B.D. Garg

Effect of cerium on the rat liver: an ultrastructural and biochemical study.

In rats, liver steatosis and necrosis were induced by cerous chloride (CeCl3) and the evolution of these changes was examined. By electron microscopy, 17 hours after CeCl3 treatment, dilation, disorganization and degranulation of the rough endoplasmic reticulum (RER) were noted with an increase in the number and electron density of lysosome-like bodies. In addition, nuclear chromatin showed showed a marked focal electron density, and the nuclear membrane appeared to be interrupted. At 24 hours, the RER was markedly dilated and degranulated, with free ribosomes aggregated in the cytoplasm. The Golgi cisternae appeared to be empty. There was an increase in the number and size of lipid droplets, with depletion of glycogen. At 48 hours, a massive proliferation of smooth endoplasmic reticulum (SER) vesicles occurred. Large lipid droplets were scattered throughout the cytoplasm, while the mitochondria displayed mild changes. By the 8th day, the number of lipid droplets returned to normal; no abnormalities were detected in the other cell organelles. Biochemically, the total hepatic ATP levels fell significantly by the 12th hour, dropping to a minimum by the 48th hour. The liver was gradually depleted of glycogen within the first 48 hours, while hepatic triglycerides increased rapidly, reaching a peak at 96 hours. Exogenous administration of adenine, ATP (adenosine triphosphate), or tryptophan completely prevented CeCl3-induced mortality; hepatic fat accumulation and necrosis were markedly decreased. Glucose, dl-methionine, and choline had no protective effect. It appears that a defect in hepatocellular lipoprotein synthesis and/or release may be responsible for lipid accumulation.

Ultrastructural changes induced by pregnenolone nitrile in the rat liver

JOHANNESSON, T. eC. WOODS, L. A. (1964). KAYMAKCALAN, S. & WOODS, L. A. (1956). LOH, H. H., SHE^, F. H. & WAY, E. L. (1969). SMITHS, S. E. & TAKEMORI, A. E. (1968). TIRRI, R. (1967). UNGAR, G. & COHEN, M. (1966). Br. J. Pharmac., 38, 157-170. In Scientific basis of drug dependence, Editor: Steinberg, H., pp. 77-86. London: J. and A. Churchill Ltd. Acta pharmac. tox., 21, 381-396. J. Pharmac. exp. Ther., 117, 112-116.

Intramitochondrial lamellar formations induced by pregnenolone-16-α-carbonitrile in the hepatocytes of pregnant rats

Electron microscopic study of the livers of pregnant rats given pregnenolone-16 α -carbonitrile revealed striking mitochondrial abnormalities which comprised alterations in shape, increases in size, and formations of lamellar arrays within the mitochondrial matrix. These structures were 50–110 A thick with a space of 160–200 A between them and were found in the elongated mitochondria which contained a few cristae. The diverse mechanisms of formation of intramitochondrial lamellae are discussed.

Effect of pregnenolone-16α-carbonitrile on the hepatic ultrastructure, glycogen content and ethylmorphine N-demethylase activity in pregnant, fetal, and newborn rats☆

Abstract Pregnenolone-16α-carbonitrile (PCN), a potent steroidal microsomal enzyme inducer, increased liver weight, depleted glycogen content, and markedly enhanced hepatic ethylmorphine N-demethylase activity in nonpregnant as well as in 18- and 21-day pregnant rats. Electron microscopy revealed extensive smooth-surfaced endoplasmic reticulum (SER) proliferation in the liver. Mitochondrial abnormalities were noted when the steroid was administered in the last stage of pregnancy. 14C-PCN or its derivative(s) was transported to the fetal liver. The steroid caused glycogen depletion without any detectable change in weight, ultrastructure, or ethylmorphine N-demethylation in the embryos liver. PCN treatment of neonates produced SER proliferation and significantly increased hepatic weight and enzyme activity. The steroid affected the hepatic tissue of nonpregnant, pregnant, and newborn rats but, except for its effect on glycogen content, it did not act upon the embryonic liver.

