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 rec ent evidence, this drug modifies the lipid metabolism of the patient, provoking a rise in the blood lipids, constituting an important risk f actor for acceleration of the atherogenic process. Taking into account that brown adipose tissue (BAT) constitutes the major storage site fo r cholesterol and triglycerides in the rat, and given the apparent lac k of references about the implications of CsA on this tissue in the li terature, we proposed to study the possible morphological changes occu rring in BAT following the administration of this drug. Two groups of female Sprague-Dawley rats were set up, the control group and a treate d group in which each animal received subcutaneous injection of 5 mg/k g body weight/day of CsA. After 4, 11, 25 and 34 days of treatment, su bgroups of animals were sacrificed and the brown adipose tissue remove d was apportioned for subsequent microscopic assessment. The greatest degree of atypia and activity in the BAT was observed after administra tion of 11 doses of the drug, at which point there was a marked reduct ion in the cell size with loss of lipidic coalescence. With subsequent doses, the tissue slowly initiated a process of recovery. CsA also in duced morphological changes in the BAT that, in the early stages of th e study, appeared to be correlated with a lipolytic response of the ti ssue 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, whi le 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.