The anti-inflammatory effects of the phosphodiesterase inhibitor pentoxifylline in the rat.
The present study aimed to evaluate the anti-inflammatory effects of pentoxifylline (PTX), a non-specific phosphodiesterase inhibitor in the rat. Acute inflammation was induced by subplantar injection of carrageenan (1%) in the rat hind paw. Results showed that intraperitoneal (i.p.) administration of PTX (36 or 72 mg kg(-1)) 30 min prior to carrageenan reduced the paw oedema response in dose-dependent manner with a maximal effect of 18.9 and 40.1%, respectively, at 2h post-carrageenan (P<0.001 and <0.001 at respective doses). Theophylline given at equimolar doses (29.9 or 45.8 mg kg(-1), i.p.) did not reduce the oedema response. With higher doses of PTX (144-300 mg kg(-1), i.p.) the anti-oedema effect of the drug was more pronounced, but mainly confined to the first 2h following carrageenan injection and decreasing rapidly thereafter. PTX (72 mg kg(-1), i.p.) given 30 min after carrageenan challenge reduced the oedema response by 24.7 and 26.2% at 1 and 2h after dosing (P<0.05 and <0.05, respectively). PTX (36 or 72 mg kg(-1), i.p.) co-administered with indomethacin (5 mg kg(-1), i.p.) 30 min before carrageenan had little modulatory effect on the anti-oedema effect of indomethacin, but the higher dose of PTX (144 mg kg(-1), i.p.) reduced the anti-inflammatory effect of indomethacin by 24% at 4h post-carrageenan. PTX (72 mg kg(-1), i.p.) enhanced the anti-oedema effect of the selective COX-2 inhibitor celecoxib (33 mg kg(-1), i.p.) by 55.1% at 4h post-carrageenan. In contrast, the higher dose of PTX (144 mg kg(-1), i.p.) reduced the anti-oedema effect of celecoxib by 46.8% at 4h post-carrageenan. PTX (36 or 72 mg kg(-1)) enhanced the anti-oedema effect of dexamethasone (0.1 mg kg(-1)) with maximal effect of 76 and 104.8% at 2h post-carrageenan (P<0.01 and <0.01 for respective doses). PTX (0.6 mg per paw) given with carrageenan into the rat hind paw reduced the oedema response with a maximal effect of 33.4% at 1h following carrageenan. PTX (0.6 mg per paw) given in the contralateral hind paw reduced the carrageenan-induced paw oedema for 1h by 32.2%. Thus, PTX, when given at doses comparable to those used in man for treatment of circulatory disorders displayed anti-inflammatory in vivo and enhanced the anti-inflammatory effect of a selective COX-2 inhibitor or dexamethasone. PTX may have therapeutic potential as anti-inflammatory agent either alone or in combination with non-steroidal anti-inflammatory drugs or with steroids. There is also an intriguing possibility for the use of topical preparations for the management of local inflammatory conditions.
Abdel-Salam
Omar M E
OM
Department of Pharmacology, National Research Centre, Tahrir Street, Dokki, Cairo, Egypt. omasalam@hotmail.com
Baiuomy
Ayman R
AR
El-Shenawy
Siham M
SM
Arbid
Mahmoud S
MS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002351:Carrageenan; D000068579:Celecoxib; D003907:Dexamethasone / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D007213:Indomethacin / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D010431:Pentoxifylline / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D010726:Phosphodiesterase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D003907:Dexamethasone; D002351:Carrageenan; D000068579:Celecoxib; D010431:Pentoxifylline; D007213:Indomethacin