The effects of sildenafil citrate on ischemic colonic anastomotic healing in rats: its relationship between nitric oxide and oxidative stress.
BACKGROUND
The purpose of this study was to examine the effects of sildenafil citrate on normal and ischemic colon anastomosis in the rat model by measuring the levels of blood and colonic tissues nitric oxide, thiobarbituric acid reactive substrates (as a marker of lipid peroxidation), and glutathione (as an antioxidant).


METHODS
Normal (group 1 and 3) and ischemic anastomosis (group 2 and 4) were performed in four equal rat groups (n = 14). Orally 10 mg/kg per day of sildenafil citrate therapy were applied in group 3 and group 4 after operation. Seven rats of the each group were killed on postoperative days 3 and 7.


RESULTS
Sildenafil citrate therapy was resulted in elevated nitric oxide levels in both normal and ischemic anastomotic tissues (p < 0.0001 and p < 0.03) at postoperative day 3. Tissue thiobarbituric acid reactive substrate levels were elevated in rats with normal anastomosis by sildenafil therapy (p < 0.001) at postoperative days 3 and 7 (p < 0.05). Sildenafil therapy given to the normal anastomosis group has significantly higher tissue nitric oxide levels than the normal anastomosis group without therapy at postoperative day 7 (p < 0.001). On postoperative day 7, plasma nitric oxide levels were decreased by sildenafil citrate in rats with normal (p < 0.01) and ischemic anastomosis (p < 0.05). The beneficial effect of sildenafil citrate also was seen for erythrocyte glutathione levels in rats with normal anastomosis at postoperative day 7 and in rats with ischemic anastomosis at postoperative day 3.


CONCLUSIONS
Our results suggest that sildenafil citrate may affect ischemic anastomotic healing due to its possible effects on nitric oxide metabolism and lipid peroxidation. However, functional implication of this agent further needs to be elucidated.
Uzun
Hafize
H
Department of Biochemistry, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. huzun59@hotmail.com
Konukoglu
D
D
Nuri
M K
MK
Ersoy
E Y
EY
Ozçevik
S
S
Yavuz
N
N
D000714:Anastomosis, Surgical; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003106:Colon / Q000098:blood supply* / Q000187:drug effects / Q000601:surgery*; D005978:Glutathione / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D018709:Statistics, Nonparametric; D013450:Sulfones / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D015415:Biomarkers; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D005978:Glutathione