Mahtab Farrokhi1, Mehdi Zekriyapanah Gashti2, Mahmood Hoormand3, Azam Bakhtiarian1, Rohalah Habibi4. 1. Department of Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 2. Department of Information Technology and Computer Science, Payame Noor University, Tehran, Iran. 3. Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: hoormand@gmail.com. 4. Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address: rhabibie@yahoo.com.
Abstract
PURPOSE: A potential therapeutic approach on skin flap necrosis is to target parallel pathways involved in necrosis. Azelaic Acid, Minoxidil and Caffeine combination was tried on skin flap survival by their possible interaction with ATP sensitive potassium (KATP) channels and nitric oxide pathway. MATERIAL AND METHODS: Sprauge-Dawley rats were divided into 8 groups for skin flap surgery. Azelaic acid, minoxidil, caffeine, or their combination were applied topically in different groups. Two additional groups were treated with L-NAME or glibenclamide in addition to the combination therapy. Percentage of flap necrosis was calculated and flap samples were removed to measure tissue malondialdehyde (MDA) and nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS), Bcl-2 and Bax proteins. RESULTS: Combination therapy profoundly decreased skin flap necrosis, tissue MDA contents, and expression of the pro-apoptotic protein Bax (p < 0.05 vs. single treatments). These effects were reversed by L-NAME and glibenclamide pre-treatments. Further evaluations showed combination therapy increases flap tissue NO content and iNOS expression (p < 0.05 vs. single treatments). CONCLUSION: Beneficial effect of the combination therapy with azelaic acid, minoxidil and caffeine therapy on rescuing the flap from necrosis by targeting parallel signaling pathways suggested potential applications in clinical practice.
PURPOSE: A potential therapeutic approach on skin flap necrosis is to target parallel pathways involved in necrosis. Azelaic Acid, Minoxidil and Caffeine combination was tried on skin flap survival by their possible interaction with ATP sensitive potassium (KATP) channels and nitric oxide pathway. MATERIAL AND METHODS: Sprauge-Dawley rats were divided into 8 groups for skin flap surgery. Azelaic acid, minoxidil, caffeine, or their combination were applied topically in different groups. Two additional groups were treated with L-NAME or glibenclamide in addition to the combination therapy. Percentage of flap necrosis was calculated and flap samples were removed to measure tissue malondialdehyde (MDA) and nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS), Bcl-2 and Bax proteins. RESULTS: Combination therapy profoundly decreased skin flap necrosis, tissue MDA contents, and expression of the pro-apoptotic protein Bax (p < 0.05 vs. single treatments). These effects were reversed by L-NAME and glibenclamide pre-treatments. Further evaluations showed combination therapy increases flap tissue NO content and iNOS expression (p < 0.05 vs. single treatments). CONCLUSION: Beneficial effect of the combination therapy with azelaic acid, minoxidil and caffeine therapy on rescuing the flap from necrosis by targeting parallel signaling pathways suggested potential applications in clinical practice.