The in vivo effect of the administration of resistance-modulating agents on rhodamine 123 distribution in mice thymus and lymph nodes.
P-glycoprotein (Pgp) has been widely associated with the multidrug resistance phenotype. Nevertheless, this protein has been detected in many normal tissues and cells, including liver, kidney, endothelial cells that constitute the hematological barrier of the brain and testes, and cells from the immune system. Many in vitro models have been used to study drugs that modulate Pgp activity and the multidrug resistance phenomenon. In the present work, we investigate the in vivo effects of resistance-modulating agents on lymphoid organs. Rhodamine 123 (Rho123), a well-known Pgp substrate, was administered to mice, and the fluorescence level in thymus and lymph node cells measured. The fluorescence level on these organs showed a dose-dependent response. Cyclosporin A (CSA), Verapamil (VP) and Trifluoperazine (TFP), three resistance-modulating agents, were administered to mice 1 h prior to 1 mg/kg Rho123 administration. Surprisingly, VP (10 mg/kg) and TFP (750 microg/kg) did not modulate Rho123 retention by thymus and lymph node cells. CSA (50 mg/kg) was the only drug that increased the fluorescence level in both organs. These results point out to the need of a wider study on the in vivo effects of resistance-modulating agents in different organs and systems.
Marques-Santos
L F
LF
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil. lfmarques@bioqmed.ufrj.br
Harab
R C
RC
de Paula
E F
EF
Rumjanek
V M
VM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008198:Lymph Nodes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020112:Rhodamine 123 / Q000493:pharmacokinetics*; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005456:Fluorescent Dyes; D007166:Immunosuppressive Agents; D020112:Rhodamine 123; D016572:Cyclosporine