Studies on the mitoinhibitory effects of orotic acid on normal rat liver and hepatic nodules by Aisha Sheikh

Cover of: Studies on the mitoinhibitory effects of orotic acid on normal rat liver and hepatic nodules | Aisha Sheikh

Published by National Library of Canada = Bibliothèque nationale du Canada in Ottawa .

Written in English

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Edition Notes

Book details

SeriesCanadian theses = Thèses canadiennes
The Physical Object
FormatMicroform
Pagination2 microfiches : negative.
ID Numbers
Open LibraryOL15085878M
ISBN 10031583319X
OCLC/WorldCa30810377

Download Studies on the mitoinhibitory effects of orotic acid on normal rat liver and hepatic nodules

Orotic acid (OA), a promoter of liver carcinogenesis, inhibited proliferation of primary hepatocytes in culture as monitored by labelling index, mitotic index and total DNA content. The mitoinhibitory effect of OA was seen even in the presence of a strong mitogen such as epidermal growth factor (EGF).Cited by: This question was explored using resistance to the mitoinhibitory effects of orotic acid, a liver tumor promoter.

Accordingly, male Fischer rats were initiated with diethylnitrosamine (DENA) and later exposed to the resistant hepatocyte (RH) model of liver tumor promotion or to no further by: 2. In an attempt to examine this hypothesis, the present study was designed to determine (i) whether OA inhibits DNA synthesis in Studies on the mitoinhibitory effects of orotic acid on normal rat liver and hepatic nodules book hepatocytes in vivo, and (ii) whether hepatocytes from hepatic foci/nodules are relatively resistant to the mito-inhibitory effects of OA.

The results of this study indicate that OA given i.p. as a tablet of Cited by:   The results indicated that, in contrast to hepatocytes in normal or surrounding non-nodular liver, a subpopulation of hepatocyte foci/nodules appear to be relatively resistant to the mito-inhibitory effects of OA.

These findings support the hypothesis that differential mito-inhibition is a possible component in the promoting effect of by:   We have reported previously that orotic acid (OA), a precursor for pyrimidine nucleotide biosynthesis, is able to promote carcinogenic process in both liver and duodenum of rats.

The present study investigates the possible role of mitoinhibitory effects of OA as being responsible for its promotional effects. Male Fischer rats were given a semisynthetic basal diet (BD) or a diet Cited by: 7.

Influence of orotic acid on multistage hepatocarcinogenesis in the rat: resistance of hepatocytes from nodules to the mitoinhibitory effects of orotic acid.

Manjeshwar S, Laconi E, Rao PM, Rajalakshmi S, Sarma DS. Proc. Soc. Exp. Biol. Med., (1), 01 Jan Cited by: 2 articles | PMID: Similar patterns of results were obtained when the resistance of the foci to the mitoinhibitory effects of orotic acid, a liver tumor promoter and an inhibitor of DNA synthesis in normal.

This study was designed to determine whether hepatocytes from hepatic nodules are resistant to the mitoinhibitory effects of orotic acid. Hepatic nodules were initiated in Fischer male rats. Studies on liver tumor promotion in the rat by orotic acid: dose and minimum exposure time required for dietary orotic acid to promote hepatocarcinogenesis In vitro and in vivo response of hepatocytes from hepatic nodules to the mitoinhibitory effects of phenobarbital.

acid, imidazole, aminopterin, and folic acid have little or no effect. The properties of the mammalian phytanic acid-cr- oxidizing enzyme are discussed and compared with those of straight chain fatty acid-a-oxidizing systems in plants and animals.

l’hytanic acid (3,i, 11, hylhexadecanoic acid) was. Nonetheless, promotion by orotic acid is elegant in that by selecting the initiating carcinogen both cancer in the liver 5,6 as well as intestine 7 can be achieved. Being an intermediate in the de novo biosynthesis of pyrimidine nucleotides, orotic acid is rapidly metabolized by the liver to uridine nucleotides, which on accumulation creates an.

Orotic acid, nucleotide-pool imbalance, and liver-tumor promotion: a possible mechanism for the mitoinhibitory effects of orotic acid in isolated rat hepatocytes May Cancer Research 52(7. Background: Orotic acid (OA) is able to inhibit hepatocyte proliferation in vivo induced by 2 3 partial hepatectomy.

The present studies were aimed at establishing: (i) whether OA also inhibits hepatocyte proliferation induced by a direct mitogen and, if so (ii) whether the stimulus provided by the mitogen is still expressed following transient inhibition by OA.

