Coadministration of olanzapine causes minor impacts on the diabetogenic outcomes induced by dexamethasone treatment in rats

Aims: Investigate whether the coadministration of olanzapine exacerbates the diabetogenic effects of dexa-methasone, two agents used in the antiemetic cocktails indicated to mitigate the adverse effects of chemotherapy.Main methods: Adult Wistar rats (both sexes) were treated daily with dexamethasone (1 mg/kg, body mass (b.m.), intraperitoneal (i.p.)) with or without olanzapine (10 mg/kg, b.m., orogastric (o.g.)) for 5 consecutive days. During and at the end of the treatment, we evaluated biometric data and parameters involving glucose and lipid metabolism.Key findings: Dexamethasone treatment resulted in glucose and lipid intolerance, higher plasma insulin and triacylglycerol levels, higher content of hepatic glycogen and fat, and higher islet mass in both sexes. These changes were not exacerbated by concomitant treatment with olanzapine. However, coadministration of olan-zapine worsened the weight loss and plasma total cholesterol in males, while in females resulted in lethargy, higher plasma total cholesterol, and higher hepatic triacylglycerol release.Significance: Coadministration of olanzapine does not exacerbate any diabetogenic dexamethasone effect on glucose metabolism and exerts a minor impact on the lipid homeostasis of rats. Our data favor the addition of olanzapine in the antiemetic cocktail considering the low incidence of metabolic adverse effects for the period and dosage analyzed in male and female rats.

Automated summary

This study investigated whether the coadministration of olanzapine exacerbates the diabetogenic effects of dexa-methasone in antiemetic cocktails used for chemotherapy. The results showed that the coadministration of olanzapine did not worsen the effects of dexamethasone on glucose metabolism and had only minor effects on lipid homeostasis in rats. Based on these findings, it is recommended to include olanzapine in the antiemetic cocktail due to its low incidence of metabolic adverse effects in male and female rats.