Fatih Bal1, Seldag Bekpinar1, Yesim Unlucerci1, Zeynep Kusku-Kiraz1, Semen Önder2, Mujdat Uysal1, Figen Gurdol3. 1. Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Capa, Istanbul 34093, Turkey. 2. Istanbul University, Istanbul Faculty of Medicine, Department of Pathology, Capa, Istanbul 34093, Turkey. 3. Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Capa, Istanbul 34093, Turkey. Electronic address: figur@istanbul.edu.tr.
Abstract
AIMS: We aimed to investigate the pharmacological efficiency of metformin on asymmetric dimethylarginine (ADMA) metabolism in inflammation caused by the lipopolysaccharide (LPS)/D-galactosamine (D-GalN) treatment. METHODS: Adult Sprague-Dawley rats were injected LPS/D-GalN intraperitoneally. One half of the animals was injected metformin (250 mg kg(-1) body mass for one week) prior to LPS/D-GalN treatment. Six hours after the LPS/D-GalN injection, livers were removed, and used for the measurements of dimethylarginine dimethylaminohydrolase (DDAH) and myeloperoxidase (MPO) activities, glutathione (GSH), ADMA and arginine levels. Liver tissues were examined histopathologically. The Kruskal-Wallis (posthoc Mann-Whitney U) test was used for the statistics. LPS/D-GalN injections caused liver injury as evidenced by the activities of aminotransferases and arginase. GSH level and DDAH activity were decreased in the liver. Metformin pretreatment alleviated the activity of serum enzymes, and attenuated histopathological lesions caused by LPS/D-GalN injections. LPS/D-GalN-induced inflammation, as confirmed by the increased MPO activity, created an asymmetrical distribution of arginine and ADMA between the tissue and plasma. Metformin decreased tissue ADMA level while it restored the DDAH activity and GSH. CONCLUSION: Our findings showed that metformin administration for one week has a potency to protect liver through regulating ADMA metabolism in LPS/D-GalN-induced injury.
AIMS: We aimed to investigate the pharmacological efficiency of metformin on asymmetric dimethylarginine (ADMA) metabolism in inflammation caused by the lipopolysaccharide (LPS)/D-galactosamine (D-GalN) treatment. METHODS: Adult Sprague-Dawley rats were injected LPS/D-GalN intraperitoneally. One half of the animals was injected metformin (250 mg kg(-1) body mass for one week) prior to LPS/D-GalN treatment. Six hours after the LPS/D-GalN injection, livers were removed, and used for the measurements of dimethylarginine dimethylaminohydrolase (DDAH) and myeloperoxidase (MPO) activities, glutathione (GSH), ADMA and arginine levels. Liver tissues were examined histopathologically. The Kruskal-Wallis (posthoc Mann-Whitney U) test was used for the statistics. LPS/D-GalN injections caused liver injury as evidenced by the activities of aminotransferases and arginase. GSH level and DDAH activity were decreased in the liver. Metformin pretreatment alleviated the activity of serum enzymes, and attenuated histopathological lesions caused by LPS/D-GalN injections. LPS/D-GalN-induced inflammation, as confirmed by the increased MPO activity, created an asymmetrical distribution of arginine and ADMA between the tissue and plasma. Metformin decreased tissue ADMA level while it restored the DDAH activity and GSH. CONCLUSION: Our findings showed that metformin administration for one week has a potency to protect liver through regulating ADMA metabolism in LPS/D-GalN-induced injury.
Authors: Daniel M Rotroff; Noffisat O Oki; Xiaomin Liang; Sook Wah Yee; Sophie L Stocker; Daniel G Corum; Michele Meisner; Oliver Fiehn; Alison A Motsinger-Reif; Kathleen M Giacomini; Rima Kaddurah-Daouk Journal: Front Pharmacol Date: 2016-06-14 Impact factor: 5.810