K. Kovacs

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.

Prevention by Spironolactone of 7,12-Dimethylbenz(a)anthracene-induced Adrenal Necrosis

Summary Administration of spironolactone protects the rat against 7,12-dimethylbenz (a) anthracene-induced adrenal necrosis.

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.

Suppression by spironolactone of 7,12-dimethylbenz(a)anthracene-induced mammary tumors

Abstract Pretreatment with spironolactone, an antimineralocorticoid steroid lactone, delays the development and decreases the incidence and yield of 7,12 -dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats. The mechanism of this suppressive action is not fully understood but on the basis of some recent findings it seems reasonable to suppose that spironolactone is capable of influencing the intermediary metabolism of DMBA by inducing or stimulating microsomal enzymes in the hepatocytes which convert the carcinogen into inactive derivatives. Direct evidence is still lacking but the problem warrants further study primarily because spironolactone, in contrast to the other microsomal enzyme inducers, is a non-toxic compound which can be administered for a considerable length of time without serious consequences.

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.

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.

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.