Pentoxifylline attenuates mucosal damage in an experimental model of rat colitis by modulating tissue biomarkers of inflammation, oxidative stress, and fibrosis

Abstract

Background/aim: This study was designed to identify the effect of pentoxifylline on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.Materials and methods: Forty-two female Wistar rats were randomly divided into 7 groups: group A, TNBS + intraperitoneal (IP) pentoxifylline; group B, TNBS + IP saline; group C, TNBS + intrarectal (IR) pentoxifylline; group D, TNBS + IR saline; group E, IP pentoxifylline + TNBS; group F, IP saline + TNBS; group G, IR saline. Pentoxifylline was given daily for 3 days before or 6 days after the induction of colitis. Rats were killed after 6 days.Results: IP and IR pentoxifylline similarly and significantly reduced damage and histopathological scores. Pentoxifylline attenuated the accumulation of malonyldialdehyde and transforming growth factor β1 and the activities of myeloperoxidase, matrix metalloproteinase-3, and tissue inhibitor of metalloproteinases-1, and it also restored superoxide dismutase activity. The IP route was more effective than the IR route in this regard. Administration of IP pentoxifylline before or after induction did not influence all parameters.Conclusions: Pentoxifylline showed a therapeutic effect in this experimental colitis model. IP administration seemed to be better. This effect may occur as a result of inhibition of oxidative stress and metalloproteinase activity.

Natural Anti-Inflammatory Compounds as Drug Candidates for Inflammatory Bowel Disease

“…It is noteworthy that caffeine and theophylline also exert toxic effects. The suggested lethal dose of caffeine in the bloodstream is 80-100 mg/ml, which is reached by consuming approximately 10 g or higher of caffeine (Karatay et al, 2017).…”

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease

“…Experiments with rats suffering from ischemic colitis carried out by Reyhan et al (2014) showed that orally administered pentoxifylline (50 mg/kg of body weight) significantly downsizes the ischemic area and decreases colonic malondialdehyde (MDA) levels of the rats involved. Likewise, Karatay et al (2017) investigated the anti-colitis effect of pentoxifylline (100 mg/kg of body weight) on TNBS-induced colitis in rats and found that both intraperitoneal and intrarectal treatment of pentoxifylline could significantly reduce colonic injury by attenuating the accumulation of MDA and TGF-β1 and the activation of MPO, MMP-3, and MMP-1, thus restoring the activity of SOD. Such data indicates that the benefits of pentoxifylline on colitis might be partly mediated by inhibiting oxidative stress and metalloproteinase activities (Figure 4).…”

Development of an Advanced Multicellular Intestinal Model for Assessing Immunomodulatory Properties of Anti-Inflammatory Compounds

“…Plant-derived alkaloids have been shown to possess anti-inflammatory properties as demonstrated in animal models of disease, including inflammatory bowel disease (IBD), a group of disorders characterized by chronic inflammation of the gastrointestinal tract (Niu et al, 2013;Chen et al, 2017;Ruiz Castro et al, 2020). The positive effects of alkaloid have been linked to a modulation of intestinal oxidative stress (Karatay et al, 2017;Rodrigues de Carvalho et al, 2018), a strengthening of the epithelial barrier function (Zhang et al, 2017), and a boost of gut microbiota (Zhang et al, 2018).…”