Pentoxifylline accelerates gastric ulcer healing in rats: roles of tumor necrosis factor alpha and neutrophils during the early phase of ulcer healing.
OBJECTIVE
Pentoxifylline has many anti-inflammatory properties including inhibition of production of tumor necrosis factor alpha (TNF-alpha). 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-alpha 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-alpha was detected mainly in monocytes/macrophages and in some neutrophils at ulcer bases and margins. Pentoxifylline markedly decreased the concentration of TNF-alpha 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.


CONCLUSIONS
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-alpha by inflammatory cells. Early-phase inhibition of inflammatory response may accelerate ulcer healing.
Shimizu
N
N
3rd Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.
Watanabe
T
T
Arakawa
T
T
Fujiwara
Y
Y
Higuchi
K
K
Kuroki
T
T
D019342:Acetic Acid; D000704:Analysis of Variance; D000818:Animals; D006401:Hematologic Agents / Q000627:therapeutic use*; D007124:Immunoenzyme Techniques; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010431:Pentoxifylline / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*; D014945:Wound Healing / Q000187:drug effects*
D006401:Hematologic Agents; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D019342:Acetic Acid; D010431:Pentoxifylline