In the present study, sequential histopathological changes during hepatocarcinogenesis promoted by orotic acid were examined. Male Fischer rats were given 1,2-dimethylhydrazine 2HCl ( mg/kg, i.p.) 18 h after 2 3 partial hepatectomy.

After 1 week of recovery, they were divided into 2 groups; group 1 was continued on a semisynthetic basal diet while the group 2 received the basal diet. Evidence for a possible homeostatic role of apoptosis comes from the finding of this type of cell death in very early hepatic preneoplastic lesions 4 induced by three different “initiation-promotion” protocols: the orotic acid model (OA), the resistant hepatocyte model (RH), and the choline deficient model (CD).

In this study it was shown. However, our earlier studies indicated that PB inhibited DNA synthesis in vitro in hepatocytes isolated from both surrounding non-nodular liver and hepatic nodules promoted by orotic acid (OA). Since nodules generated by one promoter need not necessarily be resistant to another promoter, the present study was undertaken to determine whether.

A. Sheikh, A. Yusuf, E. Laconi, P.M. Rao, S. Rajalakshmi, D.S.R. SarmaEffect of orotic acid on in vivo DNA synthesis in hepatocytes of normal rat liver and in hepatic foci/nodules Carcinogenesis (). Based on these obser- vations, it is likely that MG is selectively mitoinhibitory to surrounding normal hepatocytes and so the foci induced by DEN could be resistant to the cytotoxic effect of MG, thereby facilitating the progression of altered hepatocytes to form hepatic nodules and liver.

present study was to analyze the effects of three antioxidants on hepatic mitochondrial function and antioxidant status. Isolated rat liver mitochondria were incubated with vitamin C, resveratrol and lipoic acid.

The activity of antioxidant enzymes (manganese superoxide dismutase and. Mitoinhibitory effects have previously been demonstrated in vitro for orotic acid in isolated nodules, even though higher concentrations were used in those studies (Manjeshwar et al., ; Seikh, ).

Ethionine and dioxan also gave significantly different effects in the two cell types. Studies on the effect of dietary orotic acid on mouse liver carcinogenesis induced by diethylnitrosamine.

Effect of orotic acid on in vivo DNA synthesis in hepatocytes of normal rat liver and in hepatic foci/nodules. CarcinogenesisResistance of hepatocytes from nodules to the mito-inhibitory effects of orotic acid. BAHR GF, ZEITLER E. Study of mitochondria in rat liver. Quantitative electron microscopy.

J Cell Biol. Dec; – [PMC free article] []Barsano CP, Degroot LJ, Getz GS. The effect of thyroid hormone on in vitro rat liver mitochondrial RNA synthesis. Possible Mechanism of Orotic Acid Induced Liver Tumor Promotion in the Rat.

Pages Expression of a Novel N-Acetylglucosaminyltransferase in Rat Hepatic Nodules. Pages Regulation of S-Adenosyl-L-Methionine Decarboxylase in Normal and Regenerating Rat Liver by Adenosine-Containing Molecules.

Pages Hepatic steatosis is associated with mitochondrial oxidative alterations. This study aimed to characterize in a choline‐deficient model of rat fatty liver whether this oxidative imbalance is related to an impairment of the capacity of ATP synthesis both under fed conditions and after starvation, which may sensitize mitochondria to oxidative injury.

Orotic Acid Orotate Phosphoribosyltransferase: The enzyme catalyzing the formation of orotidine-5'-phosphoric acid (orotidylic acid) from orotic acid and 5-phosphoribosylpyrophosphate in the course of pyrimidine nucleotide Orotidine-5'-Phosphate Decarboxylase: Orotidine-5'-phosphate zes the decarboxylation of orotidylic acid to yield uridylic.

Percent labeling index of hepatocytes exposed to a mitoinhibitory dose of 2-AAF (5 mg/kg) in foci/nodules and surrounding non-nodular liver in animals initiated with a single necrogenic dose of DENA ( mg/kg) and exposed to no further treatment (A) or to a complete RH protocol of liver tumor promotion (B).Every focus/nodule in the section and 30 random fields in the surrounding non-nodular.

To the best of our knowledge, this is the first study concerning the effect of boric acid (BA) administration on fetal alcohol syndrome (FAS).

In this study, the aim was to investigate prenatal alcohol-induced oxidative stress on the cerebral cortex of newborn rat pups and assess the protective and beneficial effects of BA supplementation on rats with FAS.

Intact mitochondria, isolated from regenerating rat liver days after partial hepatectomy, are times more active in amino acid incorporation than mitochondria from control livers.

