Inhibition of aldose reductase and xylose-induced lens opacity by puerariafuran from the roots of Pueraria lobata.

High sugar levels found in diabetic cataract cause the opacification of lenses by osmotic changes induced via the aldose reductase (AR)-mediated polyol pathway. In this study, puerariafuran, a 2-arylbenzofuran from Pueraria lobata, investigated the inhibitory effects upon AR, antioxidant contents and enzyme activities in the lens. The effect of puerariafuran on xylose-induced lens opacity was also examined. Puerariafuran showed potential inhibitory activity with an IC50 value of 22.34 microM against rat lens AR. The xylose-induced opacity of lenses was significantly improved when treated with puerariafuran. Xylose exposure of rat lenses significantly decreased the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, superoxide dismutase (SOD), and catalase (CAT) activity and treatment with puerariafuran significantly increased these factors. These results suggest that puerariafuran may provide a potential therapeutic approach for prevention of diabetic complications, such as cataracts.

Two different pathways for D-xylose metabolism and the effect of xylose concentration on the yield coefficient of L-lactate in mixed-acid fermentation by the lactic acid bacterium Lactococcus lactis IO-1.

In lactic acid bacteria, pentoses are metabolized via the phosphoketolase pathway, which catalyzes the cleavage of D-xylulose-5-phosphate to equimolar amounts of glyceraldehyde 3-phosphate and acetylphosphate. Hence the yield coefficient of lactate from pentose does not exceed 1.0 mol/mol, while that of Lactococcus lactis IO-1(JCM7638) at high D-xylose concentrations often exceeds the theoretical value. This suggests that, in addition to the phosphoketolase pathway, L. lactisIO-1 may possess another metabolic pathway that produces only lactic acid from xylose. In the present study, the metabolism of xylose in L. lactisIO-1 was deduced from the product formation and enzyme activities of L. lactisIO-1 in batch culture and continuous culture. During cultivation with xylose concentrations above ca. 50 g/l, the yield coefficient of L-lactate exceeded 1.0 mol/mol while those of acetate, formate and ethanol were very low. At xylose concentrations less than 5 g/l, acetate, formate and ethanol were produced with yield coefficients of about 1.0 mol/mol, while L-lactate was scarcely produced. In cells grown at high xylose concentrations, a marked decrease in the specific activities of phosphoketolase and pyruvate formate lyase (PFL), and an increase in those of transketolase and transaldolase were observed. These results indicate that in L. lactisIO-1 xylose may be catabolized by two different pathways, the phosphoketolase pathway yielding acetate, formate and ethanol, and the pentose phosphate (PP)/glycolytic pathway which converts xylose to L-lactate only. Furthermore, it was deduced that the change in the xylose concentration in the culture medium shifts xylulose 5-phosphate metabolism between the phosphoketolase pathway and the PP/glycolytic pathway in L. lactisIO-1, and pyruvate metabolism between cleavage to acetyl-CoA and formic acid by PFL and the reduction to L-lactate by lactate dehydrogenase.

Na(+)-dependent transport of D-xylose by bovine intestinal brush border membrane vesicles (BBMV) is inhibited by various pentoses and hexoses.

To detect whether pentoses and hexoses occurring in rumen bacteria or in hemicellulose ingested with feed and partly released in the small intestine have an affinity for the Na(+)-dependent glucose transporter of the bovine intestinal brush border membrane (BBM), we investigated whether these monosaccharides inhibit Na(+)-dependent transport of 14C-labelled D-xylose across the BBM using brush border membrane vesicles (BBMV) isolated from the mid-jejunum of cows. We used D-xylose as the transport substrate, because it has a low affinity for the Na(+)-dependent glucose transporter and thus its uptake into BBMV is more efficiently competitively inhibited by other sugars than that of D-glucose. D-Ribose, D-mannose and L-rhamnose occurring in rumen bacteria significantly inhibited Na(+)-dependent uptake of D-xylose into BBMV, but their inhibitory effect was less than that of D-glucose, D-xylose and phlorizin. This also applied to L-arabinose (and D-arabinose), which is, like D-xylose and D-galactose, a constituent of hemicellulose, and to 2-deoxy-D-glucose. Of all monosaccharides tested, only D-fructose did not affect Na(+)-dependent D-xylose transport. It is concluded that some pentoses and hexoses occurring in rumen bacteria (D-ribose, D-mannose and L-rhamnose) or hemicellulose (L-arabinose and D-xylose) have a low affinity for the Na(+)-dependent glucose transporter of the bovine BBM and may therefore be absorbed from the jejunum when released in the small intestine.

