title: Tocotrienol preserves ovarian function in cyclophosphamide therapy.
abstract: BACKGROUND
  Cyclophosphamide (CPA) chemotherapy leads to ovarian failure and infertility. Tocotrienol (T3) is an antioxidant and anti-inflammatory agent. The role of T3 in ovarian protection throughout chemotherapy remains unclear.
  
  
  OBJECTIVE
  To investigate the role of T3 in the preservation of female fertility in CPA treatment.
  
  
  METHODS
  Sixty female mice were divided into five treatment groups, namely, normal saline, corn oil only, T3 only, CPA and CPA + T3. The treatment was given for 30 days, followed by administration of gonadotrophin to induce ovulation. After killing, both ovaries were collected and examined histologically.
  
  
  RESULTS
  There was significant reduction in ovarian size in the CPA group compared with the normal group (CPA versus normal, mean area ± SD; 0.118 ± 0.018 vs. 0.423 ± 0.024 cm(2); p ≤ 0.005), whilst concurrent administration of T3 with CPA leads to conservation of ovarian size (CPA + T3 vs. CPA, mean area ± SD; 0.285 ± 0.032 vs. 0.118 ± 0.018 cm(2); p ≤ 0.005). Ovaries in CPA group showed abnormal folliculogenesis with accompanied reduced ovulation rate, follicular oedema, increased vascularity and inflammatory cell infiltration. These changes were reversed by concurrent T3 administration.
  
  
  CONCLUSIONS
  Co-administration of T3 with CPA confers protection of ovarian morphology and function in vivo. These findings contribute to the further elucidation of CPA effect on ovary and suggest the potential of T3 use in preserving fertility in chemotherapy.
authors.affiliation: Faculty of Health Science, Universiti Teknologi MARA, Puncak Alam, Selangor, Malaysia Department of Biology, Faculty of Pure Science Education, Thi-Qar University, Thi-Qar, Iraq.
authors.forename: H S
authors.initials: HS
authors.lastname: Saleh
authors.affiliation: Faculty of Medicine, Institute of Medical Molecular Biotechnology, Universiti Teknologi MARA, Sg Buloh, Selangor, Malaysia Centre for Pathology Diagnostic and Research Laboratories, Universiti Teknologi MARA, Sg Buloh, Selangor, Malaysia effat@salam.uitm.edu.my.
authors.forename: E
authors.initials: E
authors.lastname: Omar
authors.affiliation: Faculty of Medicine, Institute of Medical Molecular Biotechnology, Universiti Teknologi MARA, Sg Buloh, Selangor, Malaysia.
authors.forename: G R A
authors.initials: GR
authors.lastname: Froemming
authors.affiliation: Faculty of Health Science, Universiti Teknologi MARA, Puncak Alam, Selangor, Malaysia.
authors.forename: R M
authors.initials: RM
authors.lastname: Said
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000633:toxicity*; D005260:Female; D051379:Mice; D010053:Ovary / Q000187:drug effects* / Q000473:pathology; D024508:Tocotrienols / Q000494:pharmacology*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000975:Antioxidants; D024508:Tocotrienols; D003520:Cyclophosphamide
keywords: Cyclophosphamide; folliculogenesis; in vivo; ovary; tocotrienol