Pentoxifylline Accelerates Gastric Ulcer Healing in Rats: Roles of Tumor Necrosis Factor Alpha and Neutrophils during the Early Phase of Ulcer Healing

Abstract

Background/Aims: Pentoxifylline has many anti-inflammatory properties including inhibition of production of tumor necrosis factor alpha (TNF-α). Although pentoxifylline prevents several types of gastric mucosal injury, the effect of this drug on ulcer healing is unknown. In this study, we examined the effect of pentoxifylline on healing of acetic acid induced gastric ulcers in rats. Methods: Rats with gastric ulcer received an intraperitoneal injection of 10 mg/kg pentoxifylline once daily for 14 days or for only the first 7 days or the last 7 days of the 14-day treatment period. Some rats were given antirat neutrophil antiserum intraperitoneally every other day. Ulcer size, myeloperoxidase activity, and concentration and location of TNF-α in ulcer tissue were assessed. Results: Administration of pentoxifylline for 14 days or for the first 7 days, but not for the last 7 days, of the 14-day treatment period accelerated ulcer healing. TNF-α was detected mainly in monocytes/macrophages and in some neutrophils at ulcer bases and margins. Pentoxifylline markedly decreased the concentration of TNF-α as well as the myeloperoxidase activity in ulcer tissue on days 2 and 4. Antirat neutrophil antiserum inhibited neutrophil infiltration into ulcer tissue and accelerated ulcer healing. Conclusion: Pentoxifylline accelerates healing of acetic acid induced gastric ulcer in rats. This effect may be due in part to reduction of neutrophil infiltration and inhibition of production of TNF-α by inflammatory cells. Early-phase inhibition of inflammatory response may accelerate ulcer healing.

Histological modification in TRAM flap in rats treated with pentoxifylline

“…The present work showed that pentoxifylline reduced necrosis in the caudal unipedicle TRAM flap in the rat, in accordance to previous works that utilized similar methods 6,13,18,20 , an evidence of the positive effect of this drug in reducing deleterious consequences of ischemia (Wilcoxon test, p=0.003).…”

“…Shimizu et al 13 showed that intraperitoneal administration of pentoxifylline, for 7 days in the preoperative period and in both preoperative (7 days) and postoperative (7 days) periods, were both efficient in improving viability in ischemic tissues. An explanation for the efficiency of the preoperative administration could be the 40 days erythrocytes half-life in young rats 19 .…”

“…An explanation for the efficiency of the preoperative administration could be the 40 days erythrocytes half-life in young rats 19 . Pentoxifylline does not have acute effects in erythrocytes' membranes, thus it is not effective when administered in the postoperative period alone 13,20 .…”

“…Thirty two Wistar-EPM rats were selected, at random, weighted (mean 300 g), kept in individual cages and kept without any alimentary restriction until study's day, when they were randomly separated in two groups: On the fifth postoperative day, the rats were anesthetized and the percentages of flaps' necrosis determined via the "paper template method" 13 …”

Evaluation of wound healing and antimicrobial properties of aqueous extract from Bowdichia virgilioides stem barks in mice

“…But, a long duration in the inflammatory phase causes a delay in healing process. Anti-inflammatory activity is necessary for shorten the healing period (Shimizu et al 2000). Therefore, the significant wound healing activity of AEBv may be related to its remarkable anti-inflammatory effect as presented in previous reports , Thomazzi et al 2010.…”