Synergistic Effect of Docetaxel Plus Saponin Fraction of Vitex doniana on Prostate Specific Antigen and p53 in Nitrsobis (2-oxopropyl) Amine-induced Prostate Toxicity

Abstract

Aim: This study investigated the synergistic effect of docetaxel plus saponin fraction of Vitex doniana on prostate specific antigen and p53 in nitrsobis (2-oxopropyl) amine-induced prostate toxicity in Wistar rat. Methodology: Twenty-four (24) male Wistar rats with elevated serum prostate specific antigen level were selected from a group of sixty (60) rats pretreated with subcutaneous Nitrosobis (2-oxopropyl) amine 5 mg/kg daily for 4 weeks. The selected 24 male Wistar rats were then grouped into 6 groups of four (4) rats each. Group 1 was given 1ml normal saline daily from day 1-28. Groups 2, 3, 4, 5, and 6 further received subcutaneous nitrosobis (2-oxopropyl) amine 5 mg/kg daily from day 1-28. In addition, groups 3, 4, 5, and 6 were given weekly intravenous docetaxel 8 mg/kg on day 15 and 22. In addition to docetaxel, groups 4, 5, and 6 were further treated with oral saponin at 250 mg/kg, 500 mg/kg, and 750 mg/kg, respectively, daily, from day 15-28. Immunoenzymometric assay method was used for analysis of blood sample for prostate specific antigen. The prostate tissues were subjected to immuno study using the ImmunoCruz Staining System (Lab Vision Corporation, Fremont, CA, USA). The quantitative evaluation of p53 was done by calculating the percentages of p53-immunostained nuclei (labeling index). Results: Significant increase in prostate specific antigen and p53 expression were observed in group 2 (treated with Nitrsobis (2-oxopropyl) amine alone) when compared with group 1 (control). Dose dependent decrease in prostate specific antigen and p53 expression were observed in groups 4, 5, and 6, treated with docetaxel 8 mg/kg plus 250 mg/kg, 500 mg/kg, and 750 mg/kg of saponin respectively. Conclusion: Docetaxel plus Saponin fraction of Vitex doniana significantly reduced the serum prostate specific antigen concentration and p53 expression in a dose dependent manner, with the group treated with 750 mg/kg showing the highest decrease in the parameters tested.