title: Estrogen and DPP-4 inhibitor share similar efficacy in reducing brain pathology caused by cardiac ischemia-reperfusion injury in both lean and obese estrogen-deprived rats.
abstract: OBJECTIVE
  Cardiac ischemia-reperfusion injury (I/R) caused an oxidative burst, increased beta-amyloid production, and decreased dendritic spine density in the brain. However, the effect of cardiac I/R in the brain of estrogen-deprived rats who were or were not obese have not been investigated. Moreover, the benefits of estrogen or dipeptidyl peptidase-4 (DDP-4) inhibitor therapies in those conditions have never been determined. We hypothesized that cardiac I/R aggravates brain pathology in estrogen-deprived obese rats, to a greater extent when compared with estrogen-deprived lean rats, and treatment with either estrogen or a DPP-4 inhibitor attenuates those adverse effects.
  
  
  METHODS
  In protocol 1, rats were divided into sham operation (n = 12) or ovariectomy (n = 24). Sham-operated rats were fed with normal diet (ND) and ovariectomized rats were fed with either ND or high-fat diet (HF) for 12 weeks. Then, rats were subdivided to sham operation or cardiac I/R injury. In protocol 2, ovariectomized rats were given either ND (n = 18) or HF (n = 18). At week 13, ovariectomized rats were subdivided to receive vehicle, estradiol, or DPP-4 inhibitor for 4 weeks. Then, all rats were subjected to cardiac I/R.
  
  
  RESULTS
  Cardiac I/R injury aggravated brain oxidative stress, beta-amyloid production, and decreased dendritic spine density in either sham-operated or ovariectomized ND-fed rats, but not in ovariectomized HF-fed rats. Either estrogen or DPP-4 inhibitor therapies reduced those conditions in all rats with cardiac I/R.
  
  
  CONCLUSIONS
  Cardiac I/R aggravates brain toxicity in estrogen-deprived lean rats, but not in the estrogen-deprived obese rats. Estrogen and DPP-4 inhibitor treatments attenuate those effects in all groups.
authors.affiliation: 1Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center 2Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand 3School of Health Science, Mae Fah Luang University, Chiang Rai, Thailand 4Faculty of Life Sciences, The University of Manchester, Manchester, UK 5Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Wasana
authors.initials: W
authors.lastname: Pratchayasakul
authors.forename: Sivaporn
authors.initials: S
authors.lastname: Sivasinprasasn
authors.forename: Piangkwan
authors.initials: P
authors.lastname: Sa-Nguanmoo
authors.forename: Cicely
authors.initials: C
authors.lastname: Proctor
authors.forename: Sasiwan
authors.initials: S
authors.lastname: Kerdphoo
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
authors.forename: Siriporn C
authors.initials: SC
authors.lastname: Chattipakorn
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006321:Heart; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008593:Menopause / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000473:pathology; D010052:Ovariectomy / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D004967:Estrogens; D007004:Hypoglycemic Agents; D004958:Estradiol