Fine Structural Changes in the Liver of Young and Old Rats as Influenced by Microsomal Enzyme Inducers

When given orally to young and old rats, pregnenolone-16 alpha-carbonitrile, spironolactone, or phenobarbital, known microsomal enzyme inducers, caused an increase in smooth endoplasmic reticulum. Dexamethasone, while a potent microsomal enzyme inducer, did not cause smooth endoplasmic reticulum increase. In both untreated and treated old rats, there was dilatation and vesiculation of rough endoplasmic reticulum with occasional granular material present in vesicles. Cytoplasmic lipid droplets of various sizes were frequent. Some mitochondria exhibited polymorphism and a variation in matrical density. Lysosomes and autophagic vacuoles as well as lipid droplets of various sizes were frequent in all groups. These results show that microsomal enzyme inducers influence the subcellular structure of hepatocytes in old rats.

Prevention of organomercurial intoxication by thyroid deficiency in the rat

Abstract In the rat, thyroparathyroidectomy or antithyroid drugs such as propylthiouracil and methimazole protect against acute poisoning with diphenyl or dimethyl (DMM) mercury. Though histologically thyroparathyroidectomy only slightly diminishes the early liver changes induced by DMM, it accelerates hepatic restoration processes. Serum glutamic-pyruvic transaminase activity and hexobarbital sleeping time, which are enhanced by DMM, are significantly decreased in thyroparathyroidectomized rats 48 hr after DMM administration. Kidney lesions are prevented by thyroid deficiency.

Effect of hypophysectomy on pregnenolone-16α-carbonitrile-induced ultrastructural changes in rat liver

SummaryPregnenolone-16α-carbonitrile (PCN) given orally to rats induces proliferation of the smooth-surfaced endoplasmic reticulum (SER) in hepatocytes, without producing marked alterations in other cell organelles. It appears that this steroid carbonitrile has a similar effect on the liver of hypophysectomized animals. Hypophysectomy alone causes a decrease of the SER.

Thioguanine-induced adrenocortical necrosis and its prevention by hypophysectomy in the rat. Light and electron microscopic study.

Abstract In rats, multiple injections of thioguanine produce hemorrhagic necrosis of the adrenal cortex. Electron microscopic studies and observations with the diffusion tracer horseradish peroxidase suggest that the primary lesion is at the level of capillary endothelial cells but a direct toxic action on adrenocortical cells cannot be excluded. Local intravascular platelet accumulation and aggregation as well as injury of adrenocortical cells seem to occur as a subsequent consequence of the endothelial changes induced by thioguanine. Hypophysectomy performed 7 days prior to the initiation of thioguanine treatment results in adrenocortical atrophy and complete prevention of adrenal apoplexy.

Effect of phenobarbital and steroids on phalloidin toxicity in rats

Abstract Experiments on rats indicate that both the hepatic damage and the mortality induced by phalloidin intoxication are inhibited by pretreatment with estradiol. Other steroids [e.g. spironolactone, ethylestrenol, progesterone, pregnenolone-16α-carbonitrile (PCN)], glucocorticoids and phenobarbital are ineffective in this respect. Since these compounds increase certain hepatic microsomal enzyme activities but do not modify phalloidin toxicity, it is unlikely that the toxin is metabolized by the particular enzyme systems that they activate.

Prevention of phalloidin intoxication in rats by partial hepatectomy

In rats, the hepatic injury and mortality elicited by an intraperitoneal injection of phalloidin are prevented by partial hepatectomy performed 1, 3, 4 or 5 days earlier.ZusammenfassungPartielle Leberresektion, die 1, 3, 4 oder 5 Tage vor i. p. Injektion von Phalloidin durchgeführt wird, verhindert in Ratten die durch diesen Stoff bedingte Leberschädigung und Mortalität.