Lipotrope-deficient Diet Research Articles

Processing of IgA Aggregates in a Rat Model of Chronic Liver Disease

Heavy alcohol intake and/or lipotrope-deficient diet induced hepatocellular injury and mesangial deposition of IgA and often IgG in Lewis rats. The experimental animals showing more severe urinary abnormalities and histologic damage in the glomeruli had increased levels of IgA antibodies to dietary antigens and altered intestinal permeability. Based on human studies, the prolonged circulation of IgA-containing complexes associated with the liver disease could be envisaged as important for the development of mesangial IgA deposits. In order to verify this hypothesis, four groups (G) of Lewis rats were studied: G1 received thrice a week an intragastric infusion of 1.5 ml/100 g body wt of whiskey; G2 rats were nourished with lipotrope-deficient diet; G3 rats were given both whiskey and LD diet; G4 rats were nourished with regular chow. After 12 weeks, heat-aggregated rat monomeric IgA was labeled with123I and intravenously injected. Three control subgroups of rats, one given whiskey, one nourished with LD diet, and one with regular chow, were injected with radiolabeled heat-aggregated rat IgG. A large field-of-view digital gamma camera, equipped with an ultra-high-resolution collimator and interfaced to a dedicated computer, was used to analyze tracer kinetics and fate. The liver was the main organ involved in clearance of both test probes. The hepatic mean transit (MTT) was 114 ± 11 min in G1 (proteinuria of 6.9 ± 1.41 mg/day and hematuria +/++), 221 ± 19 min in G2 (proteinuria 9.1 ± 0.64 mg/day and hematuria ++/+++), and 230 ± 15 min in G3 (proteinuria 9.5 ± 0.58 mg/day and hematuria ++/+++). In each case MTT value was found to be significantly prolonged compared to G4 (85 ± 4 min). The multiple regression analysis showed that MTT values, proteinuria, and hematuria were significantly correlated (P< 0.01). Controls had trace amount proteinuria (0.82 ± 0.17 mg/day, significantly lower than for each study group,P< 0.03) and undetectable hematuria. Similar results were obtained in control rats injected with aggregated IgG; i.e., MTT values were more prolonged in rats given whiskey or LD diet than normally nourished rats (P< 0.01). The lipotrope-deficient diet and the chronic alcohol abuse per se seem to lead to critical changes in hepatic uptake and catabolism of both an IgA and an IgG aggregate, which could account in turn for the reported appearance of renal immunoglobulin deposits in this experimental model. Due to the comparable delay in removal of IgA and IgG probes in equally nourished animals, additional factors are likely to be involved in the prominent deposition of IgA.

16,16-dimethyl prostaglandin E2 delays collagen formation in nutritional injury in rat liver†

Chronic nutritional injury was induced in rats by a high-fat, lipotrope-deficient diet. The hepatoprotective effect of 16,16-dimethyl prostaglandin E2 on the deposition of collagen and fat was assessed by histological evaluation and measurement of hydroxyproline. Dose-response studies established that optimal protection was achieved by the twice daily administration of 16,16-dimethyl prostaglandin E2 at 100 micrograms per kg (subcutaneous) or 250 micrograms per kg (oral). 16,16-Dimethyl prostaglandin E2 and a crystalline analog [(p-acetamidobenzamido)phenyl ester of 16,16-dimethyl prostaglandin E2 significantly delayed both the deposition of collagen and the increase in hepatic hydroxyproline content. There was an excellent correlation between the histological assessment of collagen and the biochemical measurement of hydroxyproline. These data provide a rationale for the evaluation of prostaglandins in the treatment of human liver disease.

Altered tRNA methylation in rats and mice fed lipotrope-deficient diets.

