Effect of melatonin in rectal suppositories on oxidative stress parameters in TNBS-induced colitis

Oxidative stress is a key component in the pathogenesis of inflammatory bowel diseas. Melatonin is an endogenous regulator of homeostasis with pleiotropic properties, including antioxidant effects; rectal formulations of melatonin are not registered in the Russian Federation. The aim of research was to study the effect of melatonin incorporated into original rectal suppositories on oxidative stress parameters in experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS colitis). Sixty-four Wistar rats were divided into four groups: intact; TNBS colitis; TNBS colitis + rectal suppositories with melatonin; TNBS colitis + rectal suppositories without active component (placebo). The TNBS colitis model was reproduced by weekly rectal administration of TNBS in increasing doses (15–60 mg/kg) for 6 weeks. The disease activity index, fecal calprotectin concentration, levels of lipid peroxidation products, and total antioxidant status in the colonic mucosa at the site of injury were assessed. The TNBS colitis model in rats reproduces clinical and laboratory manifestations of inflammatory bowel disease. It was found that the use of rectal suppositories with melatonin in TNBS colitis led to a decrease in disease activity index and fecal calprotectin concentration, a decrease in the content of lipid peroxidation products, and an increase in total antioxidant status compared with the TNBS colitis and TNBS colitis groups with rectal suppositories without an active component. The obtained data demonstrate the efficacy of melatonin in rectal suppositories in TNBS colitis and provide a rationale for further studies, as well as for the potential use of melatonin–containing rectal suppositories as part of combination therapy for inflammatory bowel disease.

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