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.

Study Design: 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.

Conclusion: 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.