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At least 19 recordsLinked to original sources
PubMed1977

DNA replication in Physarum polycephalum: characterization of DNA replication products made in vivo in the presence of cycloheximide in strains sensitive and resistant to cycloheximide.

Synchronous plasmodia of cycloheximide-sensitive and cycloheximide-resistant strains of Physarum polycephalum were labelled with 3[H]-deoxyadenosine in pulse and pulse-chase experiments in presence and absence of cycloheximide. The replication products were studied with alkaline sucrose gradient sedimentation analysis. We show that the action of cycloheximide on DNA replication in Physarum is mediated through the ribosome, since the ribosomally located resistance also makes the plasmodial DNA replication refractile to the action of cycloheximide. Cycloheximide caused inhibition of three stages in DNA replication in the wild type: first, the formation of primary replication units ("Okazaki" size fragments), secondly, the ligation of primary units into secondary ("Replicon" size) units and thirdly, the ligation of secondary units into mature DNA.

Centrifugation, Density Gradient↗
PubMed1975

Cycloheximide production by Streptomyces griseus: control mechanisms of cycloheximide biosynthesis.

Cycloheximide accumulation in a fermentation medium has been shown to be the product of the balance between synthesis and degradation of this antibiotic. Glucose has been shown to prevent cycloheximide degradation. Cycloheximide has been shown to interfere with its own synthesis probably due to feedback inhibition. Approaches for increasing cycloheximide titers in the light of these findings are discussed.

Cycloheximide↗
PubMed1979

Nuclear requirement of post-maturational cortical differentiation of amphibian oocytes: effects of cycloheximide.

Cycloheximide induced a complex series of alterations in the cortical cytoplasm of amphibian (Rana pipiens) oocytes undergoing steroid induced nuclear and cytoplasmic maturation in vitro. The morphological changes were described and the role of nuclear-cytoplasmic interactions in the induction of these changes was investigated in intact, enucleated and enucleated-reinjected oocytes. Three stages of cortical changes were ascertained on the basis of: localized alterations at the animal pole, redistribution of pigment and localized contractility (furrow formation) primarily along the animal:vegetal pole axis. The extent and type of cortical alterations varied depending upon the time at which oocytes were examined following hormonal stimulation and cycloheximide treatment. Cycloheximide did not produce cortical alterations in non-hormone treated oocytes nor in steroid treated oocytes until after germinal vesicle breakdown. Nuclear and cytoplasmic maturation and the appearance of cortical alterations were all inhibited when cycloheximide was added to oocytes at the time of steroid treatment. Cycloheximide induction of cortical alterations occurred only after the inhibitor was no longer effective in preventing germinal vesicle breakdown. Enucleated oocytes underwent cytoplasmic maturation in response to the steroid but exhibited no cortical alterations following the delayed addition of cycloheximide. Simultaneous administration of cycloheximide and steroid to enucleated oocytes inhibited cytoplasmic maturation and all observable cortical alterations. Reinjection of nuclear material into enucleated oocytes restored the ability of cycloheximide to induce cortical alterations following steroid induction of cytoplasmic maturation. Without steroid treatment, such reinjected oocytes did not exhibit cortical changes in response to cycloheximide. The data demonstrate that the nucleus is required for and contains a factor(s) which controls the cycloheximide response and post-maturation differentiation of the oocyte. The maturational changes in the cortical cytoplasm appear to be dependent on the intermixing of the germinal vesicle nucleoplasm materials with mature cytoplasm following germinal vesicle breakdown. The results further suggest that the cortical effects of cycloheximide are dependent upon the initiation of protein synthesis during this period of oocyte development. The significance of these observations and experimental studies are discussed in relation to current understanding of the molecular mechanisms controlling meiosis induction and the composition of the germinal vesicle.

Animals↗
PubMed1975

Synthesis of reovirus-specific polypeptides in cells pretreated with cycloheximide.

