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Biomedical subjects

E Bosisio

Publications and source records attributed to E Bosisio.

69 records · Page 4Linked to original sources
PubMedDate not supplied

Effect of natural and structurally modified bile acids on cholesterol metabolizing enzymes in rat liver microsomes. II.

The effect of ursodeoxycholic acid analogues bearing modifications at the side-chain moiety of the molecule was tested on cholesterol 7 alpha-hydroxylase and HMG-CoA reductase in rat liver microsomes. The compounds included 23 R,S mixture and the single isomers 23R and 23S of 23 methylursodeoxycholic acid (23-methyl UDCA), the isomeric mixture (cis + trans) of 3 alpha,7 beta-dihydroxy-20,22-methylen-5 beta-cholan-23-oic acid (norcypro-UDCA) and the corresponding single isomers. Each steroid was added to liver microsomes as the sodium salt, at concentrations ranging from 25 to 200 microM. Isomers 23R and 23S of 23-methyl-UDCA inhibited cholesterol 7 alpha-hydroxylase in a concentration-dependent manner. The inhibitory capacity was similar for the two isomers. The extent of inhibition of the analogues was greater than that of the parent compound UDCA. Shortening of the side-chain in norcypro-UDCA resulted in a partial loss of the inhibitory effect, as compared to cypro-UDCA (3 alpha,7 beta-dihydroxy-22,23-methylen-5 beta-cholan-24-oic acid). None of these bile acid derivatives affected the activity of the enzyme HMG-CoA reductase.

Animals↗
PubMedDate not supplied

The effect of etofibrate on cholesterol and bile acid metabolism in the hamster.

Hamsters were given etofibrate at a dose of 300 mg/kg body wt, by gavage for 5 days, while being fed a chow diet. After treatment, serum cholesterol levels were 27% lower compared to those of the control animals. A similar trend was observed for triglyceride levels. Hepatic lipid levels were unchanged by the treatment. HMG-CoA reductase and acylCoA cholesterol acyltransferase were decreased while cholesterol 7 alpha-hydroxylase was not significantly modified by etofibrate. A choleretic effect and an increase of cholesterol excretion into hepatic bile was observed in treated animals. Nevertheless, composition and cholesterol saturation index of gallbladder bile were similar in control and treated animals. With respect to controls, hepatic bile of treated hamsters contained a lesser amount of cholic and deoxycholic acid and a greater amount of ursodeoxycholic acid.

Animals↗
PubMedDate not supplied

Effect of the flavanolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes.

The effect of several flavanolignans (silicristin, silidianin, silybin and isosilybin) present in silymarin, the extract of Silybum marianum fruits, was tested on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. In microsomes lipid peroxidation was generated by ADP/Fe2+ and NADPH. All flavanolignans inhibited peroxidation in a concentration dependent manner. In hepatocytes lipid peroxidation was induced by ADP/Fe3+ complex and cell damage was evaluated as LDH activity released in the medium. The inhibition of the peroxidative process by flavanolignans was also evident in this model, even if with a potency order different from that found in microsomes. In contrast, the effect on LDH release was significant only for silybin and isosilybin, the other compounds being inactive on this parameter.

Animals↗
PubMedDate not supplied

Phytochemical characterization and radical scavenger activity of flavonoids from Helichrysum italicum G. Don (Compositae).

The glycosidic fraction of the flavonoids extracted from the flowering tops of the Helichrysum italicum G. Don was isolated, purified and characterized. This fraction was constituted by three compounds, which were assigned the structure of 4,2',4',6'-tetrahydroxychalcone-2'-glucoside, kaempferol-3-glucoside and naringenin-glycoside. Radical scavenger properties of the single glycosyl-flavonoids and of the in toto glycosidic fraction were tested with in vitro systems where different reactive oxygen species are generated (superoxide ions, hydroxyl radicals) and on lipid peroxidation induced by ADP/Fe2+ and NADPH or CCl4 in rat liver microsomes. The formation of reactive oxygen species was detected by cytochrome c reduction, salicylic acid hydroxylation and hyaluronic acid depolymerization. The action of the glycosidic fraction on the release of TXB2 and 12-HETE in human platelets, after collagen stimulation, was also evaluated. The glycosidic fraction inhibited in a dose dependent fashion lipid peroxidation in rat liver microsomes treated with ADP/Fe2+ or CCl4. This effect is due to the ability of flavonoids to scavenge free radicals at different stages of the process (superoxide ions, hydroxyl and lipid peroxide radicals). The single glycosyl-flavonoids exhibited a different scavenger activity, depending on the oxygen species and the chemical structure of the compounds. No effect of the fraction was observed on TXB2 and 12-HETE formation at 100 microns concentration.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMedDate not supplied

Metformin improves peripheral vascular flow in nonhyperlipidemic patients with arterial disease.

The clinical activity of metformin (N,N-dimethyl biguanide), a widely used antidiabetic agent, on arterial blood flow was evaluated in 15 patients with peripheral atherosclerosis. Flow was determined by quantitative strain-gauge plethysmography; plasma lipid, lipoprotein, and apoprotein levels were repeatedly tested during the cross-over trial, comparing 6 months of drug and placebo administration. Metformin (850 mg tid) significantly increased arterial flow after a standardized ischemia (+17.3% after 3 months and +40.0% after 6 months). The increase in arterial flow was reversible after the switch to placebo was made. The drug was similarly effective, although to a lesser extent (+18.6% after 6 months), when given after the placebo. A highly significant effect of drug treatment, as well as of the sequence of administration, could be established by analysis of variance. In spite of the minimal changes of plasma lipid levels during metformin, a highly significant increase of high density lipoprotein cholesterol (+ 8.3% during the whole treatment) was demonstrated; plasma levels of isoprotein AI-1 were also raised during the metformin period. This controlled experiment confirms data from previous open studies, as well as from a longstanding clinical experience. Although the mechanism of the metformin effect cannot, at present, be defined, the reported results indicate that treatments not markedly affecting plasma lipid-lipoprotein levels may improve vascular function in selected arterial districts.

Adult↗