Abstract
Antibiotic treatment increases susceptibility to development of inflammatory bowel diseases (IBD) both in children and adults. Oxidative stress plays a prominent role in IBD pathogenesis. The aim of present study was to test an interrelationship between the morphological changes in rat colonic mucosa, the levels of antioxidant enzymes and redox sensitive transcription factors Egr-1 and Sp-1 after treatment with cephalosporin antibiotic ceftriaxone (Cf) with broad spectrum of action. Study was performed on male Wistar rats (180–230 g). Cf (50 mg/kg, i.m.) were injected daily for 5 days. The colonic levels of catalase and superoxide dismutase activity were measured by the colorimetric assays and zymography; levels of Egr-1 and Sp-1 – by Western-blot analysis; histological changes – by morphometric analysis. Body weight and diarrhea were recorded. Systemic administration of the ceftriaxone induced morphological and functional changes in rat colonic mucosa associated with initial stages of the acute inflammation. These changes were accompanied by a decrease of activity of superoxide dismutase and catalase. Levels of redox-sensitive transcription factors Egr-1 and Sp1 were significantly increased, which shows a disturbance of homeostasis of the intestinal barrier. Keywords: ceftriaxone, colon, antioxidants, transcription factors.
Highlights
The inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn’s disease are characterized by chronic non-specific inflammation and ulcers of the intestinal mucosa of unknown etiology
We did not detect a significant difference in body loss between control and antibiotic-treated rats
The morphometric analysis of histological sections of rat colon revealed that 5 days of ceftriaxone administration increased the thickness of the mucous membrane, the depth of intestinal crypts, and the area of the colonocytes nuclei
Summary
The inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn’s disease are characterized by chronic non-specific inflammation and ulcers of the intestinal mucosa of unknown etiology. In 2011, two independent groups reported about positive correlation between longterm use of antibiotics and the risk of IBD in children [2] and adults (average age – 43.4 years) [12]. The mechanisms underlying this phenomenon are hypothetical and require empirical study. A disruption of the intestinal barrier function is a crucial factor for the IBD pathoge nesis [3]. We have found that a disruption of the intestinal barrier integrity at early stages
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