When L cells are infected with reovirus in the presence of cycloheximide neither virus-specific polypeptides nor viral double-stranded RNA are synthesized. There is some synthesis of viral single-stranded RNA, transcribed mainly from segments L1, M3, S3, and S4 of the 10 viral genomic segments, and in previous work this has been termed the early mRNA pattern. In an attempt to determine whether these early transcripts are functional mRNA's, the transcripts were allowed to accumulate for a period of 17.5 h at 31 C in cycloheximide-treated cells. The cycloheximide was removed and the cells were exposed for various periods to radioactive amino acids to label any virus-specific polypeptides that might be synthesized. An immunoprecipitation technique was used to separate the viral polypeptides from cellular extracts and this precipitate was then analyzed on sodium dodecyl sulfate-polyacrylamide gels. Within 30 min of cycloheximide removal, four major polypeptides (lambda2, mu0, sigma2a, and sigma3) and two minor polypeptides (lambda1 and mu2) were found. In infected cells without cycloheximide eight viral polypeptides (lambda1, lambda2, mu0, mu2, sigma1, sigma2, sigma2a, sigma3) were found at 17.5 h after infection and the same pattern was found between 3 to 4 h after removal of cycloheximide which had been present for 17.5 h after infection. The latter result shows that the cycloheximide inhibition is reversible and that the cells readily recovered and synthesized the normal complement of viral polypeptides. In one set of experiments cordycepin was added to infected cells immediately after the removal of cycloheximide at 17.5 h to inhibit the synthesis of new viral transcripts. During the succeeding 4 h in the presence of cordycepin, the pattern of protein synthesis was the same as that obtained during the 30 min after cycloheximide removal. It is concluded that the polypeptides formed right after removal of cycloheximide are the translation products of transcripts accumulated during cycloheximide treatment and, therefore, that these transcripts are functional viral mRNA's.

Cycloheximide↗
PubMed1975

Influence of cycloheximide on the lung.

We examined the time course of the influence of cycloheximide on descending pressure-volume curves of excised lungs and on protein and lecithin synthesis and oxygen consumption by lung slices. We also looked at the influence of cycloheximide on granular pneumocyte ultrastructure. Excised lungs from cycloheximide-treated animals are more compliant than controls. After ventilation with air, lungs from control and cycloheximide animals show increased retractive forces and a shift to the right of the deflation P-V curve. Incubation at 38 degrees C for 30 min reverses these changes in control lungs, but not in lungs from cycloheximide-treated rabbits. There is no change in liquid delfation P-V curves after cycloheximide. Cycloheximide causes an immediate decrease of 50% in incorporation of radioactive leucine into protein by lung slices. Incorporation of radioactive palmitate into lecithin and oxygen consumption are also decreased by 50% 6 h after cycloheximide. Lamellar bodies in granular pneumocytes are smaller after cycloheximide. Cycloheximide causes a significant increase in the surface density of the lamellar body envelope. Cytoplasmic area of granular pneumocytes is increased after cycloheximide.

Animals↗
PubMed1992

Superinduction of c-fos gene expression by estrogen in cultured guinea-pig endometrial cells requires priming by a cycloheximide-dependent mechanism.

The c-fos gene expression is rapidly induced by various mitogenic agents and protein synthesis inhibitors in many cell types. Estradiol-17 beta can induce c-fos gene expression in breast cancer cell lines and in the uterus in vivo, but not in cultured guinea-pig endometrial cells. Using this model, we investigated whether a protein synthesis inhibitor, cycloheximide, could induce the c-fos gene and permit a superinduction by estrogens. In the presence of cycloheximide (10 micrograms/ml), protein synthesis was inhibited at 95% within the first hour. From 190 min after the addition of estradiol-17 beta or diethylstilbestrol (10(-8) M) and cycloheximide (10 micrograms/ml), there was a significant increase (ranging from 3- to 5-fold) of the c-fos messenger RNA level (2.2 kilobase in size), compared with the level in cells treated with cycloheximide alone. Nonestrogenic steroid hormones and estradiol-17 alpha were unable to induce c-fos gene expression in the presence of cycloheximide. The effect of estradiol-17 beta observed in the presence of cycloheximide was completely abolished by 4-hydroxy-tamoxifen or by Ly 156758 or by ICI 164384 (10(-6) M). The c-fos mRNAs were rather stable in cells treated with cycloheximide for 2 h (half-life = 51 +/- 6 min) and there was no further increase in the c-fos messenger RNA stability after the addition of cycloheximide plus estradiol-17 beta (half-life = 40 +/- 3 min). The overall results suggest a response at the transcriptional level. In conclusion, cycloheximide transmits activating signals to the c-fos gene which act as priming elements to allow the estrogen action in cultured guinea-pig endometrial cells.

Androstenedione↗
PubMed1977

HeLa cell DNA polymerases: the effect of cycloheximide in vivo and detection of a new form of DNA polymerase alpha.

