Possible role of brown adipose tissue as a mediator during cyclosporine-A treatment.
Cyclosporine-A (CsA) is a potent immunosuppressor used successfully to control rejection in organ transplantation. According to the most recent evidence, this drug modifies the lipid metabolism of the patient, provoking a rise in the blood lipids, constituting an important risk factor for acceleration of the atherogenic process. Taking into account that brown adipose tissue (BAT) constitutes the major storage site for cholesterol and triglycerides in the rat, and given the apparent lack of references about the implications of CsA on this tissue in the literature, we proposed to study the possible morphological changes occurring in BAT following the administration of this drug. Two groups of female Sprague-Dawley rats were set up, the control group and a treated group in which each animal received subcutaneous injection of 5 mg/kg body weight/day of CsA. After 4, 11, 25 and 34 days of treatment, subgroups of animals were sacrificed and the brown adipose tissue removed was apportioned for subsequent microscopic assessment. The greatest degree of atypia and activity in the BAT was observed after administration of 11 doses of the drug, at which point there was a marked reduction in the cell size with loss of lipidic coalescence. With subsequent doses, the tissue slowly initiated a process of recovery. CsA also induced morphological changes in the BAT that, in the early stages of the study, appeared to be correlated with a lipolytic response of the tissue to the drug; thus, the BAT may be acting as a system to eliminate the excess of lipids in the blood provoked by CsA administration, while toward the end of treatment, there was a certain stability between the drug and the activity of the brown adipose tissue, and a tendency to reach a balance between lipolysis and lipogenesis.
Buján
J
J
Department of Morphological Sciences and Surgery, Faculty of Medicine, University of Alcalá de Henares, Madrid, Spain.
Jurado
F
F
Gianonatti
C
C
Contreras
L A
LA
D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000648:ultrastructure; D000818:Animals; D015550:Cell Degranulation; D048429:Cell Size; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D006003:Glycogen / Q000648:ultrastructure; D008055:Lipids; D008247:Lysosomes / Q000648:ultrastructure; D008264:Macrophages / Q000648:ultrastructure; D008407:Mast Cells / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D008055:Lipids; D016572:Cyclosporine; D006003:Glycogen