Studies on carbon tetrachloride intoxication

Smuckler, Edward A.; Iseri, Oscar A.; Benditt, Earl P.

doi:10.1016/0006-291x(61)90161-9

Cited by 63 publications

(14 citation statements)

References 3 publications

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“…5). In accordance with the reports of Smuckler et al, 17 protein synthesis is markedly depressed during the first 15 hr of intoxication. A "peak" of label incorporation was observed between 30 and 40 hr., which precedes any observable or measurable functional restoration.…”

Section: Figsupporting

confidence: 92%

Restoration of hepatic mitochondria during recovery from carbon tetrachloride intoxication

Brabec

Gray

Bernstein

1974

Biochemical Pharmacology

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Abstract--During CC14 intoxication in rats, a disruption of hepatic mitochondrial structure and function occurs, which is characterized by a loss of respiratory activity, loss of phosphorylation coupled to respiration, and mitochondrial swelling, attended by loss of cristae structure. Within 15-25 hr, after full development of the mitochondrial lesion, the function and structure of the mitochondria are largely restored. Studies of the turnover of mitochondrial DNA and the rates of synthesis of mitochondrial DNA and protein indicated that the CC14-insulted hepatocyte is repairing the mitochondrial damage by the insertion of specific elements into the damaged organelle, rather than by proliferation of undamaged mitochondria for replacement. The failure of ethidium bromi~e, oxytetracycline and chloramphenicol, specific inhibitors of mitochondrial protein, and/or nucleic acid synthesis, to block this restoration substantiates the postulated repair process, and also indicates the non-critical nature of the respective mitochondrial functions during the repair process. Cytochrome measurements made during the period of acute damage revealed normal levels of cytochrome c, c~ and aa a. The observed elevation of cytoehrome b is attributed to contamination of the preparation by hemoglobin.THE HEPATIC mitochondrion is one of the characteristic sites of CC14-induced cell damage. 1 Ultrastructurally, the mitochondria of an intoxicated animal appear to be swollen in situ, and the matrix is abnormally lucid. 2 The mitochondria are calcium loaded, and amorphic, dense bodies, probably aggregations of calcium phosphate, are noted in the matrix of the swollen organelles, a The altered in situ appearance is accompanied by a loss of respiratory activity, especially on NAD ÷ -linked substrates, and by an impairment of energy-coupled functions, which is detectable when isolated mitochondria are assayed. 4 This lesion is not necessarily associated with lethality, since the lesion can be developed by a dose of CC14 from which the animal recovers. Under such conditions, mitochondrial degeneration ceases and a return of normal structure and function is observed.Of interest to this laboratory is the route by which the CC14-damaged hepatocyte affects the restoration of its damaged mitochondria. In consideration of recent proposals related to mitochondrial biogenesis, it is necessary to consider a minimum of three possible routes of restoration: (1) Replacement of damaged organelles. Since it is possible that all mitochondria within a surviving hepatocyte have not suffered massive damage, a replicative burst of mitochondrial biogenesis by the slightly damaged, or undamaged mitochondria could serve to replenish the mitochondrial B,P. 23/23--A 3227

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Section: Figsupporting

confidence: 92%

Restoration of hepatic mitochondria during recovery from carbon tetrachloride intoxication

Brabec

Gray

Bernstein

1974

Biochemical Pharmacology

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“…In the histological and histochemical study on the liver of rats treated with CC14 (22), enzymatic alteration is seen prior to the appearance of the histological change revealed by hematoxylin and eosin stain. The alteration produced by CCl4 in the rough endoplas mic reticulum suggested that there might be a defect in protein synthesis (23). Electron micrograph showed a widespread dislocation of the ribonucleoprotein particles from the membranes of the rough endoplasmic reticulum, and simultaneous decrease in amino acid incorporation rate reflects depressed synthesis of protein by the liver (24).…”

