Rosiglitazone-induced protection against myelotoxicity produced by 5-fluorouracil.
Insulin promotes survival of haemopoietic progenitors. We investigated if rosiglitazone, an insulin sensitizer, could confer protection against 5-fluorouracil (5-FU)-induced myelotoxicity in mice. The decrease in bone marrow cellularity, frequency and content of granulocyte-macrophage progenitors (CFU-GM) characterized myelotoxicity in mice, while insulin sensitivity was determined by hyperinsulinaemic euglycaemic glucose clamping. CFU-GM colony numbers increased in groups pre-treated with rosiglitazone (1.5-6 mg/kg, 5 days), compared to that in mice treated with 5-fluorouracil alone. Since rosiglitazone pre-treatment significantly promoted the clonal expansion of CFU-GM when given in the insulin sensitizing dose, we conclude that rosiglitazone had myeloprotective effects possibly by amplifying endogenous insulin action.
D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D003114:Colony-Forming Units Assay; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D006098:Granulocytes / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007333:Insulin Resistance; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D020011:Protective Agents / Q000494:pharmacology*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D007004:Hypoglycemic Agents; D020011:Protective Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005472:Fluorouracil