Blockage of protein synthesis in HeLa cells by cycloheximide leads to selective effects on the levels of DNA polymerases alpha, beta, and gamma in the cell. The total activity of DNA polymerase alpha remains unchanged after 7 h exposure of cells to cycloheximide but drops to 50% of its original level after 24 h. The level of the beta-polymerase falls rapidly in the cell and is reduced to less than 30% of its initial value by 7 h after treatment of the cells with cycloheximide. The gamma-polymerase level is diminished by 30--40% during the 7 h cycloheximide treatment and reaches 50% of its original level after 24 h. Cells which have been exposed to cycloheximide for 7 h will regain normal levels of the beta- and gamma-polymerases within 90 min after removal of the drug. The cycloheximide-treated cells also show the presence of a new form of the alpha-polymerase, designated alpha1, which can be clearly detected as a separate entity in column chromatography. The level of alpha1 in the nucleus increases during the period that the cells are treated and cycloheximide so that after 24 h it represents almost 50% of the nuclear DNA polymerase activity. The presence of alpha1 in the cytoplasmic fraction can also be demonstrated in both cycloheximide-treated and normal, growing cells.

Cell Nucleus↗
PubMed1975

Nature of the increase in renal ornithine decarboxylase activity after cycloheximide administration in the rat.

The present study was designed to determine whether the increase in rat renal ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity after cycloheximide administration was a primary effect on the kidney or was a secondary effect of adrenal or pituitary hormones released in response to the drug. Renal ornithine decarboxylase activity was reduced approximately 70% 1 hr after intraperitoneal administration of doses of cycloheximide that also inhibited renal protein synthesis by 68-95% within 1 hr. Protein synthesis began to recover by the second hour, accompanied by a rise in decarboxylase activity that reached a peak about six times greater than pretreatment values at 8 hr, then gradually declined to preinjection levels by 16 hr. Peak ornithine decarboxylase activity was directly proportional to cycloheximide doses up to 250 mug; larger doses, which almost abolished protein synthesis for 8 hr, where inhibitory. Plasma corticosterone rose rapidly after cycloheximide, reached a peak at 2 hr, then fell to baseline by 8 hr. Corticosterone response was also dose-dependent up to 250 mug, but larger doses were inhibitorymadrenalectomy did not reduce decarboxylase activity response to cycloheximide, nor did cortisol administration enhance it. Hypophysectomy greatly reduced baseline renal decarboxylase activity within 9 hr and all but abolished the increase in enzyme activity normally seen after cycloheximide administration to the intact rat. The hypophysectomized animal exhibited apparent increased sensitivity to cycloheximide, since a smaller dose of the drug caused a reduction in renal protein synthesis similar to that seen with a larger dose in the intact rat. As protein synthesis was recovering in the hypophysectomized animals, renal decarboxylase activity responded adequately to the injection of a crude pituitary extract. These data suggest that renal ornithine decarboxylase turnover is rapid, that baseline activity is.maintained by new protein synthesis, and that the increase in renal enzyme activity after cycloheximide is in larger part dependent upon pituitary hormone action.

Adrenal Glands↗
PubMed1992

Cycloheximide protection against actinomycin D cytotoxicity.

Pretreatment plus concomitant treatment with 10 micrograms/ml cycloheximide protected Chinese hamster ovary cells and Swiss 3T3 cells against the cytotoxicity of actinomycin D. The cycloheximide treatment reduced the intracellular concentration of actinomycin D by reducing the level of actinomycin D bound to the acid precipitable fraction of the cell. Levels of unbound actinomycin D were unaffected by cycloheximide, indicating that the plasma membrane permeability to AD was not reduced. Actinomycin D inhibited total transcription but did not reduce cytoplasmic levels of rRNA nor of most tested mRNA; however, cytoplasmic levels of c-myc mRNA were reduced below detectability. Cycloheximide treatment further inhibited total transcription and had no effect on cytoplasmic levels of rRNA nor of most tested mRNA. Cytoplasmic levels of c-myc were elevated by cycloheximide and remained so even in the presence of actinomycin D. These data suggested that a reduction in cytoplasmic levels of short lived, essential mRNA, such as c-myc mRNA, was one lethal lesion of actinomycin D. Furthermore, cycloheximide's protection may result, in part, from its ability to stabilize and/or elevate cytoplasmic levels of these mRNA, thus counteracting their depletion by actinomycin D. Protection may also result from the cycloheximide-induced reduction of actinomycin D bound to the acid precipitable fraction of the cells.

