Mebendazole, an anti-helminth drug, suppresses inflammation, oxidative stress and injury in a mouse model of ulcerative colitis

Abstract

Mebendazole (MBZ) is an efficacious anthelmintic with known anti-inflammatory and fibrinolytic properties. In this study, we aimed to explore the protective effects of this FDA-approved drug against DSS-induced colitis in a murine model either alone or in combination with Sulfasalazine (SSZ), a standard therapy for ulcerative colitis. We found that MBZ significantly improved colitis disease activity index as assessed by changes in body weight, degree of stool consistency, rectal bleeding, and prolapse. We also found that MBZ ameliorated the colon histopathological score by attenuating crypt loss, mucosal damage, and inflammation score in colitis tissues. Similarly, DSS-induced colon shortening, colon weight loss, and increase in spleen weight were all abrogated in the presence of MBZ. Moreover, MBZ decreased inflammation, possibly by reducing oxidative stress markers, suppressing inflammatory cell infiltration, and down-regulation of inflammatory genes in colon tissues. Furthermore, MBZ potently reduced fibrosis by decreasing collagen deposition and down-regulating pro-fibrotic genes including Col 1a1 and Col 1a2 in colitis tissue homogenates. In conclusion, our study showed that this broad-spectrum anthelminthic could be repurposed as a novel therapy for ulcerative colitis without any observed side effects, however, regarding the concerns about the potential toxicity of MBZ in UC patients, future experiments on MBZ therapy in other models of UC is needed to completely address the toxicity concerns.

The Role of Dietary Habits in the Pathogenesis and Development of Inflammatory Bowel Disease: A Narrative Review

“…Therefore, the basic principle of the dysregulated immune system following consumption and the UC is proven in the study, which assessed the relationship between oral mebendazole and the mucus layer composition. 25 …”

Anti-inflammatory and Ameliorative effects of two newly isolated probiotic strains in DSS-induced mouse model of colitis

“…Concentrations of oxidative stress markers including malonyl dialdehyde (MDA), and the enzymatic activity of superoxide dismutase (SOD) were measured in colon tissue samples as described previously (25).…”

“…Total RNA was extracted from homogenized colon tissue samples and complementary DNA (cDNA) was synthesized according to the manufacturer's instructions. Quantitative real-time polymerase chain reaction (RT-PCR) was performed by using the Amplicon SYBR Green PCR Master Mix as previously described (25). The sequence of primers are listed in Table 7.…”

Could Dicrocoelium dendriticum eggs play a potential immunotherapeutic role experimental colitis?

“…From the time of DSS induction, mice in order to control weight loss, rectal prolapse, stool consistency and rectal bleeding, were screened daily and data were recorded. And nally, we evaluate the in ammation according to the disease activity index (DIA) (IBD) which includes 4 variables described in Table 1 (24). On the 10th day, after seeing the clinical signs all mice were killed in accordance with animal rights and the intestines of mice were removed for cytokine and histopathological assays.…”