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Biomedical subjects

C C Yan

Publications and source records attributed to C C Yan.

31 records · Page 2Linked to original sources
PubMed1995

The effect of the pyrrolizidine alkaloids, monocrotaline and trichodesmine, on tissue pyrrole binding and glutathione metabolism in the rat.

One day after in vivo administration of equitoxic doses of the hepatotoxic and pneumotoxic pyrrolizidine alkaloid, monocrotaline (65 mg/kg, i. p.) or the related hepatotoxic and neurotoxic alkaloid trichodesmine (15 mg/kg, i. p.) hepatic GSH levels are increased by more than 50%. These doses of alkaloids represent 60% of the LD50 values. Accompanying these changes in GSH levels is an increase in the overall rate of GSH synthesis in supernatants of alkaloid-exposed livers. The ability of the rat to metabolize the two alkaloids was shown by the appearance of tissuebound pyrrolic metabolites of pyrrolizidines in various organs. The levels of these metabolites appear to correlate with organ toxicity. For the hepatic and pneumotoxic alkaloid, monocrotaline, higher levels are found in liver (17 nmoles/g tissue) and lung (10 nmoles/g) than for trichodesmine (7 nmoles/g and 8 nmoles/g, respectively). For the neurotoxic alkaloid, trichodesmine, higher levels are found in brain (3.8 nmoles/g tissue) than for monocrotaline (1.7 nmoles/g tissue).

Alkaloids↗
PubMed1994

Quantitation of the hepatic release of metabolites of the pyrrolizidine alkaloid, monocrotaline.

Pyrrolizidine alkaloids such as monocrotaline are bioactivated in the liver to pneumotoxins that cause pulmonary arterial hypertension and right ventricular hypertrophy. The release of the highly reactive, alkylating pyrrole, dehydromonocrotaline, from the isolated rat liver perfused with monocrotaline has now been demonstrated and quantified, using thiopropyl Sepharose resin as a trapping agent. The isolated liver extracted 55% of the alkaloid over the course of a 1-hr perfusion with 0.5 mM monocrotaline. Of the total monocrotaline perfused, 0.4% was excreted into bile and 7.6% was detectable as pyrrolic metabolites. Of these metabolites, 156 nmol/g liver appeared in the bile as glutathionyldehydroretronecine, with the average concentration in bile being 3.53 mM. The perfusion medium at the end of the perfusion contained 113 nmol/g liver of the two pyrroles, dehydroretronecine and glutathionyldehydroretronecine. Remaining in the liver was 56 nmol/g of tissue-bound pyrroles. Over the course of a 1-hr perfusion, 88 nmol/g liver of dehydromonocrotaline was released into the perfusate, as determined by trapping with thiopropyl Sepharose, a resin that reacts only with alkylating pyrroles. This establishes that dehydromonocrotaline is released on perfusing the isolated liver with monocrotaline. The amount released under these conditions is equivalent to 1.08 +/- 0.06 mg/kg body weight, which can be compared to the intravenous dose of 4.85 mg/kg body weight of dehydromonocrotaline found by others to be a pneumotoxic dose.

Animals↗
PubMed1993

Effects of cholesterol uptake from high-density lipoprotein on bile secretion and 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in perfused rat liver.

Small aliquots of rat high-density lipoproteins (HDL) (388 +/- 67 nmol lipoprotein cholesterol) were labeled with [14C]cholesterol and administered as a bolus to perfused rat livers. Bile and perfusate samples were collected for 2 hours at 30-minute intervals. After perfusion, both the microsomes and lipid extracts were prepared from the livers. Lipid composition was examined in both liver and microsomes, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity was evaluated in microsomes. Basal values of bile flow, lipid composition, and enzyme activity were evaluated using livers in which perfusion was discontinued before injecting the lipoprotein. In some experiments, the effect of perfusion per se was assessed by infusing saline instead of lipoprotein. After 10 minutes of lipoprotein perfusion, 50% of cholesterol administered was taken up by the perfused liver. During infusion, transient but significant increases in both bile flow and bile steroid secretion were observed. Cholesterol administration, even if rapid, represented less than 0.4% of total liver cholesterol content. However, this was enough to significantly increase the cholesterol to phospholipid (CH/PL) molar ratio in liver microsomes and at the same time decrease HMG-CoA reductase activity. In conclusion, the main response of the perfused liver to HDL cholesterol infusion is a reduced activity of the rate-limiting enzyme in cholesterol biosynthesis, due to the shift in the microsomal CH/PL molar ratio. A small proportion of the infused cholesterol enters bile as cholesterol and bile salts.

