Tags

Type your tag names separated by a space and hit enter

Fibrate treatment does not modify the expression of acyl coenzyme A oxidase in human liver.
Clin Pharmacol Ther. 2002 Dec; 72(6):692-701.CP

Abstract

BACKGROUND AND OBJECTIVES

Fibrates induce hepatic peroxisome proliferation and carcinogenesis in rodents by activating peroxisome proliferator-activated receptor alpha (PPAR(alpha)). There is no conclusive evidence that humans are unresponsive to peroxisome proliferation, and concern exists about the long-term safety of fibrate treatment.

METHODS

In a university hospital setting, 48 patients with uncomplicated gallstones and a serum level of low-density lipoprotein cholesterol greater than 130 mg/dL were randomly assigned to open-label treatment with bezafibrate (400 mg/d), fenofibrate (200 mg/d), gemfibrozil (900 mg/d), or placebo for 8 weeks before elective cholecystectomy. Serum samples for lipid determinations were obtained at baseline and before surgery. A liver specimen was obtained at operation, and the relative levels of messenger ribonucleic acid (mRNA) for the wild and truncated forms of PPAR(alpha), acyl coenzyme A oxidase, liver carnitine palmitoyltransferase I, apolipoprotein A-I, and stearoyl coenzyme A desaturase were determined.

RESULTS

Fenofibrate, bezafibrate, and gemfibrozil reduced plasma low-density lipoprotein cholesterol levels by 22% (P =.009), 14% (P =.042), and 11% (not significant), respectively. Plasma triglyceride levels decreased significantly (24%-36%; P <.05), whereas high-density lipoprotein cholesterol levels rose nonsignificantly after treatment with the 3 fibrates. Except for a 35% increase of apolipoprotein A-I mRNA after fenofibrate administration (P <.05), none of the individual fibrates induced significant changes in the mRNAs tested, although as a group they increased the mRNA for liver carnitine palmitoyltransferase I by 40%(P =.08; marginally significant).

CONCLUSIONS

Fibrate administration to humans at pharmacologic doses able to activate PPAR(alpha) and to induce a hypolipidemic effect does not increase the hepatic expression of acyl coenzyme A oxidase, a well-known marker of peroxisome proliferation in rodents.

Authors+Show Affiliations

Pharmacology Unit, Faculty of Pharmacy, University of Barcelona, Surgical Department and Lipid Clinic, Nutrition and Dietetics Service, Hospital Clínic i Provincial, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12496750

Citation

Roglans, Núria, et al. "Fibrate Treatment Does Not Modify the Expression of Acyl Coenzyme a Oxidase in Human Liver." Clinical Pharmacology and Therapeutics, vol. 72, no. 6, 2002, pp. 692-701.
Roglans N, Bellido A, Rodríguez C, et al. Fibrate treatment does not modify the expression of acyl coenzyme A oxidase in human liver. Clin Pharmacol Ther. 2002;72(6):692-701.
Roglans, N., Bellido, A., Rodríguez, C., Cabrero, A., Novell, F., Ros, E., Zambón, D., & Laguna, J. C. (2002). Fibrate treatment does not modify the expression of acyl coenzyme A oxidase in human liver. Clinical Pharmacology and Therapeutics, 72(6), 692-701.
Roglans N, et al. Fibrate Treatment Does Not Modify the Expression of Acyl Coenzyme a Oxidase in Human Liver. Clin Pharmacol Ther. 2002;72(6):692-701. PubMed PMID: 12496750.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibrate treatment does not modify the expression of acyl coenzyme A oxidase in human liver. AU - Roglans,Núria, AU - Bellido,Antonia, AU - Rodríguez,Cristina, AU - Cabrero,Agatha, AU - Novell,Ferran, AU - Ros,Emilio, AU - Zambón,Daniel, AU - Laguna,Juan C, PY - 2002/12/24/pubmed PY - 2003/1/22/medline PY - 2002/12/24/entrez SP - 692 EP - 701 JF - Clinical pharmacology and therapeutics JO - Clin Pharmacol Ther VL - 72 IS - 6 N2 - BACKGROUND AND OBJECTIVES: Fibrates induce hepatic peroxisome proliferation and carcinogenesis in rodents by activating peroxisome proliferator-activated receptor alpha (PPAR(alpha)). There is no conclusive evidence that humans are unresponsive to peroxisome proliferation, and concern exists about the long-term safety of fibrate treatment. METHODS: In a university hospital setting, 48 patients with uncomplicated gallstones and a serum level of low-density lipoprotein cholesterol greater than 130 mg/dL were randomly assigned to open-label treatment with bezafibrate (400 mg/d), fenofibrate (200 mg/d), gemfibrozil (900 mg/d), or placebo for 8 weeks before elective cholecystectomy. Serum samples for lipid determinations were obtained at baseline and before surgery. A liver specimen was obtained at operation, and the relative levels of messenger ribonucleic acid (mRNA) for the wild and truncated forms of PPAR(alpha), acyl coenzyme A oxidase, liver carnitine palmitoyltransferase I, apolipoprotein A-I, and stearoyl coenzyme A desaturase were determined. RESULTS: Fenofibrate, bezafibrate, and gemfibrozil reduced plasma low-density lipoprotein cholesterol levels by 22% (P =.009), 14% (P =.042), and 11% (not significant), respectively. Plasma triglyceride levels decreased significantly (24%-36%; P <.05), whereas high-density lipoprotein cholesterol levels rose nonsignificantly after treatment with the 3 fibrates. Except for a 35% increase of apolipoprotein A-I mRNA after fenofibrate administration (P <.05), none of the individual fibrates induced significant changes in the mRNAs tested, although as a group they increased the mRNA for liver carnitine palmitoyltransferase I by 40%(P =.08; marginally significant). CONCLUSIONS: Fibrate administration to humans at pharmacologic doses able to activate PPAR(alpha) and to induce a hypolipidemic effect does not increase the hepatic expression of acyl coenzyme A oxidase, a well-known marker of peroxisome proliferation in rodents. SN - 0009-9236 UR - https://www.unboundmedicine.com/medline/citation/12496750/Fibrate_treatment_does_not_modify_the_expression_of_acyl_coenzyme_A_oxidase_in_human_liver_ L2 - https://doi.org/10.1067/mcp.2002.128605 DB - PRIME DP - Unbound Medicine ER -