2007 年 127 巻 9 号 p. 1449-1460
We investigated whether the deleterious side effects of chemotherapeutic agents on the physiologic functions of fish could be modulated by lactoferrin (LF). Goldfish, weighing about 25 g, were treated intramuscularly with methotrexate (MTX: 2.5 mg/kg body weight) and fluorouracil (FU: 15 or 50 mg/kg body weight) three times every other day. In control fish fed a commercial diet, MTX induced severe immunosuppression, increased the number of total bacteria and Enterobacteriaceae in the intestinal tract, and caused intestinal damage such as lowered and thickened mucosa and thinned muscularis externa, with moderate renal dysfunction. A few fish treated with MTX died. In fish injected with FU or FU plus MTX, the side effects were slightly less in comparison with those in the MTX group. Pretreatment with LF (oral administration at 200 mg/kg body weight/day) for 3 weeks reduced the deleterious side effects of MTX and FU. One intraperitoneal injection of LF (200 mg/kg body weight) immediately after the first MTX injection also reduced the side effects. These results show that LF reduces the physiologic dysfunction of fish treated with chemotherapeutic agents.