OBJECTIVE: The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. MATERIALS AND METHODS: This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. RESULTS: The tumor necrosis rate was significantly higher in the high dose group (93% +/- 7.6 [mean +/- SD]) than that in the control group (48% +/- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +/- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +/- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. CONCLUSION: Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method.
Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Doxorubicin/administration & dosage/pharmacology ; Infusions, Intra-Arterial ; Iodized Oil/administration & dosage/pharmacology ; Liver Neoplasms, Experimental/*drug therapy/radiography ; Pyruvates/administration & dosage/*pharmacology ; Rabbits ; Statistics, Nonparametric ; Tomography, X-Ray Computed

The correlation between muscle glycogen content and physical performance in mice was evaluated by investigating whether an increase in glycogen content in skeletal muscle with insulin administration can improve the physical performance without other effects of exercise. Albino rats(group I) were divided into two groups, i.e., insulin and saline administered group. The former experimental group was treated with protamine zinc insulin(15U/kg/day) subcutaneously for two weeks to increase the content of the muscle glycogen and the latter control group with saline. Mice (group II) were also divided into insulin treated and control groups and both groups were subjected to running exercise on an animal treadmill up to point of exhaustion once every day. After two weeks of insulin treatment, the muscle glycogen content, the maximal running time and the maximal swimming time were measured in non-exercised group I. In group II, after 12 days of insulin and saline administration, the muscle glycogen content, the maximal running time, concentrations of lactate and pyruvate in the blood were measured before and after the maximal exhaustive running. The results were summarized as follows. In group I, the muscle glycogen content, the maximal running time and the maximal swimming time of the insulin administered group were significantly greater of the control groups. In group II, the maximal running time was significantly greater(P < 0.01) in the experimental group than of the control group, while the muscle glycogen content revealed no significant difference between the two groups. On the other hand, lactate concentration and lactate/pyruvate ratios in the blood were significantly lower in the experimental group than those of the control groups. From the above results, it may be concluded that the elevation of muscle glycogen content alone by insulin treatment without any previous physical training can improve physical performance of rats. And insulin was also found to improve physical performance even in experimental animals which had been subjected to a longterm of exercise.
Anaerobiosis/drug effects* ; Animal ; Blood Glucose/analysis ; Body Weight ; Exertion/drug effects* ; Glycogen/analysis* ; Injections, Subcutaneous* ; Insulin/administration & dosage ; Insulin/pharmacology* ; Lactates/blood ; Male ; Metabolism/drug effects* ; Mice ; Muscles/analysis* ; Pyruvates/blood ; Rats