Liver mitochondria from sham-operated animals showed normal amounts of incorporation. Hepatic steatosis is associated with mitochondrial oxidative alterations. This study aimed to characterize in a choline-deficient model of rat fatty liver whether this oxidative imbalance is related to an impairment of the capacity of ATP synthesis both under fed conditions and after starvation, which may sensitize mitochondria to oxidative injury.

Isolation of rat liver mitochondria. Animals were humanely treated using protocols approved by the Institutional Animal Use and Care Committee. Liver mitochondria from overnight-fasted male Sprague–Dawley rats (– g) were isolated as described previously [].Briefly, livers were excized and minced in buffer A [ mM sucrose, mM EGTA and 2 mM K +-Hepes buffer (pH.

This study was designed to determine the possible mechanism by which orotic acid exerts its mitoinhibitory effect on rat hepatocytes in primary culture. Resistance of hepatic nodules to orotic acid-induced accumulation of uridine nucleotides.

The combination of elevated urinary orotic acid and plasma glutamine with normal citrulline. Abstract. Cancer induction by the non-genotoxic mycotoxin, fumonisin B 1, has been investigated by studying the mechanisms involved during cancer initiation and promotion in rat initiation is effected through a toxic-proliferative response while the inhibitory effect on hepatocyte cell proliferation appears to be a key aspect determining cancer promotion.

Effect of orotic acid on in vivo DNA synthesis in hepatocytes of normal rat liver and in hepatic foci/nodules. Sheikh A; Yusuf A; Laconi E; Rao PM; Rajalakshmi S; Sarma DS. CARCINOGENESIS: Influence of orotic acid on multistage hepatocarcinogenesis in the rat: resistance of hepatocytes from nodules to the mitoinhibitory effects of orotic.

Thus, the balance of Bcl-2 proteins in young rat liver mitochondria would favor bile acid induction of the MPT and cytochrome c release, which was in contrast to the observed MPT resistance in the. Weigh the liver, beaker and solution to obtain the actual liver weight and then carefully decant the bloody solution.

Continue to wash ( times), chop and decant until clear of the blood. Use solution B for the last two washes. Transfer the chopped liver (approx 1 mm cube in size) to a loose-fitting. Comparative Study on the Effect of Different Treatment Schedules on Some Carbohydrate Metabolizing Enzyme Activities in Rats During Hepatocarcinogenesis.- Expression of a Novel N-Acetylglucosaminyltransferase in Rat Hepatic Nodules.- Cytosolic and Plasmamembranes Enzymatic Activities During Diethylnitrosamine-Induced Carcinogenesis in Rat Liver Studies of mitochondrial oxidative metabolism revealed a consistent and progressive decrease in state 3 (ADP‐stimulated) respiration and in respiratory control ratios at hepatic iron concentrations above 1, μg per gm for all three substrates studied, glutamate, β‐hydroxybutyrate and succinate.

in vitro the effects on both disrupted and uninhibited cellular respiration by various substrates and metabolic poisons at different steps in the ETS process.

More specifically, this study questioned where these substrates and poisons affected the transport chain. We isolated mitochondria from fresh rat liver using differential centrifugation. ritin) ( mg Fe per ml) was added to whole liver homogenates (n = 9) in amounts equivalent to an hepatic iron concentration of 2, pg Fe per gm liver.

Hemosid- erin was prepared from iron overloaded rat liver using the method of McCay and Fineberg (18) and was added to the postnuclear supernatants from normal liver ho. We examined the effects of chronic dietary iron overload on hepatic mitochondrial oxidative metabolism.

Experimental iron overload was produced by feeding rats a chow diet supplemented with carbonyl iron over a 7‐week period. Biochemical and histologic evaluations of liver tissue confirmed moderate degrees of hepatic parenchymal iron overload. Non-alcoholic fatty liver disease has been proposed as a pathogenetic process that could affect multiple organs.

The first effect is the ac-cumulation of hepatic fat, which eventually leads to insulin resistance (IR), followed by the secondary effects comprising mitochondrial dys-function, oxidative stress, and adipocytokine imbalance.

Therefore.Impairment of liver mitochondrial β-oxidation is an important mechanism of drug-induced liver injury. Four inhibitors of fatty acid oxidation were compared in short-term rat in vivo studies in which the rats were administered one or four doses.

The hepatocellular vacuolation represented ultrastructural mitochondrial changes.Mack P, Tranberg K-G, Stenram U, Jeppsson B, Widlus D, Bengmark S. RNA labelling with 3H-orotic acid and 3H-fluorouracil of rat liver tumour following transient hepatic arterial ischaemia.

Eur J Surg Oncol ;

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