The effect of nitric oxide synthases inhibitors on inflammatory bowel disease in a rat model.
OBJECTIVE
Overexpression of nitric oxide (NO) has been implicated in the pathogenesis of experimental and clinical inflammatory bowel disease (IBD). NO is produced by two types of enzymes: constitutively expressed and inducible NO synthases (NOS). This study assessed N(W)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AMG), the most studied inhibitors of nitric oxide synthases, with regard to their effectiveness as modulators of inflammation in trinitrobenzene sulfonic acid (TNBS)-induced colitis in the rat.


METHODS
Colitis was induced in Wistar rats. The colitis was treated everyday for 10 days with L-NAME and AMG. To assess the severity of the colitis, clinical (body weight), hematological (hematocrit and erythrocytes sedimentation rate-ESR) and morphological (gross and microscopic) criteria were used.


RESULTS
The administration of both nitric oxide synthases inhibitors L-NAME and AMG proved to be beneficial in all the examined parameters compared with the control group. A statistically significant difference between the L-NAME and the AMG groups was observed only in macroscopic and histological grading.


CONCLUSIONS
NOS inhibitors may be promising agents in preventing the onset, or mediating the symptoms, of inflammatory bowel disease.
Pilichos
Charalambos J
CJ
Third Department of Propeudeutic Surgery, University of Athens, Sotiria Hospital, Athens, Greece.
Kouerinis
Ilias A
IA
Zografos
George C
GC
Korkolis
Dimiris P
DP
Preza
Athena A
AA
Gazouli
Maria
M
Menenakos
Evangelos I
EI
Loutsidis
Antonios E
AE
Zagouri
Flora
F
Gorgoulis
Vassilis G
VG
Fotiadis
Constantin I
CI
D000818:Animals; D001799:Blood Sedimentation; D001835:Body Weight / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006146:Guanidines / Q000627:therapeutic use*; D006400:Hematocrit; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D006146:Guanidines; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester