Mitigation of indomethacin-induced gastric mucosal lesions by a potent specific type V phosphodiesterase inhibitor.
OBJECTIVE
To investigate the gastroprotective effect of vardenafil against indomethacin-induced gastric damage.


METHODS
Forty-eight female Wistar albino rats were randomly divided into 6 groups. Group 1 received saline only. Group 2 (indomethacin) received indomethacin. Rats in group 3 and 4 were pretreated with different doses of famotidine. Group 5 and 6 were pretreated with different doses of vardenafil. Rats in groups 3 to 6 received 25 mg/kg indomethacin 30 min after pretreatment. The animals were sacrificed 6 h later and their stomachs were opened. Gastric lesions were counted and measured. The stomach of each animal was divided in two parts for histopathological examinations and nitric oxide (NO) and malondialdehyde (MDA) assays, respectively.


RESULTS
There were no gastric mucosal lesion in the saline group but all rats in the indomethacin group had gastric mucosal ulcerations (ulcer count; 6.25 +/- 3.49, and mean ulcer area; 21.00 +/- 12.35). Ulcer counts were diminished with famotidine 5 mg/kg (4.12 +/- 2.47, P > 0.05), 20 mg/kg (2.37 +/- 4.43, P < 0.05), vardenafil 2 mg/kg (4.37 +/- 3.06), and vardenafil 10 mg/kg (1.25 +/- 1.38, P < 0.05) compared to the indomethacin group. Gastric mucosal lesion areas were diminished with famotidine 5 mg/kg (8.62 +/- 2.97, P < 0.001) , famotidine 20 mg/kg (0.94 +/- 2.06, P < 0.001), vardenafil 2 mg/kg (6.62 +/- 5.87, P < 0.001), and vardenafil 10 mg/kg (0.75 +/- 0.88, P < 0.001) compared to the indomethacin group. MDA levels were significantly higher in indomethacin group (28.48 +/- 14.51), compared to the famotidine 5 mg/kg (6,21 +/- 1.88, P < 0.05), famotidine 20 mg/kg (5.88 +/- 1.60. P < 0.05), vardenafil 2 mg/kg (15.87 +/- 3.93, P < 0.05), and vardenafil 10 mg/kg (10.97 +/- 4.50, P < 0.05). NO concentration in gastric tissues of the famotidine groups were significantly increased (P < 0.05), but the NO increases in the vardenafil groups were not statistically significant. Histopathology revealed diminished gastric damage for pretreatment groups compared to the indomethacin group (P < 0.05).


CONCLUSIONS
Vardenafil affords a significant dose-dependent protection against indomethacin induced gastric mucosal lesions in rats.
Karakaya
Kemal
K
Department of General Surgery, Zonguldak Karaelmas University, Medical Faculty, 67600 Kozlu, Zonguldak, Turkey. karakayakemal@hotmail.com
Hanci
Volkan
V
Bektas
Sibel
S
Can
Murat
M
Ucan
Hamdi-B
HB
Emre
Ali-Ugur
AU
Tascilar
Oge
O
Ozkocak Turan
Isil
I
Comert
Mustafa
M
Irkorucu
Oktay
O
Karadeniz Cakmak
Guldeniz
G
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D015738:Famotidine / Q000627:therapeutic use; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007213:Indomethacin / Q000009:adverse effects*; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D018384:Oxidative Stress; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013450:Sulfones / Q000627:therapeutic use; D014227:Triazines / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D009569:Nitric Oxide; D008315:Malondialdehyde; D000069058:Vardenafil Dihydrochloride; D015738:Famotidine; D007213:Indomethacin