Antidiabetic drug metformin is effective on the metabolism of asymmetric dimethylarginine in experimental liver injury

• Published in: Diabetes research and clinical practice 2014-11, Vol.106 (2), p.295-302
• Main Authors: Bal, Fatih, Bekpinar, Seldag, Unlucerci, Yesim, Kusku-Kiraz, Zeynep, Önder, Semen, Uysal, Mujdat, Gurdol, Figen
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - metabolism; Amidohydrolases - metabolism; Animals; Arginine; Arginine - analogs & derivatives; Arginine - metabolism; Aspartate Aminotransferases - metabolism; Asymmetric dimethylarginine; Chemical and Drug Induced Liver Injury - drug therapy; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Dimethylarginine dimethylaminohydrolase; Endocrinology & Metabolism; Galactosamine; Glutathione - metabolism; Hypoglycemic Agents - administration & dosage; Inflammation; Lipopolysaccharides; Liver injury; Male; Metformin; Metformin - administration & dosage; Peroxidase - metabolism; Protective Agents - administration & dosage; Rats; Rats, Sprague-Dawley
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/j.diabres.2014.08.028

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.