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Biomedical subjects

M Bhargava

Publications and source records attributed to M Bhargava.

At least 91 records · Page 5Linked to original sources
PubMed1984

Chronic experimental iron losses in rats not leading to overt iron deficiency: a model for the regulation of the whole-body iron balance in an iron-replete condition.

Intestinal iron absorption studies, which include investigation of iron deficiency, increased erythropoiesis, low iron diet and acute bleeding, have been done, but none have reported the regulation of the balance of an iron-replete individual. We bled rats at regular time intervals, such that the experimentally induced iron losses were compensated by iron from storage and nutritional procurement without the onset of anemia. During these experimental periods the hemoglobin and plasma iron concentrations were determined along with repeated histochemical gradings of the bone marrow iron. We determined the intestinal iron absorption at regular intervals after having established its relation to the intragastric ferrous iron dose. The results obtained show that regular bleedings of 15-20% of the total blood volume every 10 days or twice a week, respectively, are compensated completely by storage and nutritional iron procurement without the onset of anemia. The intestinal iron absorption is increased 4 hours after an acute bleeding and was found high during the period that the animals were bled every 10 days. Significant changes of the plasma iron concentration, mostly within the "normal range" are invariably associated with experimental changes in bleeding regimes. The observed increases of the intestinal absorption of a ferrous iron test dose and decreases of the plasma iron concentrations that precede the depletion of the histochemically graded bone marrow iron are interpreted by a modification of a reported model, in which the process of iron release into the plasma from the reticuloendothelial system and the gut mucosa is linked closely to the actual plasma iron concentration.

Animals↗
PubMed1981

Binding of 3'-methyl-N,N-dimethyl-4-aminoazobenzene metabolites to rat liver cytosol proteins and ligandin subunits.

Twenty min after i.p. administration of 3'-[14C]methyl-N,N-dimethyl-4-aminoazobenzene in corn oil to rats, 0.73% of administered radioactivity was present in the liver. Only 0.45% of radioactivity present in liver was recovered in the nuclear fraction, whereas 25% was present in the cytosol fraction. Twenty-seven % of cytosolic radioactivity was trichloroacetic acid precipitable, and 2% was immunoprecipitable with monospecific anti-rat liver ligandin immunoglobulin G. After 3 hr of administration, 3.2% of administered radioactivity was present in the liver, 40% of which was in the cytosol. Although 59% of radioactivity present in liver cytosol was trichloroacetic acid precipitable as compared to 27% at 20 min, the radioactivity precipitated by anti-ligandin immunoglobulin G was still 2%. When liver cytosol obtained from rats after 20 min of 3'-[14C]methyl-N,N-dimethyl-4-aminoazobenzene administration was fractionated on a Sephadex G-75 column, three peaks of radioactivity were observed. When cytosol was subjected to sodium dodecyl sulfate gel electrophoresis and fluorography, radioactivity was mainly associated with 5 proteins with molecular weights of 88,000, 47,000, 41,000, 31,000, and 22,000. When the immunoprecipitate obtained from cytosol with anti-ligandin immunoglobulin G was subjected to sodium dodecyl sulfate gel electrophoresis and fluorography, radioactivity was exclusively associated with the subunit of ligandin with a molecular weight of 22,000. Approximately 90% of the radioactivity in the immunoprecipitate was covalently associated with this subunit. These studies reveal that 3'-methyl-N,N-dimethyl-4-aminoazobenzene or its metabolites are selectively bound to the subunit of ligandin with a molecular weight of 22,000 and four other cytosol proteins in vivo.

Animals↗
PubMed1980

Ligandin: an adventure in liverland.

Ligandin is an abundant soluble protein which has a t 1/2 of 2--3 days, is induced by many drugs and chemicals, and is stabilized in the absence of thyroid hormone. The protein is strategically concentrated in cells associated with transport and detoxification of many endogenous ligands, such as bilirubin, and exogenous ligands, such as drugs and chemicals. The protein is a dimer in rat liver. Whether the dimer is a primary gene product or at least two genes are involved is not known. The protein has broad, low affinity catalytic activity as a GSH-S-transferase for many ligands having electrophilic groups and hydrophobic domains. It catalyzes formation of GSH conjugates, non-covalently binds some ligands prior to their biotransformation or excretion in bile, and covalently binds other ligands, such as activated carcinogens. Recent studies include the possible role of ligandin in chemical carcinogenesis, diagnosis of inflammatory and neoplastic disease of the liver and kidney, and participation in intracellular transport. Although some of the roles that have been outlined are speculative, any single function is important. The GSH-S-transferases are primitive enzymes and non-specific binding proteins but "it is precisely their simplistic design that allows such protean serviceability". Ligandin illustrates a group of hepatic disposal mechanisms which involve bulk transport of ligands. Although specific uptake and transport mechanisms have been described for several hormones which enter the hepatocyte in small quantities and regulate intermediary metabolism and, possibly, cell maturation, bulk transport of ligands into, through and out of the liver involves mechanisms which accomodate many metabolites, drugs and chemicals of diverse structure. The liver is bathed in sewage which contains what we ingest or are injected with and potentially toxic products of intestinal microorganisms. The chemical formulas of the many substances which are metabolized by the liver provide a horror show of potentially reactive and toxic metabolites, mutagens and carcinogens. Despite this alimentary "Love Canal", we and our livers do remarkably well. These hepatic disposal mechanisms, as exemplified by ligandin, evolved in ancient times. They are present, albeit sluggishly, in insects and ancient elasmobranchs. Hepatic uptake and removal mechanisms of high capacity, modest affinity and broad substrate range permit us to live in what has probably always been a threatening world.

Animals↗
PubMed1979

Ligandin subunits and hepatocellular carcinoma in man and rat.

Covalent binding of activated azo dye and methyl cholanthrene carcinogens preferentially occurs to subunit B of ligandin. This subunit contains 7 of ligandin's 9 cysteine residues which, according to Ketterer et al, are the site of covalent carcinogen binding. Subunit B appears to be cytoplasmic and intranuclear. We postulate that binding of activated carcinogens to subunit B may facilitate their transfer from cytoplasm to nucleus. Rat and human primary liver cell cancers often contain ligandin which is released into the circulation. In patients at risk for, or suspected of having primary liver cell cancer, increased serum ligandin concentrations may have diagnostic value.

Animals↗