Oral administration of wild plant-derived minerals and red ginseng ameliorates insulin resistance in fish through different pathways.

Many kinds of fish are characterized by a limited efficiency to use carbohydrates. For this reason, raw fish and mixed feed containing a lot of fish meal have been used as feed for fish farming. However, continuing to use high-protein diets not only increases the cost of fish farming, but may also fuel animal protein shortages. Furthermore, carbohydrates are added to improve the texture of the feed and act as a binding agent and are usually contained at 20% in the feed. It makes sense, therefore, to find ways to make good use of carbohydrates rather than wasting them. The physiological mechanisms of glucose intolerance in fish are not yet well understood. Therefore, we investigated the glucose utilization of fish, omnivorous goldfish Carassius auratus and carnivorous rainbow trout Oncorhynchus mykiss. Furthermore, the effects of oral administration of wild plant-derived minerals and red ginseng on the glucose utilization in these fish muscle cells were investigated. As a result, we found the following. (1) An extremely high insulin resistance in fish muscle and the symptom was more pronounced in carnivorous rainbow trout. (2) Administration of wild plant-derived minerals promotes the translocation of the insulin-responsive glucose transporter GLUT4 to the cell surface of white muscle via activation of the PI3 kinase axis, whereas administration of red ginseng not only promotes GLUT4 transfer and translocation to the cell surface of white muscle via AMPK activation as well as promoting glucose uptake into muscle cells via a pathway separate from the insulin signaling system. (3) In fish, at least goldfish and rainbow trout, both PI3K/Akt and AMPK signaling cascades exist to promote glucose uptake into muscle cells, as in mammals.

[Chemopreventive effects of 5-fluorouracil and lactoferrin on goldfish intestinal carcinogenesis induced by 1,2-dimethylhydrazine].

The present study was carried out to examine the chemopreventive effects of 5-fluorouracil (5-FU) and lactoferrin (LF) on goldfish intestinal carcinogenesis induced by 1,2-dimethylhydrazine (DMH). DMH was given to fish by intraperitoneal injection in a dosage of 15 mg/kg body weight once a week for 6 weeks. Eight weeks after the initial DMH injection, fish were randomly divided into 2 groups, control and LF-treated groups. Control fish fed a commercial diet. LF- treated fish fed a commercial diet with bovine lactoferrin (oral administration at 200 mg/kg body weight/day). Ten weeks after the initial DMH injection, each was divided into 2 groups, saline- and 5-FU- treated groups. Physiological saline for freshwater fish (0.75% NaCl solution) in the saline-treated fish and 5-FU dissolved in 0.75% NaCl solution in the 5-FU-treated (75 mg/kg body weight) fish were injected intramuscularly three times every other day, respectively. The mean number of precancer cell foci (PCF) per intestine was 2.7 in DMH treated fish. PCF showed broader distribution in the entire intestine derived from DMH-treated fish. LF-only-treatment has no effect on the number of PCF. Mean number of PCF in 5-FU-only-treated fish decreased in comparison with that of the saline-treated control group, though no statistically significant reduction in PCF was found. But if 5-FU treatment was added to LF pretreatment, a statistically significant reduction in the number of PCF was observed. Pretreatment with LF for 2 weeks also reduced the deleterious side effects of 5-FU.

[Lactoferrin reduces physiological dysfunctions of goldfish induced by chemotherapeutic agents].

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.