Blood Levels of Glutamine and Nitrotyrosine in Patients with Chronic Viral Hepatitis

Abstract

Hussam Murad,1,2 Haythum Tayeb,3 Mahmoud Mosli,4 Misbahuddin Rafeeq,1 Mohammed Basheikh5 1Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 3Department of Medicine, Division of Neurology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Medicine, Division of Gastroenterology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 5Department of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Hussam Murad Tel + 966541541341Fax + 966024223031Email [email protected]; [email protected]: Oxidative stress is involved in pathogenesis of chronic viral hepatitis. Glutamine is an antioxidant, but there is a controversy about its risk-benefits. Nitrotyrosine is an oxidative stress marker. This observational cross-sectional study was designed to compare blood levels of glutamine and nitrotyrosine in treated versus untreated chronic viral hepatitis patients.Patients and Methods: Five groups (n = 250) were included: hepatitis B untreated (HBV), hepatitis C untreated (HCV), HBV treated (HBVT), and HCV treated (HCVT) groups plus a normal control group. Liver function tests and blood levels of glutamine, nitrotyrosine, viral loads, and HBsAg were measured.Results: Blood levels of glutamine and nitrotyrosine in all patient groups significantly increased compared with normal controls with non-significant differences in-between. Both tests showed significant large correlations with HBV-DNA or HCV-RNA test positivity, high accuracies, and cutoff scores with high sensitivities and specificities. The viral loads and HBsAg levels were significantly lower in treated versus untreated groups. However, they poorly correlated with levels of glutamine and nitrotyrosine in all patient groups.Conclusion: Blood levels of glutamine and nitrotyrosine significantly increased in treated and untreated chronic viral hepatitis B and C patients compared with normal controls. Both tests showed high accuracies and cutoff scores with high sensitivities and specificities. However, they did not differ significantly in treated versus untreated patients. To our knowledge, this is the first data showing elevation of glutamine and nitrotyrosine in treated and untreated chronic viral hepatitis. A prospective longitudinal study with repeated measurements of glutamine and nitrotyrosine is recommended to verify if they can predict response to treatment. Study of other oxidative stress markers is also advised to clarify if the elevated nitrotyrosine could be an oxidative stress marker in these patients, and whether the increased glutamine could act as an antioxidant or as a predictive agent for deleterious consequences.Keywords: glutaminolysis, nitrotyrosination, oxidant stress

Keywords

• glutaminolysis
• nitrotyrosination
• oxidant stress