Abstract
BackgroundAlthough cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors. Previous studies reported that chronotherapy decreased CDDP-induced nephropathy and vomiting. In the present study, we investigated the influence of dosing times on CDDP-induced peripheral neuropathy in rats.MethodsCDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague–Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed.ResultsIn order to estimate hypoalgesia, the hot-plate test was performed in rats administered CDDP weekly for 4 weeks. On day 28, the withdrawal latency to thermal stimulation was significantly prolonged in the 17:00-treated group than in the control and 5:00-treated groups. When the von-Frey test was performed to assess mechanical allodynia, the withdrawal threshold was significantly lower in the 5:00 and 17:00-treated groups than in the control group on day 6 after the first CDDP dose. The 5:00-treated group maintained allodynia throughout the experiment with the repeated administration of CDDP, whereas the 17:00-treated group deteriorated from allodynia to hypoalgesia.ConclusionsIt was revealed that the severe of CDDP-induced peripheral neuropathy was inhibited in the 5:00-treated group, whereas CDDP-treated groups exhibited mechanical allodynia. These results suggested that the selection of an optimal dosing time ameliorated CDDP-induced peripheral neuropathy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2777-0) contains supplementary material, which is available to authorized users.
Highlights
Cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors
It is extensively used in the treatment of non-small cell lung, head and neck, ovarian, and breast cancers [3,4,5,6], and exhibits strong therapeutic effects in cancer chemotherapy
CDDP is the main drug used in chemotherapy, it has dose-limiting adverse effects such as peripheral neuropathy, nephropathy, and vomiting, which limit the continuation of chemotherapy [7,8,9]
Summary
CDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague–Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed. Animals Male Sprague–Dawley (SD) rats (6 weeks old) were purchased from Japan SLC, Ltd. All rats were kept under these conditions for 1 week until used in experiments, and the body weights were 220–260 g at point of starting experiments. Experiments were performed after formal approval by the Committee for Animal Experiments at the University of Toyama. Its final concentration was 2 mg/mL (4 mg/kg) in each dosing group. CDDP was intravenously (i.v.) administered at 2 mL/kg to rats
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
