Aromatic retinoid Ro 40-8757 reduces immunotoxicities of cyclophosphamide as revealed by immunohistochemical staining of lymphoid tissues and general pathologic examinations.
The aromatic retinoid (arotinoid) Ro 40-8757 (4-[2-[p-(E)-2-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) propenyl]phenoxy]ethyl]-morpholine), a compound with antitumor activities, has been studied in a combination therapy with the cytostatic antitumor drug cyclophosphamide (CPA), and was found to protect bone marrow from the toxic effects of CPA. To evaluate its protective effects against CPA toxicities on lymphoid systems, we treated BDF1 mice with Ro 40-8757 orally for 1 to 5 weeks in combination with CPA intraperitoneally. After the combination treatment, mice were subjected to immunohistochemical analysis with antibodies against cell surface markers (Thy 1.2, Lyt-2, L3T4, Kappa chain, and Ia) and, in addition, general pathologic examinations were done. The protective effects of Ro 40-8757 on CPA toxicities were observed. The lymphocyte reductions (both in T cells and B cells) in lymphoid organs by CPA were apparently less severe. In particular, recovery of immature T cells in the thymic cortex was greater in combination treatment with Ro 40-8757 and CPA than in treatment with CPA alone. From these results, it can be concluded that Ro 40-8757 protects the lymphoid organs (thymus, spleen, and lymph node) from the immunotoxicity of CPA, and the protective effect is evident, especially in the thymic cortical lymphocytes.
Inoue
T
T
Department of Preclinical Science, Nippon Roche Research Center, Kanagawa, Japan.
Horii
I
I
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009025:Morpholines / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D012176:Retinoids / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D013997:Time Factors
D000954:Antigens, Surface; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D009025:Morpholines; D012176:Retinoids; C081137:mofarotene; D003520:Cyclophosphamide