Animals↗
PubMed1993

Effect of taurine levels on liver lipid metabolism: an in vivo study in the rat.

Previous studies using guinea pigs and cats have shown that liver lipid composition is affected by intrahepatic taurine levels. The purpose of the present study was to determine whether this sulfonated amino acid could also affect lipid metabolism in the rat, an animal capable of synthesizing substantial amounts of taurine and used extensively in studies on lipid metabolism. Wide variations in the hepatic taurine content were induced by administering either 1% taurine or 1% guanidinoethane sulfonate in the drinking water for 2 weeks. These treatments increased and decreased taurine liver content, respectively, but did not affect either food or water intakes, or growth rates. The plasma concentrations of the major lipid classes in treated animals did not show any significant alteration in comparison to control animals, except for nonesterified fatty acid levels that were significantly lowered by guanidinoethane sulfonate administration. Taurine supplementation did cause a significant decrease in total hepatic lipid content that was attributable to the reduction of free and esterified cholesterol, triglyceride, and phosphatidylethanolamine hepatic concentrations. This same treatment slightly increased both bile flow and secretion of taurine-conjugated primary bile salts. In particular, the proportion of tauro-beta-muricholate significantly increased, whereas that of taurodeoxycholate greatly decreased. The administration of guanidinoethane sulfonate reduced both the bile flow and the secretion of taurine-conjugated bile salts and caused a significant alteration in the ratio between glycine- and taurine-conjugated bile salts. This did not occur after the treatment with taurine. Interestingly, we observed an inverse correlation between hepatic taurine levels and the proportion of either cholesteryl ester in hepatic lipids or taurochenodeoxycholate in biliary bile salts. These facts suggest that taurine hepatic levels influence mostly hepatic steroid metabolism, but they also affect the metabolism of other lipid classes.

Analysis of Variance↗
PubMed1993

Characterization of lipoprotein fractions isolated from plasma of male Wistar rats by gradient ultracentrifugation.

Both Wistar and Sprague-Dawley rat strains have been used for experimental studies on lipoprotein metabolism, although the lipoprotein characteristics of the former strain are less well known than those of the latter. We have defined more precise conditions for separating by density gradient ultracentrifugation the different lipoprotein classes from plasma of young male Wistar rats. Present results confirm that Wistar rats, like other rat strains, have negligible amounts of low density lipoproteins and levels of very low density lipoproteins much lower than high density lipoproteins. The differences between rat strains appeared in the profile of lipoprotein denser than 1.08 g/ml. In fact, we showed Wistar rats have considerable amounts of high density lipoprotein-3 subfraction with a density range between 1.17 and 1.21 g/ml, a mean diameter of 4.9 nm, and a low cholesterol content. In analogy with the Sprague-Dawley strain, Wistar rats had a small proportion of high density lipoprotein-1 subfraction (about 17% of total lipoproteins) and, at variance, in Wistar rats, we did not observe the presence of the so-called very high density lipoprotein fraction described previously in the Sprague-Dawley strain.

Animals↗
PubMed1992

Effect of HDL1 infusion on biliary secretion in perfused rat liver.

The effects of HDL1 lipoprotein infusion on biliary lipid secretion were studied in the in vitro model of rat perfused liver. A strong increase in bile flow was observed during and after lipoprotein infusion. This caused a significant rise in cholesterol, phospholipid and bile salt secretions. However, only the percentage of cholesterol increased with respect to the other bile lipids. The changes observed in the cholesterol/phospholipid molar ratio values of liver membrane subfractions (i.e., liver plasma membrane, mitochondria plus lysosomes and microsomes) isolated from the perfused rat liver after HDL1 administration were not significant.

Animals↗
PubMed1975

Typhoid polymyositis.

Four patients with typhoid polymyositis, 3 of whom were members of one family, are described. There was clinical, biochemical and histological evidence of severe muscle involvement which reversed on treatment with Chloromycetin. Muscle involvement in typhoid fever is a recognised pathological entity, but a clinical syndrome involving muscle has not previously been described.

Adolescent↗