Section: Discussionmentioning

confidence: 99%

Effect of Carbon Tetrachloride Upon Arylesterases in Mice

Takahashi

Nakazawa

Watanabe

1970

Japanese Journal of Pharmacology

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Early works by Augustinsson (1-4) demonstrated that three types of esterases exist in vertebrate plasma in regard to substrate specificity and susceptibility to selective inhi bitors, and he classified them into arylesterases [EC 3. 1. (5) suggested that decrease in the activity of phenyl acetate esterase (corre sponding to arylesterases, according to the Augustinsson's classification) was correlated with the degree of liver damage and that, clinically, the activity of the enzyme in serum decreased greatly in the case of liver cirrhosis. In the present paper, changes in the total activity and the electrophoretic pattern of arylesterases were studied in CC14-induced mouse liver injury using fl-naphthyl acetate as substrate. METHODSExperiment I: Effect of CCl4 administration upon electrophoretic pattern of arylesterases in liver 12,000 X g supernatant and serum Male inbred mice of the NC strain weighing 20 to 24 g were divided into 7 groups of 5 animals each, and treated with 1 ml/kg of CC14 in trap eritoneally except the control group. They were sacrificed at 1/4, 3, 6, 24, 48 and 72 hours after CCI4 injection by ex sanguination from the femoral artery. The liver was immediately removed, rinsed with ice-cold physiological saline and homogenized with an equal amount of 0.05 M phosphate buffer, pH 7.4, by a glass homogenizer with a teflon pestle under refrigeration . The subsequent procedures were performed at fC. The homogenate was centrifuged for 45 minutes at 12,000 X g and the supernatant was separated. The blood collected was also centrifuged for 15 minutes at 3,000 r.p.m. to obtain serum.Thin-layer agar gel electrophoresis described by Ogita (6-8) was performed for 2 hours with the constant current adjusted to 1 mA/cm to separate arylesterases in the super natant of liver homogenate and serum. After electrophoresis, the glass plate covered with agar gel film was immersed into phosphate buffer, pH 6.8, containing Q-naphthyl acetate as substrate and naphthanyl diazo blue B and kept at 37°C for 20 minutes. The

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“…The question of whether the retransport of fat out of the liver is impaired in choline deficiency has been examined in intact rats [Olson et al, 1958;Lombardi and Recknagel, 1962] but there is no agreement on this point, In fatty livers produced by ethionine or carbon tetrachloride, there appears to be a defect in plasma protein and lipoprotein synthesis [Smuckler et al, 1961;Robinson and Harris, 1961] and this is thought to be significant in terms of fat transport from the liver [cf. Olson and Vester, 1960].…”

Section: Discussionmentioning

confidence: 99%

The Metabolism of Free Fatty Acids and Chylomicron Triglycerides by the Perfused Choline‐deficient Rat's Liver

Mishkel

Morris

1964

Exp Physiol

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Experiments were carried out with isolated perfused livers from cholinedeficient rats to study the uptake and metabolism of free 14C‐palmitic acid and 14C‐labelled chylomicron triglycerides. The livers from choline‐deficient rats took up both these forms of fat from the perfusate as rapidly as did normal livers. There was no significant difference in the amount of radioactivity recovered from the liver lipids in choline‐deficient and normal livers but there was a significantly higher incorporation of labelled fatty acids into the noncholine‐containing phosphatides in the choline‐deficient livers. Both normal and choline‐deficient livers retransported labelled fatty acids into the perfusate as esterified fat. There was a lower incorporation into perfusate triglycerides and a higher incorporation into perfusate phospholipids in choline‐deficient livers. In both groups of experiments, some free fatty acids were also released into the perfusate from the liver. The oxidation of both free fatty acids and chylomicron triglycerides occurred readily in choline‐deficient livers. The specific activity of the CO2 produced by choline‐deficient livers from fed rats was significantly higher than that produced by livers from fed normal rats.

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Studies on carbon tetrachloride intoxication

Cited by 63 publications

References 3 publications

Restoration of hepatic mitochondria during recovery from carbon tetrachloride intoxication

Restoration of hepatic mitochondria during recovery from carbon tetrachloride intoxication

Effect of Carbon Tetrachloride Upon Arylesterases in Mice

The Metabolism of Free Fatty Acids and Chylomicron Triglycerides by the Perfused Choline‐deficient Rat's Liver

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