title: FTY720 mitigates torsion/detorsion-induced testicular injury in rats.
abstract: BACKGROUND
  FTY720, a sphingosine-1-phosphate (S1P) receptor agonist, possesses potent anti-inflammation capacity. We evaluated the therapeutic potentials of FTY720 against testicular injury induced by testicular torsion and/or detorsion (T/D).
  
  
  METHODS
  Young adult male Sprague-Dawley rats were allocated to receive T/D (the T/D group) and T/D plus FTY720 (4 mg/kg, the T/D-FTY group, n = 6 in each group). To investigate the possible roles of the S1P receptors, another group of rats received T/D plus FTY720 plus the potent S1P receptor antagonist VPC23019 (1 mg/kg, the T/D-FTY-VPC group, n = 6). FTY720 was administered immediately before testicular detorsion, and VPC23019 was administered 30 min before FTY720. Another set of rats that received sham operation, immediately followed by injection of normal saline, FTY720, or FTY720 plus VPC23019, served as control groups. Sham control groups were run simultaneously. After euthanization, levels of testicular injury were measured.
  
  
  RESULTS
  Histologic findings revealed severe testicular injury changes in both the T/D and T/D-FTY-VPC groups and moderate testicular injury changes in the T/D-FTY group. In addition, malondialdehyde activity (oxidative status), concentration of interleukin-1β (inflammation index), myeloperoxidase activity (neutrophil infiltration index), and wet-to-dry weight ratio (tissue edema index) of both the T/D and T/D-FTY-VPC groups were significantly higher than those of the T/D-FTY group. These data confirmed the protective effects of FTY720 against testicular T/D. Moreover, antagonizing the S1P receptors could reverse the protective effects of FTY720.
  
  
  CONCLUSIONS
  FTY720 significantly mitigated testicular injury induced by testicular T/D. The mechanisms may involve activating the S1P receptors.
authors: Division of Urology, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors: Hung-Jen
authors: HJ
authors: Shih
authors: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors: Jiin-Cherng
authors: JC
authors: Yen
authors: School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Allen W
authors: AW
authors: Chiu
authors: Department of Urology, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Medical College, Taipei, Taiwan.
authors: Yung-Chiong
authors: YC
authors: Chow
authors: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors: Wynn H T
authors: WH
authors: Pan
authors: Department of Pathology, Mackay Memorial Hospital, Taipei, Taiwan.
authors: Tao-Yeuan
authors: TY
authors: Wang
authors: Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan. Electronic address: huangcj1112@gmail.com.
authors: Chun-Jen
authors: CJ
authors: Huang
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000188:drug therapy; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D011409:Propylene Glycols / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013086:Spermatic Cord Torsion / Q000188:drug therapy*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D013737:Testis / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
keywords: Ischemia; Reperfusion; Sphingosine-1-phosphate; Testis; Torsion