Effects of Valproic Acid and Temozolomide on the Liver of Rats Immunosuppressed by Dexamethasone

Abstract

 Introduction: Temozolomide and valproic acid are used in the treatment of glioblastoma. Animal experiments on this topic require strong immunosuppression with dexamethasone. There is insufficient work on the combined effect of these three drugs on the liver.

 Aim: To examine the effects of valproic acid and temozolomide on the liver of rats immunosuppressed by dexamethasone.

 Materials and Methods: In our experiment, we used 20 male Wistar albino rats. All animals were anesthetized, and the human glioblastoma U87 cell line was inoculated. Dexamethasone (1.5 mg/kg) was given on the day before inoculation, and afterwards on every other day. Cefadroxil was used to prevent infection. Animals were divided into 4 groups: control group receiving only dexamethasone, T group receiving dexamethasone and temozolomide, V group receiving dexamethasone and temozolomide, and TV group receiving dexamethasone, temozolomide, and valproic acid. Temozolomide was given from the 8th to the 10th day, and valproic acid from the 6th to the 12th day from the day of inoculation of the cell line. The sacrifice was performed on the 14th day after inoculation. Liver incisions were made and staining was performed: hematoxylin-eosin, Masson's, and periodic acid–Schiff. 

 Results: Ballooning degeneration of the liver and positive periodic acid–Schiff staining appear on all samples, but the degree of change differs from one group to another.

 Conclusion: Treatment of rats immunosuppressed with high doses of dexamethasone with temozolomide worsened the ballooning degeneration of hepatocytes, while treatment with temozolomide and valproic acid alleviated ballooning degeneration but intensified glycogen accumulation. Valproic acid, in cooperation with dexamethasone, alleviated ballooning degeneration and glycogen accumulation.