Reticuloendothelial and hepatic functional alterations following lead acetate administration

Trejo, Rafael A.; Luzio, N. R. Di; Loose, Leland D.; Hoffman, E.

doi:10.1016/0014-4800(72)90064-0

Cited by 64 publications

(15 citation statements)

References 20 publications

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“…Hepatic injury has been thought to be the cause of the observed increase in serum levels of serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, aldolase, as well as other cytoplasmic and mitochondrial enzymes (8,21,31).…”

Section: Discussionmentioning

confidence: 99%

“…Lead administration to animals causes changes in the liver (12,14) visible by light and electron microscopy. Additionally, it increases the concentrations of enzymes in serum released from damaged hepatocytes, and produces alterations in hepatocyte function as manifested by decreased bilirubin clearance and enhanced bromosulfophthalein retention (8,31). Recently, inhibition of the microsoma1 hepatic cytochrome P-450 dependent mixed function oxidase system has been reported (3,26) in lead intoxicated animals and humans, suggesting the possibility of an alteration in hepatic drug metabolism.…”

Section: Speculationmentioning

confidence: 99%

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Effect of Lead Exposure on the Activity of Some Hepatic Enzymes in the Rat

et al. 1979

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SummarySeven-day-old rats were fed 1% lead acetate tetrahydrate solution for 2,4, or 7 days. Adult rats were fed the same lead solution for 6-8 wk. In the newborn rats, hepatic UDP-bilirubin glucuronyl transferase (GT) and gamma glutamyl transpeptidase (GGTP) activities were markedly increased. GT activity was increased after 4 days as compared to the controls (6.3 f 0.3 vs. 4.3 f 0.3, P < 0.001), and was maximal after 7 days of treatment (7.5 f 0.4 vs. 4.6 f 0.4, P < 0.001). GGTP activity was already maximally increased after 2 days of lead treatment (1.4 rt: 0.2 vs. 0.4 f 0.1, P < 0.001). Hepatic GT and GGTP activities were similarly increased in adult rats (7.9 f 0.3 vs. 5.1 f 0.1, P < 0.001, and 0.7 f 0.1 vs. 0.4 f 0.1, P < 0.005, respectively). In vitro studies adding lead citrate to liver homogenates did not produce any direct effect on GT and GGTP activities. SpeculationThe increase in hepatic GT and GGTP activities in lead treated animals appears to be a response to lead induced cellular damage or may result from interference with regulatory mechanisms responsible for production of these enzymes and not related to hepatic enzyme induction. The hepatic metabolism of drugs ingested by children with an increased lead burden may, therefore, be significantly altered.While lead remains one of the more important industrial and environmental toxins, and a series of recent factors have reduced the incidence of lead exposure and toxicity (1 I), its affect on the liver has received relatively little attention when compared to its impact on hematopoietic and neuromuscular systems. Lead administration to animals causes changes in the liver (12, 14) visible by light and electron microscopy. Additionally, it increases the concentrations of enzymes in serum released from damaged hepatocytes, and produces alterations in hepatocyte function as manifested by decreased bilirubin clearance and enhanced bromosulfophthalein retention (8,31). Recently, inhibition of the microsoma1 hepatic cytochrome P-450 dependent mixed function oxidase system has been reported (3, 26) in lead intoxicated animals and humans, suggesting the possibility of an alteration in hepatic drug metabolism. In order to explore further the effects of lead on hepatic enzyme activity, microsomal, noncytochrome P-450 dependent systems were studied in rats previously shown to be poisoned by lead (17). MATERIALS A N D METHODSanimals and littermate controls at 2,4, and 7 days were 12, 10; 8, 6; and 20, 18, respectively. All animals were killed by decapitation 24 hr after the last dose. The livers were removed, weighed, and the activity of UDP-bilirubin GT (EC 2.4.1.17), GGTP (EC 2.3.2.2), and hepatic protein content were determined. CHRONIC ADULT EXPOSUREFifteen adult male Sprague Dawley rats weighing 200-250 g were given a 1% lead acetate tetrahydrate solution in their daily drinking water for 6-8 wk. The lead solution was offered ad libitum. At the end of the treatment period, the rats were killed by decapitation, the livers were removed, weighed, GT and GGTP ...

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Section: Discussionmentioning

confidence: 99%

Section: Speculationmentioning

confidence: 99%

Effect of Lead Exposure on the Activity of Some Hepatic Enzymes in the Rat

et al. 1979

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“…117 Exposure of mice to 1375, 137.5, or 13.75 ppm lead acetate in the drinking water resulted in each dose group in a significantly decreased number of antibody-forming cells to SRBC (IgM and particularly IgG); histopathological examination of the kidney disclosed a dose-related necrosis of tubular epithelial cells in the cortex. 118 In an extensive study by Trejo and co-workers 119 with adult rats that were given a single intravenous injection of 5 mg lead acetate, no effect was found on the primary and secondary antibody response to SRBC. A similar treatment with lead did, however, result in a significantly depressed intravascular clearance of colloidal carbon starting at 6 hr after lead treatment, thus contrasting with the enhanced susceptibility to endotoxin which occurs when lead and endotoxin are administered simultaneously.…”

Section: Lead and Cadmiummentioning

confidence: 98%

“…it does not seem likely that alteration in phagocytic function is a primary fact or in sensitivity to endotoxin. 106,119 As discussed by these authors, several factors, either alone or in combination, may elicit a cascade of reactions culminating in the death of the animal; these factors include impairment of the endotoxin detoxifying properties of macrophages (perhaps by inactivation of sulfhydryl-containing enzymes necessary for endotoxin inactivation) or hepatic parenchymal cell dysfunction by lead-induced liver injury. Lead exposure also increases, although less drastically, the vulnerability to several viral infections, most likely through reduced synthesis of interferon and not via inhibition of interferon action, as well as it increases the sensibility to infection with a Gram-positive microorganism.…”

Section: Lead and Cadmiummentioning

confidence: 99%

Immune Suppression as Related to Toxicology

Vos

2007

Journal of Immunotoxicology

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“…Trejo et al (1972) found that prior opsonization of the R-E test-lipid emulsion did not reverse lead-induced impairment of phagocytosis and concluded that a lack of opsonin was not the mediating factor in such dysfunction. Grafton and Di Luzio (1969) agreed that no stable, circulating plasma factor was involved in altered sensitivity to endotoxin.…”

Section: Introductionmentioning

confidence: 99%

Effects of subclinical lead exposure on the resistance of swine to challenge with Salmonella choleraesuis var Kunzendorf

Lassen

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Reticuloendothelial and hepatic functional alterations following lead acetate administration

Cited by 64 publications

References 20 publications

Effect of Lead Exposure on the Activity of Some Hepatic Enzymes in the Rat

Effect of Lead Exposure on the Activity of Some Hepatic Enzymes in the Rat

Immune Suppression as Related to Toxicology

Effects of subclinical lead exposure on the resistance of swine to challenge with Salmonella choleraesuis var Kunzendorf

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