D-xylose catabolism in Bacteroides xylanolyticus X5-1.

The xylose metabolism of Bacteroides xylanolyticus X5-1 was studied by determining specific enzyme activities in cell free extracts, by following 13C-label distribution patterns in growing cultures and by mass balance calculations. Enzyme activities of the pentose phosphate pathway and the Embden-Meyerhof-Parnas pathway were sufficiently high to account for in vivo xylose fermentation to pyruvate via a combination of these two pathways. Pyruvate was mainly oxidized to acetyl-CoA, CO2 and a reduced cofactor (ferredoxin). Part of the pyruvate was converted to acetyl-CoA and formate by means of a pyruvate-formate lyase. Acetyl-CoA was either converted to acetate by a combined action of phosphotransacetylase and acetate kinase or reduced to ethanol by an acetaldehyde dehydrogenase and an ethanol dehydrogenase. The latter two enzymes displayed both a NADH- and a NADPH-linked activity. Cofactor regeneration proceeded via a reduction of intermediates of the metabolism (i.e. acetyl-CoA and acetaldehyde) and via proton reduction. According to the deduced pathway about 2.5 mol ATP are generated per mol of xylose degraded.

[Transport of monosaccharides in model systems: inhibition of sugar transport in frog muscle fibers, treated with glutaraldehyde]. / Transport monosakharidov v modelnykh sistemakh: ingibirovanie transporta sakharov v myshechnykh voloknakh liagushki, obrabotannykh glutaral'degidom.

The entry of D-xylose, a permeable non-metabolizing glucose analog, in the frog muscle fibers was examined. The sugar transport system activity was established in the frog muscle fibers treated by 0.3% glutaraldehyde. The basal transport as well as insulin activated D-xylose transport was seen preserved. Sugar transport inhibitors, phlorizin, phloretin and cytochalasine B reduce the rate of D-xylose transport in this "glutar model" of a muscle fiber. A long treatment by glutaraldehyde (3.5 hours at 4 degrees C, and 1 hour at 20 degrees C) leads to a 40% decline in the entry rate of D-xylose.

Inhibition of digoxin absorption by neomycin.

The effect of the administration of the antibiotic neomycin sulfate on the absorption of digoxin was assessed in crossover studies in normal human volunteers. Doses of neomycin (1 and 3 g) markedly depressed serum digoxin concentrations, the areas under the serum concentration-time curves, and cumulative 6-day urinary digoxin excretion after the oral ingestion of 0.5 mg of the cardiac glycoside in tablet form. Neomycin also prolonged the mean time at which peak serum digoxin levels were attained by 1.7 to 3 hr. The inhibition of digoxin absorption was also seen: (1) when the antibiotic was given 3 or 6 hr before the cardiac glycoside, (2) with digoxin tablets of varying dissolution rate, (3) when digoxin or neomycin solutions were used instead of tablets, and (4) in a patient who had had a total gastrectomy. When neomycin was administered with maintenance doses of digoxin, steady state serum digoxin concentrations were significantly reduced. When neomycin was given after a 9-day period of digitalization, the terminal serum digoxin half-life was not significantly shortened. Single doses of neomycin did not interfere with the extent of absorption of d-xylose. In vitro, neomycin did not affect the movement of digoxin across dialysis membranes, nor did it precipitate digoxin out of human bile or intestinal fluid. Neomycin thus clearly depresses the rate and extent of digoxin absorption in man. The mechanism of this effect remains to be established.