Effect of Sucrose on Cisplatin-induced Fatigue-like Behavior in Mice: Comparison With Fructose and Glucose

Abstract

Background/aim: Fatigue is the most common symptom in patients with cancer undergoing radiation therapy or cancer chemotherapy. However, cancer-related fatigue remains undertreated and poorly understood.

Materials and methods: Mice were administered a single dose of cisplatin (10 mg/kg, intraperitoneally) or saline (as a control) and then treated with sucrose, fructose, glucose (each at 500 or 5,000 mg/kg, orally), or saline (control) daily for 4 days. cisplatin-induced fatigue-like behavior was investigated by assessment of running activity on a treadmill. The influence of glucose intake on tumor growth was also examined in Lewis lung carcinoma (LLC)-bearing mice.

Results: Administration of sucrose and glucose improved cisplatin-induced fatigue-like behavior in mice, whereas administration of fructose showed only slight antifatigue effects. Although glucose-fed mice showed increased tumor growth, this was balanced out by the powerful cytotoxicity of cisplatin.

Conclusion: Sucrose, and especially glucose, may improve patient quality of life during treatment with anticancer agents by preventing fatigue without interfering with the antitumor effects of cisplatin.

Keywords: Cisplatin; fatigue-like behavior; fructose; sucrose.

Figure 1. Experimental timeline (A). Effects of sucrose (B), fructose (C), and glucose (D) in mice subjected to a treadmill fatigue test after treatment with cisplatin (CDDP). Each column represents the mean±standard error of the mean for six mice. Statistical analyses were performed with oneway analysis of variance followed by Tukey’s multiple comparisons tests. Significantly different at: ***p<0.005 vs. the control group; ^#p<0.05, ^##p<0.01, and ^###p<0.005 vs. the CDDP–saline group.

Figure 2. Liver weight and liver glycogen content were measured in mice treated with cisplatin (CDDP) and sucrose (A, B), fructose (C, D), or glucose (E, F). Each column represents the mean±standard error of the mean for six mice. Statistical analyses were performed with one-way analysis of variance followed by Tukey’s multiple comparisons test. Significantly different at: *p<0.05, **p<0.01, and ***p<0.005 vs. the control group; ^#p<0.05, ^##p<0.01, and ^###p<0.005 vs. the CDDP–saline group.

Figure 3. Experimental timeline (A). Effects of glucose or water intake with administration of cisplatin (CDDP) or saline on Lewis lung carcinoma (LLC)-bearing mice. Tumor volume was measured at 8, 10, 12, 14, and 16 days using a Vernier caliper. Tumor volume=length × width × width/2 (B). CDDP-treated mice showed a lower body weight relative to the body weight of control mice (C). Each point represents the mean±standard error of the mean for five mice. Statistical analyses were performed with two-way analysis of variance (ANOVA) followed by Tukey’s multiple comparisons test. Significantly different at: *p<0.05 and **p<0.01 vs. the control group.