A diet that is deficient in methionine, choline, folic acid and vitamin B12 has been found to induce alterations rapidly in liver tRNA methylation in male Fischer rats. In vitro assays indicated that activity of N2-guanine tRNA methyltransferase II (NMG2) was increased to 150% of controls levels in 1 week and 300% of control levels after 2 weeks or longer on this diet. Incompletely methylated tRNA was isolated from livers of these same animals, indicating that there was impairment of methylation in vivo. The effects on liver tRNA methylation of this methyl-deficient diet were thus seen to mimic those of the liver carcinogen, ethionine, which also causes production of hypomethylated tRNA and increased activity of NMG2. The effect of the same diet on liver tRNA methyltransferase activity of C57BL/6J and C3H/HeJ inbred mice were also studied. Intake of the lipotrope-deficient diet induced elevation in activity of liver N2-guanine tRNA methyltransferase II activity in C57BL/6J mice, similar to that seen in rats. In contrast, the methyl-deficient diet had very little effect on the same enzyme activity in C3H/HeJ animals.

Early Stages of Nodular Transformation of the B6C3F1 Mouse Liver Induced by Choline Deficiency

The B6C3F1 strain of mice is prone to develop liver nodules as animals grow older. This spontaneous tumor development is enhanced by dietary lipotrope deficiency. The present studies were performed to evaluate the liver of the B6C3F1 mice in early periods of lipotrope deficiency and before the nodules appear. Mice were fed high levels of dietary fat (cotton seed oil or beef fat) without choline or vitamin B12. The livers of these mice were compared with those of mice subjected to partial hepatectomy or dietary phenobarbital both of which enhance liver nodule formation. The ability of putative preneoplastic hepatocytes to exclude parenteral-administered iron was used to detect this eventual phenotype. A lipotrope-deficient condition was established which typically exhibited fatty liver and increased cell proliferation, the latter measured by autoradiography. In the time periods evaluated the lipotrope-devoid diets were not sufficient to induce nodular or putative preneoplastic lesions. An excessively high activity of p-nitroanisole-O-demethylase and a single small fatty nodule were obtained when phenobarbital was added to the lipotrope-deficient diet. Scattered eosinophilic hepatocytes were seen in every experimental group when the histologic slides were stained for iron pigments, but their biologic significance in the present experiments could not be established. Under the conditions of this study, the liver of the B6C3F1 strain of mouse exhibited only minor indications of future tumor development.

Effect of a marginally lipotrope-deficient diet on methylazoxymethanol acetate carcinogenesis.

The effect of a lipotrope-deficient diet on methylazoxymethanol acetate (MAM acetate) intestinal carcinogenesis was studied in 2 groups of ACI rats. For 10 weeks, weanling rats were fed a semisynthetic diet that was either high in fat and marginally deficient in the lipotropes (Group 1), or adequate for rats in all known respects (Group 2). Four weeks after the start of the experimental diets, the animals were given a weekly SC injection of MAM acetate, 25 mg/kg body weight, for a total of 5 times. Following the termination of the experimental diets, the animals were fed a basal diet until the end of the experiment (480 days). The tumor incidence in the jejunum-ileum and the number of tumors in the colon were significantly higher in Group 1 than in Group 2. These results suggest that a marginally lipotrope-deficient diet enhances MAM acetate carcinogenesis, probably in its early stage.

Effects of diet on conversion of aflatoxin B 1 to bacterial mutagen(s) by rats in vivo and by rat hepatic microsomes in vitro

A lipotrope-deficient, high-fat diet that enhances aflatoxin B 1 (AFB 1) hepatocarcinogenesis in rats influenced in two ways the conversion of AFB 1 to mutagens detectable in the Ames Salmonella mutagenesis test system. First, in the urine of rats fed the lipotrope-deficient diet and given a single dose of AFB 1, the proportion of mutagenic material that did not require activation by hepatic microsomes was higher than in the urine of rats fed an adequate diet. Second, hepatic microsomal preparations (S-9 fractions) from deficient animals showed significantly lower activity in the in vitro converstion of AFB 1 to mutagen(s) than did S-9 fractions from normal animals. The S-9 fractions from deficient animals actually suppressed the activity of normal S-9 fractions in a mixed mutagenesis assay. The inconsistency of the second finding with the enhanced sensitivity of deficient animals to AFB 1 carcinogenesis sugggests the need for some caution in using the in vitro mutagenesis tests for quantitative estimation of carcinogenic potency.

Liver disease and ammonia intoxication

The relation between ammonia intoxication and liver disease is not clear. Ammonia appears to be relatively non-toxic to normal individuals, whereas some patients with liver disease appear to be exquisitely...