Animals↗
PubMed1977

Cycloheximide produces adult-like retention deficits of prior learning in infant mice.

Utilizing a dosage of cycloheximide which was found to inhibit cerebral protein synthesis by almost 90% after injection, separate groups of 13-day-old mice received either cycloheximide or saline followed by 0 (control), 15, or 25 training trials in a discriminated shock-escape T-maze. Twenty-four hr later, each mouse was treated with cycloheximide or saline and tested for retention by an additional 25 trails in the T-maze. As reflected by correct choice-point turns, the results suggest that whereas salinetreated mice demonstrated reliable retention of prior learning, cycloheximide treated mice exhibited memory impairment; cycloheximide per se had no effect on performance during either original training or retest. A final experiment indicated that this memory impairment was not due to cycloheximide's general debilitating side effects at the time of retention testing. Taken together, these data suggest that protein synthesis inhibition during training impaired consolidation and/or retrieval processes involved in memory. The biochemical and behavioral effects following cycloheximide injection in 13-14-day-old mice in the present study parallel those reported with adult animals and lend indirect support to the hypothesis that the 24-hr memory capacity exhibited by these young mice reflects the early functioning of those processes involved in adult long-term memory.

Amnesia↗
PubMed1979

Inhibition by cycloheximide of degradation of cytochrome P-450 in primary cultures of adult rat liver parenchymal cells and in vivo.

Degradation of cytochrome P-450 was studied in adult rat liver parenchymal cells in primary monolayer culture. In cells incubated in standard culture medium, the amount of cytochrome P-450 decreased at an accelerated rate relative to either the rate of degradation of total protein in the cells or the turnover of cytochrome P-450 in vivo. This change was succeeded by a spontaneous increase in the activity of haem oxygenase, an enzyme system that converts haem into bilirubin in vitro, measured in extracts from the cultured cells. This finding suggests that the rate of cytochrome P-450 breakdown may be controlled by factor(s) other than the activity of haem oxygenase. The decline in cytochrome P-450 and the subsequent increase in haem oxygenase activity was prevented by incubation of hepatocytes in medium containing an inhibitor of protein synthesis such as cycloheximide, puromycin, actinomycin D, or azaserine. The effect of cycloheximide appeared to be due to decreased breakdown of microsomal (14)C-labelled haem. By contrast, cycloheximide was without effect on the degradation of total protein, measured either in homogenates or in microsomal fractions prepared from the cultured cells. These results suggest that the conditions of cell culture stimulate selective degradation of cytochrome P-450 by a process that is inhibited by cycloheximide and hence may require protein synthesis. The findings in culture were verified in parallel studies of cytochrome P-450 degradation in vivo. After administration of bromobenzene, the degradation of the haem moiety of cytochrome P-450 was accelerated in vivo in a manner resembling that observed in cultured hepatocytes. Administration of cycloheximide to either bromobenzene-treated rats or to untreated rats decreased the degradation of the haem moiety of cytochrome P-450. However, the drug failed to affect degradation of haem not associated with cytochrome P-450, suggesting that cycloheximide is not a general inhibitor of haem oxidation in the liver. These findings confirm that the catabolism of hepatic cytochrome P-450 haem is controlled by similar cycloheximide-sensitive processes in the basal steady state in vivo, as stimulated by bromobenzene in vivo, or in hepatocytes under the conditions of cell culture. We conclude that the rate-limiting step in this process appears to require protein synthesis and precedes cleavage of the haem ring.

Animals↗
PubMed1979

Influence of cycloheximide on normal and induced delta-aminolevulinic acid synthetase (aminoketone synthesis) of rat liver in vivo and in vitro.

2 and 5 mg/kg cycloheximide given i.p. 30 minutes prior to the inducer allylisopropylacetamide (AIA) diminished or prevented the enhancement of delta-aminolevulinic acid synthetase (ALAS) activity in newborn rats. In adult rats the small AIA effect 24 hours after pretreatment was enhanced by 2 mg/kg cycloheximide i.p., when the inhibitor was injected 2 hours prior to the inducer. The basic aminoketone synthesis was inhibited by cycloheximide alone. 150-600 microgram/ml cycloheximide had no effect on the aminoketone synthesis of rat liver slices in vitro during 4 hours of incubation. The in vitro induction by 0.6 mg/ml AIA was enhanced by cycloheximide, if the inducer was added 1 hour after preincubation with cycloheximide. It is supposed, that the cytoplasmically localized precursor-ALAS is activated at the beginning of the induction process prior to the initiation of de novo enzyme synthesis, at least in vitro.

