nifuroxazide and Colitis--Ulcerative

Nifuroxazide (NFX) is a safe nitrofuran antibacterial drug used clinically to treat acute diarrhea and infectious traveler diarrhea or colitis. Recent studies revealed that NFX displays multiple pharmacological effects, including anticancer, antioxidant, and anti-inflammatory effects. NFX has potential roles in inhibiting thyroid, breast, lung, bladder, liver, and colon cancers and osteosarcoma, melanoma, and others mediated by suppressing STAT3 as well as ALDH1, MMP2, MMP9, Bcl2 and upregulating Bax. Moreover, it has promising effects against sepsis-induced organ injury, hepatic disorders, diabetic nephropathy, ulcerative colitis, and immune disorders. These promising effects appear to be mediated by suppressing STAT3 as well as NF-κB, TLR4, and β-catenin expressions and effectively decreasing downstream cytokines TNF-α, IL-1β, and IL-6. Our review summarizes the available studies on the molecular biological mechanisms of NFX in cancer and other diseases and it is recommended to translate the studies in experimental animals and cultured cells and repurpose NFX in various diseases for scientific evidence based on human studies.

Topics: Animals; Colitis, Ulcerative; Diarrhea; Humans; NF-kappa B; Nitrofurans; Signal Transduction; Travel

Ulcerative colitis (UC) is a common intestinal problem characterized by the diffusion of colon inflammation and immunity dysregulation. Nifuroxazide, a potent STAT-3 inhibitor, exhibits diverse pharmacological properties. The present study aimed to elucidate a novel anti-colitis mechanism of nifuroxazide against the acetic acid-induced UC model.. Rats were grouped into control (received vehicle), UC (2 ml of 5% acetic acid by intrarectal infusion), UC plus sulfasalazine (100 mg/kg/day, P.O.), UC plus nifuroxazide (25 mg/kg/day, P.O.), and UC plus nifuroxazide (50 mg/kg/day, P.O.) and lasted for 6 days.. The present study revealed that nifuroxazide significantly reduced UC measures, hematological changes, and histological alteration. In addition, treatment with nifuroxazide significantly down-regulated serum CRP as well as the colonic expressions of MPO, IL-6, TNF-α, TLR-4, NF-κB-p65, JAK1, STAT-3, DKK1 in a dose-dependent manner. Besides, our results showed that the colonic Wnt expression was up-regulated with nifuroxazide treatment. In a dose-dependent manner, nifuroxazide markedly alleviated acetic acid-induced cellular infiltration and improved ulcer healing by increasing intestinal epithelial cell regeneration.. Our results collectively indicate that nifuroxazide is an effective anti-colitis agent through regulation of colon inflammation and proliferation via modulation IL-6/STAT-3/Wnt signaling pathway.

Topics: Acetic Acid; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Colitis, Ulcerative; Disease Models, Animal; Gene Expression Regulation; Hydroxybenzoates; Interleukin-6; Male; Nitrofurans; Rats; Rats, Wistar; STAT3 Transcription Factor; Wnt1 Protein

Ulcerative colitis (UC) is a disease of increased worldwide prevalence. UC progression is associated with serious complications that leave the patient with considerable health burdens. Nifuroxazide is an oral nitrofuran antibiotic used as antidiarrheal medication. The current study places an emphasis on investigating the potential therapeutic effectiveness of nifuroxazide (10 mg/kg) and (20 mg/kg) against acetic acid (AA)-induced UC. Intra-rectal AA induced a significant colonic injury and impairment of colonic biochemical and functional incidences. Nifuroxazide in a dose-dependent manner significantly corrected UC associated injury. Macroscopic scoring of UC, serum lactate dehydrogenase (LDH) activity, C-reactive protein (CRP) titer, colon malondialdehyde (MDA) and total nitric oxide (NOx) contents significantly declined. Meanwhile, serum total antioxidant capacity (TAC) and colon catalase, superoxide dismutase (SOD) and glutathione transferase (GST) activities and reduced glutathione (GSH) concentration significantly increased in a dose-dependent way. Ultimately, histopathological, immunohistochemical and ultramicroscopic analysis of colon specimen revealed significant improvement. To pinpoint the mechanistic pathway underlying the curative effect of nifuroxazide, colon expression of NF-κB, caspase-3 was evaluated along with STAT-3 activation. Nifuroxazide induced a dose-dependent significant suppression of NF-κB and caspase-3 signaling together with STAT3 signaling. In conclusion; nifuroxazide can be proposed as a therapeutic candidate to attenuate UC and its associated symptoms. The potential underlying mechanism involves suppression of NF-κB/STAT-3/caspase- signaling.

Topics: Acetic Acid; Animals; Anti-Bacterial Agents; Antidiarrheals; Colitis, Ulcerative; Colon; Hydroxybenzoates; Male; NF-kappa B; Nitrofurans; Rats, Wistar; Signal Transduction; STAT3 Transcription Factor