Change of nitric oxide in experimental colitis and its inhibition by melatonin in vivo and in vitro

Abstract

Aim: 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. Conclusion: This study showed that TNBS/ethanol induced colitis was pharmacologically controlled by melatonin in vivo and in vitro.

The Effect of Hypericum perforatum (St. John’s Wort) on Experimental Colitis in Rat

“…Mei and co-workers showed that colon inflammation between days 7 and 28 was associated with increased production of NO, and melatonin treatment suppressed the increase of NO; thus the extent of colonic inflammation was inhibited and colon mucosa injury was prevented [30]. These results are compatible with our study.…”

“…For this reason, MPO activity is expected to be high in colon. In our study, MPO activity increased in colitis groups, consistent with previous studies [24,25,[28][29][30][31], and MPO levels were slightly decreased in treated groups, although this decrease was not statistically significant.…”

“…NO level was normal on the seventh day. It has been suggested that increased NO synthesis by inducible nitric oxide synthase (iNOS) in inflamed colon may play a role in aggravation of inflammation and tissue injury [30]. Hypericum inhibits both iNOS and cyclooxygenase-2 (COX-2) expression.…”

Investigation of the effect of intracolonic melatonin gel formulation on acetic acid-induced colitis

“…Both intracolonic melatonin gel formulation and IP administration of melatonin decreased the levels of NOx in colon cells, and it is known that melatonin administration inhibits NOx levels due to its antioxidant properties. Our results showed similarity with the results of previously conducted studies (Mei et al, 2005).…”

“…In studies evaluating the antioxidant efficacy, melatonin with an isotonic saline solution has been administered either intracolonically or through the IP route (Cuzzocrea et al, 2001;Mei et al, 2005;Marquez et al, 2006;Necefli et al, 2006;Nosál'ova et al, 2007). To our knowledge, no in vitro or in vivo intracolonic formulation study has been performed with melatonin.…”