5-Aminolevulinate Synthetase↗
PubMed1976

The effect of cycloheximide on hepatic RNA synthesis and nucleolar size in rats force-fed a threonine-devoid diet.

Young rats were force-fed a complete or threonine-devoid diet for 3 days. On the fourth morning, rats of each group were injected intraperitoneally with cycloheximide (150 mug/100 g body weight) or saline with [6-14C]orotic acid 30 minutes later, 2 hours before killing. Incorporation of [6-14C]orotic acid into hepatic RNA fractions (whole homogenate, postmitochondrial supernatant, microsomes, ribosomes, nuclei and soluble) revealed elevated levels (cpm/mg RNA) in rats force-fed the threoninedevoid diet in comparison to those of rats force-fed the complete diet. However, treatment with cycloheximide decreased the incroporation of [6-14C]orotic acid into the hepatic RNA fractions of the rats force-fed the threonine-devoid diet to levels that were similar to those in rats force-fed the complete diet with or without cycloheximide treatment. Studies dealing with nucleoli isolated by sucrose gradients from livers of control and experimental rats revealed heavier nucleoli and more radioactive labeled RNA in nucleoli ([6-14C]orotic acid administered 30 minutes before killing) of rats force-fed the threonine-devoid diet than in those force-fed the complete diet for 3 days. Treatment with cycloheximide decreased the elevated incorporation in the experimental rats. Also, electron microscopic studies revealed that after cycloheximide treatment, the enlarged hepatic nucleoli of the experimental rats became smaller and returned to a more normal pattern, as found in the control rats. The studies suggest that active hepatic protein synthesis is involved in the increased hepatic RNA synthesis in rats force-fed the threonine-devoid diet and that following inhibition of protein synthesis, as induced by cycloheximide, there is a rapid inhibition of the accelerated hepatic RNA synthesis observed in rats force-fed the threonine-devoid diet with a rapid reversal toward a normal level, i.e. toward that found in control rats.

Animals↗
PubMed1978

Resistance of selected saprobic and zoopathogenic fungi to cycloheximide.

Spore germination was used as an assay to measure the sensitivities of selected fungi (Achlya bisexualis, Cladosporium sp., Trichophyton mentagrophytes and Microsporum gypseum) to cyclohexamide and to determine their abilities to adapt to the drug. Two patterns of response were noted. The saprobes, A. bisexualis and Cladosporium sp., demonstrated acquired resistance. Spores from hyphae previously exposed to cycloheximide either germinated in the presence of concentrations of the drug that completely inhibited spores from unexposed hyphae (Achlya), or germinates with a shorter lag and to a greater extent in the presence of the antibiotic than did spores from unexposed hyphae (Cladosporium). Hyphae of Achlya adapted at concentrations of cycloheximide in which spores did not germinate and hyphae of Cladosporium adapted more rapidly than spores. Achlya adapted to only 12 muM-cycloheximide whereas Cladosporium acquired resistance to 18 mM-cycloheximide. These fungi lost this acquired resistance after a single transfer to media lacking cycloheximide. The zoopathogens, T. mentagrophytes and M. gypseum, had a contrasting response, indicating constitutive resistance. Conidia from unexposed hyphae showed 90 to 100% germination on media containing up to 18 mM-cycloheximide; prior exposure to the drug did not affect their response.

Adaptation, Physiological↗
PubMed1977

Study of protein synthesis in rat liver mitochondria use of cycloheximide.

1. The effects of short-term and long-term administration of cyclohexidine on rat liver mitochondrial protein synthesis have been examined and were found to be different. 2. Long-term administration of cycloheximide resulted in inhibition of total cellular protein synthesis including that of mitochondria while, at short-term intervals, 8-10% of mitochondrial protein synthesis was cycloheximide-resistant. 3. The inhibitory effect was also reflected in terms of protein synthesizing ability of mitochondria in vitro, the inhibition becoming apparent at 40 min and showing progressive increase with time. 4. The observed inhibition of mitochondrial protein synthesis by cycloheximide was not due to either inhibition of energy metabolism or alteration of amino-acid pool. 5. Cycloheximide did not enter mitochondria or sonic preparation under conditions in vitro. On the other hand, after administration of [3H]cycloheximide, significant quantities of the label were found to be associated with mitochondria and mitoribosomes. 6. These results indicated that cycloheximide reached the site of action in mitochondria under conditions in vivo but was unable to do so in vitro. 7. The results are discussed to elucidate the possible mechanisms involved in the inhibition of truly mitochondrial protein synthesis by cyclohexamide.

