Protective effects of N(G)-nitro-L-arginine methyl ester and metallothioneins on excess nitric oxide toxicity in trinitrobenzene sulfonic acid-induced rat colitis.
OBJECTIVE
To evaluate the protective effects of N(G)-nitro-L-arginine methyl ester (L-NAME) and metallothioneins on excess nitric oxide toxicity in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis.


METHODS
In this study, 70 rats were assigned to 7 groups of controls, and colitis was induced with 120 mg/kg TNBS, 35 mg/kg L-NAME, and 1 and 2 mg/kg metallothionein 1 (MT1) and metallothionein 2 (MT2), respectively. A day after the administration of TNBS, L-NAME, MT1 and MT2 were given intraperitoneally for 3 days to the experimental groups. After the administration of TNBS, dissections of the rats in the L-NAME, MT1 and MT2 groups were performed at 3-day periods under ether anesthesia, and whole blood, bone marrow and colon were obtained.


RESULTS
On the third day, red and white blood cell values were increased, while platelet and bone marrow granule cells decreased in the L-NAME- and TNBS-induced group. On the third day, all the blood values increased in MT1 (1 and 2 mg/kg) and MT2 (1 and 2 mg/kg) in the TNBS-administered groups. Histologic findings were macroscopic score, ulcer, loss of mucous cells, crypt abscess, inflammatory cyst, mucosa atrophy, edema, vascular dilatation and induced nitric oxide synthetase, which increased in the descending colon in the colitis rats, while it was decreased rats given L-NAME, MT1 and MT2 administration.


CONCLUSIONS
The results suggest that MT1 and MT2 are more effective in protecting against the toxic effects of excess nitric oxide as compared with L-NAME in the colitis rats.
Altuner
Yilmaz
Y
Department of Biology, Faculty of Arts and Science, Eskişehir Osmangazi University, Eskişehir, Turkey.
Ayhanci
Adnan
A
Civi
Kismet
K
Ozden
Hilmi
H
Ustuner
Derya
D
Ustuner
M Cengiz
MC
Kurt
Hulyam
H
D000818:Animals; D001772:Blood Cell Count; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D014302:Trinitrobenzenesulfonic Acid; D008668:Metallothionein; D019331:NG-Nitroarginine Methyl Ester