Tocotrienol rich fraction supplementation confers protection on the ovary from cyclophasphamide induced apoptosis

Abstract

IntroductionCyclophosphamide (CPA) therapy leads to infertility via oxidative stress induced apoptosis of ovarian cells. Tocotrienol, vitamin E isoform, is a much more potent antioxidant compared to tocopherol, the more investigated vitamin E isoform. Tocotrienol rich fraction (TRF) is an affordable and available form of tocotrienol supplementation. The effect of concurrent TRF supplementation with CPA treatment is un-investigated. ObjectiveTo study the ovarian protective effect of tocotrienol rich fraction (TRF) when coadministered with CPA. Methods60 female ICR mice, aged between 8 −10 weeks were divided into 5 treatment groups: CPA, CPA&TRF, normal saline, TRF only, and corn oil (TRF carriage vehicle) only. The treatment was given for 30 consecutive days, after which all animal were euthanized. At dissection, both ovaries were removed, fixed in 10% formalin, processed and embedded in paraffin to form tissue blocks. Terminal deoxynucleotidyl transferase–mediated deoxy-uridine triphosphate nick-end labelling (TUNEL) assay was performed on the tissue blocks. Results & DiscussionThere was a significant reduction of TUNEL positive cells in the combined CPA&TRF group compared to CPA only group (p<0.05). All ovaries in normal control group showed only occasional TUNEL–positive cells, mostly confined to atretic follicles. No increase in TUNEL positive cells were seen in the TRF and oil only control groups. ConclusionCo administration of TRF with CPA confers protection against apoptosis in ovaries. TRF is a potential candidate for ovarian conservation in chemotherapy associated damage.