases Lipopolysaccharide-Induced Liver Injury through Tumor Necrosis Factor-α Overexpression by Monocytes/Macrophages: Role of Protein Kinase C and p42/44 Mitogen-Activated Protein Kinase

Lead Increases Lipopolysaccharide-Induced Liver Injury through Tumor Necrosis Factor-α Overexpression by Monocytes/Macrophages: Role of Protein Kinase C and p42/44 Mitogen-Activated Protein Kinase

Coexposure of Lead- And Lipopolysaccharide-Induced Liver Injury in Rats: Involvement of Nitric Oxide-Initiated Oxidative Stress and TNF-??

Inducible Tolerance to Heavy Metals in Air Borne Bacteria

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