Shayandokht Taleb1, Peiman Moghaddas2, Maryam Rahimi Balaei2, Shabnam Taleb2, Sina Rahimpour2, Ata Abbasi3, Shahram Ejtemaei-Mehr2, Ahmad Reza Dehpour4. 1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 4. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpour@yahoo.com.
Abstract
BACKGROUND: Metformin has shown cardioprotective effects in experimental models of ischemia reperfusion, which is partially mediated through nitric oxide (NO) synthesis. We investigated the effects of metformin pretreatment in a rat model of random-pattern skin flap, and the probable role of NO system. MATERIALS AND METHODS: In the first experiment, the rats received increasing doses of metformin (150, 200, and 300 mg/kg), 4 h before the procedure. Dorsal skin flaps with caudal pedicles were elevated at the midline and flap survival was measured 7 d after surgery. Pathologic review of the skin flap specimen was performed in a subset of animals. In the second experiment, for evaluation of the role of NO, an NO synthase inhibitor N-nitro-L-arginine methyl ester hydrochloride (L-NAME) was administered with and without the effective dose of metformin. In the next experiment, subtherapeutic dose of NO precursor, L-Arginine, was administered with and without subeffective dose of metformin. RESULTS: Metformin pretreatment at doses of 200 and 300 mg/kg significantly increased skin flap survival rate. However, administration of L-NAME abolished the protective effects of metformin. On the other hand, subtherapeutic dose of L-arginine augmented the effects of low-dose metformin and significantly increased skin flap survival. Skin flaps from those rats that received 300 mg/kg metformin pretreatment and those treated with subtherapeutic doses of L-arginine and metformin showed increased vasodilation compared with control group. CONCLUSIONS: Metformin pretreatment can improve skin flap survival through an NO dependent pathway.
BACKGROUND:Metformin has shown cardioprotective effects in experimental models of ischemia reperfusion, which is partially mediated through nitric oxide (NO) synthesis. We investigated the effects of metformin pretreatment in a rat model of random-pattern skin flap, and the probable role of NO system. MATERIALS AND METHODS: In the first experiment, the rats received increasing doses of metformin (150, 200, and 300 mg/kg), 4 h before the procedure. Dorsal skin flaps with caudal pedicles were elevated at the midline and flap survival was measured 7 d after surgery. Pathologic review of the skin flap specimen was performed in a subset of animals. In the second experiment, for evaluation of the role of NO, an NO synthase inhibitor N-nitro-L-arginine methyl ester hydrochloride (L-NAME) was administered with and without the effective dose of metformin. In the next experiment, subtherapeutic dose of NO precursor, L-Arginine, was administered with and without subeffective dose of metformin. RESULTS:Metformin pretreatment at doses of 200 and 300 mg/kg significantly increased skin flap survival rate. However, administration of L-NAME abolished the protective effects of metformin. On the other hand, subtherapeutic dose of L-arginine augmented the effects of low-dose metformin and significantly increased skin flap survival. Skin flaps from those rats that received 300 mg/kg metformin pretreatment and those treated with subtherapeutic doses of L-arginine and metformin showed increased vasodilation compared with control group. CONCLUSIONS:Metformin pretreatment can improve skin flap survival through an NO dependent pathway.
Authors: Ronen Schuster; Or Bar-Nathan; Alon Tiosano; Eli C Lewis; Eldad Silberstein Journal: Adv Wound Care (New Rochelle) Date: 2019-07-02 Impact factor: 4.730