PMID- 26202338
OWN - NLM
STAT- MEDLINE
DCOM- 20160909
LR  - 20181113
IS  - 1476-5489 (Electronic)
IS  - 0955-9930 (Linking)
VI  - 27
IP  - 5
DP  - 2015 Sep-Oct
TI  - Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory 
      markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat 
      (ZDF/fa/fa).
PG  - 182-90
LID - 10.1038/ijir.2015.13 [doi]
AB  - Oxidative stress and nitrosative stress present in type 2 diabetes mellitus 
      (T2DM) and metabolic syndrome (MS) induce inflammatory response in diverse 
      tissues including cavernous tissue (CT). Heat-shock proteins (HSPs) have an 
      important role in modulating and repairing tissue injury, although their 
      participation in CT in T2DM is unclear. Beyond the specific action of 
      phosphodiesterase type 5 inhibitors (PDE5i) on erectile function, it has been 
      proposed that chronic administration of these agents improves endothelial 
      function and ameliorates fibrotic changes. The aim of this study was to determine 
      in CT of Zucker Diabetic Fatty (ZDF) rat, an experimental model of T2DM and MS: 
      (1) the degree of oxidative stress and nitrosative stress; (2) the magnitude of 
      inflammatory markers such as tumor necrosis factor-alpha (TNFalpha) and interleukin 6 
      (IL6); (3) immunoexpression of HSP70 and HSP27; (4) how a long-term PDE5i 
      administration may modify these variables. For 6 months, (1) untreated ZDF; (2) 
      ZDF+Sildenafil (Sil) and (3) control Lean Zucker Rat (LZR) received no treatment, 
      were studied. Penises were processed for functional 'in vitro' studies, oxidative 
      and nitrosative stress evaluation and immunohistochemistry in CT using TNFalpha; IL6; 
      nitrotyrosine, HSP70 and HSP27 antibodies. ZDF+Sil presented better relaxation in 
      corporal strips versus untreated ZDF. Furthermore, ZDF+Sil presented less 
      lipoperoxidation in CT versus untreated ZDF. The activity of antioxidant enzymes 
      CuZn superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPx) was also 
      reduced in untreated ZDF in CT along with a decrease in glutathione versus 
      untreated ZDF. Nitrotyrosine expression was increased in untreated-ZDF rats 
      versus ZDF+Sil and LZR. TNFalpha and IL6 were decreased in CT in ZDF+Sil versus 
      untreated ZDF. Additionally, the expression of HSP70 and HSP27 was reduced in CT 
      in ZDF+Sil versus untreated ZDF. In conclusion, this study provides substantial 
      evidence supporting a protective role of a long-term therapy with Sil on CT in a 
      recognized animal model of T2DM and MS.
FAU - Toblli, J E
AU  - Toblli JE
AD  - Laboratory of Experimental Medicine, Hospital Aleman, School of Medicine, 
      University of Buenos Aires, Buenos Aires, Argentina.
FAU - Cao, G
AU  - Cao G
AD  - Laboratory of Experimental Medicine, Hospital Aleman, School of Medicine, 
      University of Buenos Aires, Buenos Aires, Argentina.
FAU - Angerosa, M
AU  - Angerosa M
AD  - Laboratory of Experimental Medicine, Hospital Aleman, School of Medicine, 
      University of Buenos Aires, Buenos Aires, Argentina.
FAU - Rivero, M
AU  - Rivero M
AD  - Laboratory of Experimental Medicine, Hospital Aleman, School of Medicine, 
      University of Buenos Aires, Buenos Aires, Argentina.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150723
PL  - England
TA  - Int J Impot Res
JT  - International journal of impotence research
JID - 9007383
RN  - 0 (Biomarkers)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Diabetes Mellitus, Type 2/metabolism
MH  - Heat-Shock Proteins/*metabolism
MH  - Inflammation/*metabolism
MH  - Male
MH  - Oxidative Stress/drug effects
MH  - Penis/*drug effects/metabolism
MH  - Phosphodiesterase 5 Inhibitors/*pharmacology
MH  - Rats
MH  - Rats, Zucker
EDAT- 2015/07/24 06:00
MHDA- 2016/09/10 06:00
CRDT- 2015/07/24 06:00
PHST- 2014/10/12 00:00 [received]
PHST- 2015/04/10 00:00 [revised]
PHST- 2015/06/09 00:00 [accepted]
PHST- 2015/07/24 06:00 [entrez]
PHST- 2015/07/24 06:00 [pubmed]
PHST- 2016/09/10 06:00 [medline]
AID - ijir201513 [pii]
AID - 10.1038/ijir.2015.13 [doi]
PST - ppublish
SO  - Int J Impot Res. 2015 Sep-Oct;27(5):182-90. doi: 10.1038/ijir.2015.13. Epub 2015 
      Jul 23.