Degeneration of mitochondria in lead poisoning

Watrach, A. M.

doi:10.1016/s0022-5320(64)80001-0

Cited by 60 publications

(13 citation statements)

References 14 publications

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“…It is conceiv able that this toxic action is also apt to destroy mitochondrial integrity [21], Apparent mitochondrial damages were not observed in livers of group L animals. The single dose of Ld was doubtlessly high in relation to the Ld uptake of living animals in a normal or Ld-polluted environment [13], but is in keeping with the well-established model in rats introduced by Selye et al [28], However, there are reports which indicate a destruction of hepatic mitochondria by re current administrations of Ld [35]. It is well evidenced that Ld has as strong affinity to hepatic mitochondria [13].…”

Section: Discussionmentioning

confidence: 58%

Derangement of Hepatic Energy Metabolism in Lead-Sensitized Endotoxicosis

1985

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Lead-sensitized endotoxicosis was investigated in rats in terms of hepatic energy metabolism. Lead acetate (Ld, 20 mg/kg BW) or endotoxin (Etx, 4 mg/kg BW) caused no deaths within 48 h. Ld plus Etx resulted in a lethality of 50 and 100% within 6 and 12 h respectively. Etx or Ld alone caused a slight but significant decrease in the hepatic tissue levels of total adenine nucleotides and/or ATP at 3 and 6 h after the application. The energy charge potential (ECP) remained normal. The ketone bodies acetoacetate and β-hydroxybutyrate and the ratio AcAc/β-OHB as well as the mitochondrial oxidative phosphorylation tended to increase; the hepatic tissue levels of pyruvate and lactate were increased after 3 h, indicative of an accelerated glycolysis. These alterations were no longer detectable after 6 h. In lead-sensitized endotoxemia (Ld + Etx), the total adenine nucleotides and ATP of the liver tissue decreased significantly to 84% (86%) and 71% (52%) of the controls within 3 and 6 h respectively, and the ECP had decreased from 0.865 to 0.684 at 6 h. The ketone bodies were increased, while the ratio AcAc/β-OHB was significantly decreased at 6 h. The hepatic tissue lactate remained elevated. The mitochondrial activity was significantly reduced. A hyperglycemia (175 mg·dl^-1) at 3 h changed into a hypoglycemia (50 mg·dl^-1) at 6 h. It is suggested that Ld plus Etx causes a rapid impairment of hepatic mitochondria which leads to a drastic disturbance of the hepatic energy metabolism including hypoglycemia and contributes to an enhanced lethality in Ld-sensitized endotoxicosis.

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Section: Discussionmentioning

confidence: 58%

Derangement of Hepatic Energy Metabolism in Lead-Sensitized Endotoxicosis

1985

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“…These inclusions have been frequently observed in human liver in such conditions as diabetes mellitus, viral hepatitis, hyperthyroidism, alcoholism, Wilson's disease, mucopolysaccharidosis, porphyria, obesity, chronic oral contraceptive use and chlorpropamide treatment (Reschel et al 1968;Laguens and Bianchi 1963;Svoboda and Manning 1964;Rubin and Lieber 1967;Haust 1968;Sternlieb 1968;Perez et al 1969;Lundbergh and Westman 1970;Mandel et al 1976Mandel et al , 1977. Intramitochondrial inclusions have also been reported in the liver of dogs, swine, rats and monkeys exposed to anoxia, ammonium, lead, alcohol, and steroids, and in protein deficiences (David and Kettle 1961;Carruthers and Steiner 1962;Watrach 1964;Ericsson et al 1966;Stein et al 1966;Ruffolo and Covington 1967;Tuchweber et al 1972). We would now add polybrominated biphenyl to the growing list of stimuli known to be associated with the observation of intramitochondrial inclusions in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…There have been reports of hepatic intramitochondrial crystalline inclusions in various laboratory animals after various treatments: in rats after ammonium intoxication (David and Kettle 1961) and after biliary obstruction (Carruthers and Steiner 1962); in swine after lead poisoning (Watrach 1964); and in protein deficient (Ericsson et al 1966) and mongrel street dogs (Stein et al 1966). More recently Boger et al (1979) described the presence of crystalline structures within hepatocyte mitochondria of rats treated with hexachlorobenzene.…”

Section: Introductionmentioning

confidence: 99%

The presence of hepatic intramitochondrial crystalline inclusions in polybrominated biphenyl-treated mice

et al. 1980

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Electron microscopic study of livers from mice fed 167 ppm polybrominated biphenyl (PBB) revealed mitochondrial abnormalities which consisted of both alterations in size and the formation of crystalline-like inclusions within the mitochondrial matrix. These inclusions appeared as parallel arrays of rods and were found in elongated mitochondria which contained few cristae. The findings are briefly described and the possible significance of such inclusions in relation to mitochondrial aberrations are discussed.

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“…Ultrastructural changes in liver have included intranuclear inclusion bodies (12), vacuolization, the presence of granular electron dense material, degenerative changes in Kupffer cells and hepatocytes, and proliferation of endoplasmic reticulum (14). Lead has a strong afflnity for mitochondria and is bound to the mitochondrial membrane producing swelling, lamellar bodies, and a reduced number of crystae (12,34).…”

Section: Discussionmentioning

confidence: 99%

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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Degeneration of mitochondria in lead poisoning

Cited by 60 publications

References 14 publications

Derangement of Hepatic Energy Metabolism in Lead-Sensitized Endotoxicosis

Derangement of Hepatic Energy Metabolism in Lead-Sensitized Endotoxicosis

The presence of hepatic intramitochondrial crystalline inclusions in polybrominated biphenyl-treated mice

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

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