Amino Acids↗
PubMed1990

[Effects of DEAE-dextran, centrifugation, cycloheximide and their combination on infection and growth of Chlamydia psittaci bird isolates].

In order to establish a stable and uniform cultural method in a cell line HaLa 229, we studied the effect of DEAE-dextran, centrifugation, cycloheximide and their combination on infectivity and progeny yields of Chlamydia psittaci isolated mainly from birds. Of 11 strains (10 avian and one human origin Ito strain), 9 showed maximal inclusion formation when host cells were treated with a combination of dextran and cycloheximide. Of the other two strains, one showed maximum inclusion formation with dextran alone and any treatments did not enhance the inclusion formation in another strain. Maximal yields of progeny at 48 hours after infection was observed in 5 (4 avian and Ito) strains when host cells were treated with a combination of dextran and cycloheximide. One avian strain showed maximal yields with a triple treatment; dextran and cycloheximide combined with centrifugation. At 72 hours after infection, three avian and Ito strains showed maximal yields with a double treatment (dextran and cycloheximide) and other two avian strains showed that with a triple treatment (double treatment added with centrifugation). The results suggest that in a cell culture HeLa 229, the treatment with dextran and cycloheximide may provide an efficient isolation and growth pattern for most strains originated from birds.

Animals↗
PubMed1975

DNA replication in SV40-infected cells. XI. The properties of SV40 DNA and nucleoprotein complex synthesized in the presence of cycloheximide.

Cycloheximide inhibits simian virus 40 (SV40) DNA synthesis in productively infected African green monkey kidney cells. The residual viral DNA synthesized in the presence of this drug is deficient in superhelical turns as measured by band sedimentation in the presence of several concentrations of ethidium bromide. The superhelical density of SV40 DNA synthesized in the presence of cycloheximide is about one half that of viral DNA produced in the absence of this drug. Ribonuclease H and alkali treatment were employed to determine if ribonucleotides could be detected in closed circular SV40 DNA synthesized in the presence of cycloheximide. While both these approaches detected ribonucleotides in mitochondrial DNA, no identification of ribonucleotides in SV40 DNA synthesized in the presence of cycloheximide was found. The SV40 nucleoprotein complex synthesized in the presence of cycloheximide has a slower sedimentation rate (35S) and a higher bouyant density (1.54 g/cm3) than the complex made in the absence of this drug (50S; 1.47 g/cm3). The protein:DNA ratio of the SV40 nucleoprotein complex is normally about 0.9. This ratio is reduced to about 0.6 when the complex is synthesized in the presence of cycloheximide.

Cell Line↗
PubMed1976

Modification of the hepatotoxicity of D-galactosamine in the rat by cycloheximide.

The effect of cycloheximide (1.5 mg/kg), a potent inhibitor of protein biosynthesis, on D-galastosamine (375 mg/kg)-induced hepatic necrosis and hepatic triglyceride accumulation was studied in rats. Serum transaminase levels, 24 hr after D-galactosamine administration, were significantly reduced in animals treated simultaneously or 4 hr before D-galactosamine with cycloheximide, when compared to animals given D-galactosamine alone. Transaminase levels in rats given cycloheximide 4 hr after D-galactosamine were not reduced. Histological grading of hepatocyte necrosis showed a similar pattern of protection in the pretreated and simultaneously treated groups. Hepatic triglycerides were significantly reduced only in the latter group. Fatality 48 hr after D-galactosamine administration was significantly less common in rats pretreated with cycloheximide when compared to rats given D-galactosamine without cycloheximide, and surviving animals in the cycloheximide pretreated group had a lower serum transaminase level, a lower necrosis score, and a reduced hepatic triglyceride level. These data are consistent with the concept that protein synthesis is important in the pathogenesis of D-galactosamine-induced hepatotoxicity.

Alanine Transaminase↗