ABSTRACT
ABSTRACT Purpose To investigate the efficacy of cordycepin, an adenosine analogue, on prevention of esophageal damage and stricture formation due to esophageal caustic burns in rat model comparing with prednisolone. Methods Caustic esophageal burn was introduced by 37.5% of NaOH to distal esophagus. Thirty-two Wistar albino rats were divided in four groups: sham rats undergone laparotomy, treated with 0.9% NaCl; control rats injured with NaOH without cordycepin treatment; cordycepin group injured with NaOH, treated with 20 mg/kg cordycepin; prednisolone group injured with NaOH, treated with 1 mg/kg prednisolone for 28 days. Efficacy was assessed by histopathological and immunohistochemical analysis of esophageal tissues. Results Cordycepin treatment significantly decreased inflammation, granulation tissue and fibrous tissue formation and prevented formation of esophageal strictures shown by histopathological damage score and stenosis indexes compared to control group (p < 0.01). These effects are relatively more substantial than prednisolone, probably based on attenuation of elevation of proinflammatory cytokines hypoxia-inducible factor 1-alpha (HIF-1?), tumor necrosis factor alpha (TNF-?), proliferative and fibrotic factor fibroblast growth factor 2 (FGF2) and angiogenic factor vascular endothelial growth factor A (VEGFA) (p < 0.05). Conclusions The findings suggest that cordycepin has a complex multifactorial healing process in alkali-burned tissue, more successful than prednisolone in preventing the formation of esophageal strictures and may be used as a therapeutic agent in the acute phase of esophageal alkali-burn.
Subject(s)
Animals , Rats , Burns, Chemical/drug therapy , Caustics/toxicity , Caustics/therapeutic use , Esophageal Stenosis/chemically induced , Esophageal Stenosis/prevention & control , Esophageal Stenosis/drug therapy , Deoxyadenosines , Rats, Wistar , Vascular Endothelial Growth Factor A/therapeutic use , Alkalies/therapeutic use , Anti-Inflammatory Agents/therapeutic useABSTRACT
Abstract Purpose To examine the therapeutic effect of external adenosine on an acetic acid-induced acute ulcerative colitis model in rats. Methods Thirty male mature rats were divided into three groups as control, acute colitis (AC) and AC+adenosine group (AC+AD). AC was induced by rectal administration of 4% acetic acid (AA). 5mg/kg/day adenosine was performed i.p for 4 weeks to AC+AD group. Rectum and colon were excised for microscopic and histopathological histopathologic evaluations, and immunohistochemical analysis of nuclear factor kappa B (NF-kB). Blood samples were collected for biochemical detection of TNF-α, Pentraxin-3 and malondialdehyde (MDA) levels. Results AC group had generalized hyperemia and hemorrhage with increased macroscopic and histopathological scores compared with control (P <0.0001) while adenosine treatment decreased these scores significantly (P <0.001), with reduced distribution of disrupted epithelium, leukocyte infiltrates, and focal hemorrhage. AC group showed significantly increased immunoexpression of NF-kB in rectum, plasma and tissue levels of TNF-α, plasma Pentraxin-3 and MDA levels (P <0.0001) while adenosine reduced these levels (P < 0.05). Conclusion Adenosine appears to promote healing of colon and rectum exposed to AA-induced AC, suggesting a boosting effect of adenosine on the intestinal immune system to cure ulcerative colitis.
Subject(s)
Animals , Male , Colitis, Ulcerative/drug therapy , Adenosine/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Rectum/pathology , Reference Values , Time Factors , C-Reactive Protein/analysis , Serum Amyloid P-Component/analysis , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/pathology , Acute Disease , Reproducibility of Results , NF-kappa B/analysis , Tumor Necrosis Factor-alpha/analysis , Treatment Outcome , Thiobarbituric Acid Reactive Substances , Rats, Sprague-Dawley , Colon/pathology , Acetic Acid , Malondialdehyde/bloodABSTRACT
Abstract Purpose: To investigate the prophylactic and therapeutical effects of sildenafil in a model of acute radiation proctitis (ARP). Methods: All experimental procedures of this study was examined by histopathological, immunohistochemical and transmission electron microscopic analysis. Results: Our histopathological evaluations indicated significant increases in lesion severity, cryptic apsis, cryptitis, cryptic distortion, reactive atypia and infiltration depth of the control (proctitis) group. While the prophylaxis group and the treatment group had significantly lower scores. High-dose group showed similar results as prophylaxis group. Histopathological findings of the prophylaxis group was more significant than the treatment group. Immunoreactivities of IL-1β, FGF-2, TNF- α and HIF-1α increased in the control group especially in the epithelial and cryptic regions. On the contrary, sildenafil application caused significant decreases of inflammatory markers in all treatment groups, specifically better results in the prophylaxis group. Conclusion: The sildenafil has anti-inflammatory effects on ARP, as well as protective effects against ARP and the protective effect of sildenafil surpasses its therapeutic effect histopathologically.