Strontium fructose 1, 6-diphosphate alleviate cyclophosphamide-induced oligozoospermia by improving antioxidant and inhibiting testicular apoptosis via FAS/FASL pathway

Andrologia. 2015 Nov;47(9):995-1003. doi: 10.1111/and.12369. Epub 2014 Nov 8.

Abstract

This study investigated the treatment effects of a new compound, strontium fructose 1, 6-diphosphate (FDP-Sr), in cyclophosphamide (CP)-induced oligozoospermia. FDP-Sr, with extra high-energy supply, could reverse male hypogonadism in the testis. Male Wistar rats were randomly divided into three groups: control group (vehicle treated), CP group and CP + FDP-Sr group. Both CP group and CP + FDP-Sr groups were orally administered CP (20 mg kg(-1) ) consecutively for the first 7 days to establish CP-induced testicular toxic models. Subsequently, CP group was given orally distilled water per day, whereas CP + FDP-Sr group was received FDP-Sr (200 mg kg(-1) ) for 49 days. Compared to the CP group, the FDP-Sr group showed significantly increased levels of serum testosterone, testis relative weights and epididymal sperm counts in rats. In addition, rats treated by FDP-Sr showed the recuperative activities of testicular marker enzymes and normalised levels of antioxidants in tissue. Testicular protection of FDP-Sr was further demonstrated by enhancing expression of P450scc, reducing ability of FAS/FASL and generating cytoprotection in the histopathological study. FDP-Sr appeared to possess an ability to attenuate CP-induced reproduction toxicity via the activation of antioxidants and steroidogenesis enzymes, and alleviate oligozoospermia via inhibition of testicular apoptosis by FAS/FASL pathway.

Keywords: Cyclophosphamide; oligozoospermia; strontium fructose 1, 6-diphosphate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / toxicity
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cyclophosphamide / toxicity
  • Disease Models, Animal
  • Fas Ligand Protein / drug effects
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / metabolism
  • Fructosediphosphates / pharmacology*
  • Glutathione / drug effects
  • Glutathione / metabolism
  • Glutathione Peroxidase / drug effects
  • Glutathione Peroxidase / metabolism
  • L-Iditol 2-Dehydrogenase / drug effects
  • L-Iditol 2-Dehydrogenase / metabolism
  • L-Lactate Dehydrogenase / drug effects
  • L-Lactate Dehydrogenase / metabolism
  • Lipid Peroxides / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Oligospermia / chemically induced
  • Oligospermia / metabolism*
  • Organ Size / drug effects
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sperm Count
  • Sperm Retrieval
  • Superoxide Dismutase / drug effects
  • Superoxide Dismutase / metabolism
  • Testis / anatomy & histology
  • Testis / drug effects*
  • Testosterone / blood
  • fas Receptor / drug effects
  • fas Receptor / genetics
  • fas Receptor / metabolism
  • gamma-Glutamyltransferase / drug effects
  • gamma-Glutamyltransferase / metabolism

Substances

  • Antineoplastic Agents, Alkylating
  • Antioxidants
  • Fas Ligand Protein
  • Fas protein, rat
  • Faslg protein, rat
  • Fructosediphosphates
  • Lipid Peroxides
  • fas Receptor
  • Testosterone
  • Malondialdehyde
  • Cyclophosphamide
  • L-Iditol 2-Dehydrogenase
  • L-Lactate Dehydrogenase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • gamma-Glutamyltransferase
  • Glutathione
  • fructose-1,6-diphosphate