betadex and Liver-Diseases--Alcoholic

In patients with non-insulin dependent diabetes mellitus (T2DM) and associated chronic liver disease, plasma levels of glucose, insulin and triglycerides are high, lipid peroxidation is increased and natural antioxidant reserves are reduced. Thus, we hypothesised that the re-balancing of cell redox levels and amelioration of liver function could result in a better glucose and lipid metabolism. To study this, we assessed the effect of a new oral formulation of an antioxidant agent - silybin-beta-cyclodextrin (named IBI/S) - in patients with chronic alcoholic liver disease and concomitant T2DM.. Sixty outpatients were enrolled in a three-centre, double blind, randomised, IBI/S vs placebo study. Forty-two (21 in the group IBI/S - 135 mg/d silybin per os - and 21 in the placebo group) concluded the 6-month treatment period. The efficacy parameters included fasting and mean daily plasma glucose levels, glycosylated hemoglobin (HbA1c), basal, stimulated C-peptide and insulin levels, total-, HDL-cholesterol and triglycerides levels in addition to conventional liver function tests. Insulin sensitivity was estimated by HOMA-IR. Malondialdehyde (MDA) was also measured before and after treatment as an index of oxidative stress.. Fasting blood glucose levels, which were similar at baseline in IBI/S group and in the placebo group (173.9 mg/dl and 177.1 mg/dl, respectively), decreased to 148.4 mg/dl (-14.7% vs baseline; p = 0.03) in the IBI/S group while they were virtually unchanged in the placebo group. The comparison between the groups at mo 6 (T6) also showed a significant reduction of glucose levels in the IBI/S group (p = 0.03). The same trend was observed in mean daily blood glucose levels, HbA1c and HOMA-IR, although differences were not significant. Basal and stimulated C-peptide values showed that only a few changes had occured in both groups. Such results indicate that insulin secretion was virtually unaffected, as confirmed also by the insulinemia data. Plasma triglycerides concentrations dropped from a baseline value of 186 mg/dl to 111 mg/dl (T6) in the IBI/S group, with significant differences at all instances with respect to baseline values. By contrast, triglycerides increased from 159 mg/dl at entry to 185 mg/dl (T6) in the placebo group. The difference between the groups at T6 was highly significant (p < 0.01). Total and HDL cholesterol as well as liver function tests did not change significantly during the study in both groups. MDA decreased significantly only in the group receiving IBI/S. No clinically relevant side effects were observed in either group.. Oral administration silybin-beta-cyclodextrin in patients with T2DM and compensated chronic alcoholic liver disease causes a significant decrease in both glucose and triglyceride plasma levels. These effects may be due to the recovery of energy substrates, consistent with a reduced lipid peroxidation and an improved insulin activity.

Topics: Antioxidants; beta-Cyclodextrins; Blood Glucose; C-Peptide; Cholesterol, HDL; Cyclodextrins; Diabetes Mellitus, Type 2; Double-Blind Method; Female; gamma-Glutamyltransferase; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Liver Diseases, Alcoholic; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Placebos; Silybin; Silymarin; Triglycerides

To prepare the sustained-release complex, quercetin was incorporated with β- cyclodextrin (β-CD) and the effect of β-CD-quercetin complex on the growth of ethanol-injuried hepatocytes was studied.. By using scanning electron microscopy, infrared spectroscopy, and release rate analysis, β- CD-quercetin complex was identified. The effect of different concentrations of β-CD-quercetin complex on the growth of ethanol-damaged hepatocytes at different time was observed by using MTT assay, and the cell quantity and morphology were observed by using hematoxylin-eosin staining. By using single-cell gel electrophoresis, the prevention of β-CD-quercetin complex from the DNA damage of ethanol-damaged BRL-3A cells was studied, and Olive tail moment was calculated.. β-CD-quercetin complex as the sustained-release complex was successfully prepared. The ethanol induced damage of BRL-3A cells could be prevented by 20, 40 and 80 mg/L of quercetin complex, and the protection mechanism of hepatocyte was related to the antioxidation of DNA.. Quercetin sustained-release complex could be prepared with β-CD, and it might be used to treat alcoholic liver disease.

Topics: Animals; Antioxidants; beta-Cyclodextrins; Cell Line; Delayed-Action Preparations; Disease Models, Animal; DNA Damage; Drug Compounding; Ethanol; Hepatocytes; Humans; Liver Diseases, Alcoholic; Oxidative Stress; Pharmaceutic Aids; Quercetin; Rats; Solubility