Change of nitric oxide in experimental colitis and its inhibition by melatonin in vivo and in vitro.
OBJECTIVE
To investigate the change of nitric oxide (NO) in rat colitis and its inhibition by melatonin in vivo and in vitro.


METHODS
In vivo, rat colitis was established intracolonically with trinitrobenzenesulphonic acid (TNBS) and ethanol. The animals were randomised into five groups: control group, model group, melatonin group (2.5, 5.0, 10.0 mg/kg), and treated intracolonically with saline, saline and melatonin respectively (once a day, from day 7 after colitis was established to day 28). After the end of the experiment, the mucosal damage index (CMDI) and histology score (HS) were evaluated and the level of myeloperoxidase (MPO) and malondiadehyde (MDA) and NO in the colon tissue were measured. In vitro, the co-culture model of the inflamed colon mucosa (from the colitis) with lipopolysaccharide (LPS), and the colonocytes oxidative injury model by hydroxyl radical, were designed respectively to elucidate the inhibition of NO by melatonin.


RESULTS
After treated with TNBS/ethanol, the extent of CMDI and HS, the levels of MPO, MDA, and NO in the model group, were higher than that in the control group; melatonin ameliorated these parameters effectively. The stimulation of LPS increased the level of NO and MPO and MDA in the co-culture model of inflamed colon mucosa, and melatonin significantly reduced the level of MPO, MDA, and NO. In the coloncyte oxidative injury model by hydroxyl radical, the contents of LDH, MDA, and NO were increased; melatonin reversed this oxidative injury considerably.


CONCLUSIONS
This study showed that TNBS/ethanol induced colitis was pharmacologically controlled by melatonin in vivo and in vitro.
Mei
Q
Q
Digestive Department, The First Affiliated Hospital, Anhui Medical University, Hefei, China.
Xu
J-M
JM
Xiang
L
L
Hu
Y-M
YM
Hu
X-P
XP
Xu
Z-W
ZW
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid
D016166:Free Radical Scavengers; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D008315:Malondialdehyde; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D008550:Melatonin