Hypothesis / aims of study
Advances in anti-cancer drug treatment have saved many lives, while measures to prevent the late effects of anti-cancer drug treatment have become more important. Anti-cancer drugs, such as platinum anti-cancer drugs, cause side effects such as peripheral neuropathy, which continues to cause problems even after anti-cancer drug treatment has ended. At a previous ICS meeting, we reported that male rats treated with oxaliplatin (L-OHP) showed a prolonged micturition interval and decreased detrusor muscle contraction. In this study, we investigated the effect of L-OHP on bladder contractility using female rats.
Study design, materials and methods
Female Wistar-ST rats aged 8 weeks were divided into two groups: a Control group and an L-OHP group (n=6 each). The L-OHP group was administered L-OHP diluted in 5% glucose solution at a dose of 4 mg/kg. L-OHP was administered intravenously on days 1, 2, 8, 9, 15, 16, 22, and 23. The Control group received only the 5% glucose solution intravenously. A 4-week observation period was set, and the pharmacological evaluation of urinary muscle contraction force was conducted using cumulative doses of acetylcholine (ACh) on excised rat bladders.
Results
The body weight of the L-OHP group was significantly lower than that of the Control group from 2 weeks onward, and at 4 weeks, it was 244.3 ± 3.9 g in the Control group and 205.7 ± 2.6 g in the L-OHP group (P < 0.01). On the other hand, the bladder weight at 4 weeks was significantly heavier in the L-OHP group than in the Control group (Control group: 84.3 ± 3.4 mg, L-OHP group: 108.7 ± 5.8 mg; P < 0.01). As a result of isometric tension measurements, the L-OHP group showed a tendency for reactivity to ACh to decrease compared to the Control group (P = 0.08). In particular, the maximum contractile response at 100 μM of ACh was 683.0 ± 204.1 N/g in the Control group and 471.1 ± 93.5 N/g in the L-OHP group.
Interpretation of results
By administering the anticancer drug L-OHP, an increase in bladder weight and a decrease in detrusor muscle contraction were observed. In this study, we examined the method of creating a peripheral neuropathy model rat, and found that female rats treated with L-OHP as well as male rats had a decrease in detrusor muscle contractility, which is thought to have caused an increase in bladder weight. Subsequently, we would like to consider histological evaluation of the bladder and evaluation of urinary function. It is also necessary to examine the effect on detrusor muscle contraction force after L-OHP administration. We would also like to examine the urinary function of cancer survivors after anticancer drug treatment.