pantetheine and Liver-Diseases

A randomized and double blind experiment has been made over 50 patients and 25 checks, by giving a dosage of 3 Fosfolip (calcium salt of phosphorylcholine chlorid with pantethine) capsules a day. The analysis results has been reported in the work. In none case the product had secondary no desired effects; while therapeutical possibilities have been resulted in hepatosis, dyslipidosis and as energetic tonic in atherosclerotic subjects.

Topics: Adult; Aged; Arteriosclerosis; Choline; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Female; Humans; Hyperlipidemias; Lipids; Liver Diseases; Male; Middle Aged; Pantetheine; Phosphorylcholine; Sulfhydryl Compounds

Pretreatment of mice with the peroxisome proliferator clofibrate (CFB) protects against acetaminophen (APAP)-induced hepatotoxicity. Previous studies have shown that activation of the nuclear peroxisome proliferator activated receptor-alpha (PPARalpha) is required for this effect. The present study utilizes gene expression profile analysis to identify potential pathways contributing to PPARalpha-mediated hepatoprotection. Gene expression profiles were compared between wild type and PPARalpha-null mice pretreated with vehicle or CFB (500 mg/kg, i.p., daily for 10 days) and then challenged with APAP (400 mg/kg, p.o.). Total hepatic RNA was isolated 4 h after APAP treatment and hybridized to Affymetrix Mouse Genome MGU74 v2.0 GeneChips. Gene expression analysis was performed utilizing GeneSpring software. Our analysis identified 53 genes of interest including vanin-1, cell cycle regulators, lipid-metabolizing enzymes, and aldehyde dehydrogenase 2, an acetaminophen binding protein. Vanin-1 could be important for CFB-mediated hepatoprotection because this protein is involved in the synthesis of cysteamine and cystamine. These are potent antioxidants capable of ameliorating APAP toxicity in rodents and humans. HPLC-ESI/MS/MS analysis of liver extracts indicates that enhanced vanin-1 gene expression results in elevated cystamine levels, which could be mechanistically associated with CFB-mediated hepatoprotection.

Topics: Acetaminophen; Acyl-CoA Oxidase; Amidohydrolases; Animals; Anticholesteremic Agents; Cell Adhesion Molecules; Chemical and Drug Induced Liver Injury; Clofibrate; Cluster Analysis; Cystamine; Cysteamine; Enoyl-CoA Hydratase; Gene Expression Profiling; GPI-Linked Proteins; Liver; Liver Diseases; Malate Dehydrogenase; Male; Mice; Mice, Inbred Strains; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Pantetheine; Pantothenic Acid; Peroxisome Proliferators; PPAR alpha; Proteasome Endopeptidase Complex; Reverse Transcriptase Polymerase Chain Reaction

Topics: Adult; Aged; Choline; Chronic Disease; Drug Combinations; Female; Humans; Liver Diseases; Male; Middle Aged; Pantetheine; Phosphorylcholine; Sulfhydryl Compounds

Topics: Carbon Tetrachloride; Diet; Lipotropic Agents; Liver Diseases; Pantetheine; Pantothenic Acid; Sulfides