Additional dexamethasone in chemotherapies with carboplatin and paclitaxel could reduce the impaired glycometabolism in rat models

Abstract

Background

Side-effects have been considered as the limitation of the chemotherapy agents' administration and life quality in patients with ovarian cancers. In order to explore the influence of the chemotherapy agents commonly used in ovarian cancer patients on the blood glucose metabolism in rat models, we conducted this study which simulated the conditions of clinical protocols.

Methods

Eighty clean-grade female Wistar rats were randomized into 8 groups: Group 1 (Negative control), Group 1′ (Dexamethasone), Group 2 (Carboplatin), Group 2′ (Carboplatin-plus-dexamethasone), Group 3 (Paclitaxel), Group 3′ (Paclitaxel-plus-dexamethasone), Group 4 (Combined therapy), Group 4′ (Combined-therapy-plus-dexamethasone). On day 0, 4, 7 and 14, after fasted for 12 h, the rats in all groups underwent a glucose load and their blood glucose, glucagon and insulin levels were measured.

Results

The glucose levels in group 2, 3 and 4 at 1 h after the loading on day 4 significantly increased (P = 0.190, 0.008 and 0.025, respectively). The glucagon levels in group 3 and 4 showed a similar trend and the increase was not suppressed by the glucose loading (P < 0.001). A significant decrease of insulin levels in group 2, 3 and 4 were observed on day 14 after treatment (P = 0.043, 0.019 and 0.019, respectively). The change of HOMA2 %B, an index reflects the ability of insulin secretion was negatively corresponded to the glucose levels, and the trends of HOMA2 IR, an index shows insulin resistance, were positively correlated to the glucose levels. The application of dexamethasone could reduce the degree of increased glucose levels significantly in group 2, 3 and 4. There were no differences in overall survival between the 8 groups. Edema in the stroma of pancreases was observed in group 3, 3′, 4 and 4′ on day 4 after treatment (P = 0.002, 0.002, 0.000 and 0.000 respectively) and lasted until day 14.

Conclusions

Carboplatin and paclitaxel administration could cause a transient hyperglycemia in rats. This effect might occur by the combination of glucagon accumulation due to the decrease in islet cell secretion. The additional dexamethasone in the combination protocol of carboplatin and paclitaxel seemed to reduce the impaired blood glucose metabolism.

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