Wound healing activity of NOE-aspirin: a pre-clinical study.
Aspirin, one of the oldest non-steroidal anti-inflammatory drugs, impedes tissue repair by virtue of retarding inflammation. The present study was undertaken to find out if linking of nitrooxyethyl ester to aspirin reverses its healing-depressant propensity. Nitrooxyethyl ester of aspirin (NOE-Asp) was synthesized in our laboratory through well-established synthetic pathway, starting from aspirin through esterification with ethylene glycol and nitration with a mixture of nitric and sulfuric acids at 0 degrees C. The effect of NOE-Asp on phases of healing such as collagenation, wound contraction and epithelialization and on scar size of healed wound was evaluated in three wound models-incision, dead space, and excision wounds. To assess its influence on the oxidative stress, the levels of glutathione (GSH) and thiobarbiturate reactive species (TBARS) were also determined in 10-day-old granulation tissue. NOE-Asp was further screened for its anti-inflammatory activity in rat paw edema model. NOE-Asp promoted collagenation (increase in breaking strength, granulation weight, and collagen content), wound contraction, and epithelialization phases of healing. NOE-Asp also showed a significant antioxidant effect in 10-day-old granulation tissue as compared to aspirin. The results vindicate our assumption that the esterification of aspirin with nirooxyethyl group reverses the healing-suppressant effect of aspirin. The compound also showed equipotent anti-inflammatory activity as aspirin.
Kaushal
Mandeep
M
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal 576 104, India. kaushalman@hotmail.com <kaushalman@hotmail.com>
Gopalan Kutty
N
N
Mallikarjuna Rao
C
C
D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D017392:Thiobarbituric Acid Reactive Substances; D005978:Glutathione; D001241:Aspirin; D006909:Hydroxyproline