Thymoquinone modulates nitric oxide production and improves organ dysfunction of sepsis

Aims: The present investigation was designed to evaluate the effect of thymoquinone in a septic animal model and to explore the role of nitric oxide (NO) in the process. Main methods: To achieve this, mice (n = 12 per group) were treated in parallel with thymoquinone (0.75 mg/kg/day) and/or NG-nitro-L-arginine methyl ester (L-NAME; 400 mu g/g/day) prior to sepsis induction with live Escherichia coli. Key findings: Thymoquinone significantly improved renal and hepatic functions alone and in combination with L-NAME. This was associated with less NO production and lower oxidative stress in treated animals. Tumor necrosis factor-a concentration with thymoquinone and L-NAME were 3627 +/- 3.41 pg/ml and 56.55 +/- 5.85 pg/ml, respectively, as opposed to 141.11 6.46 pg/ml in septic controls. Similarly, Interleukin-la, 2,6 and 10 levels decreased significantly upon treatment with thymoquinone and L-NAME as compared with untreated septic animals. NF-kappa B and NF-kappa B-DNA binding activity in nuclear proteins were also significantly down-regulated. Vascular responsiveness studies in isolated mouse aortae demonstrated a reduced relaxation to acetylcholine exposure in septic mice treated with thymoquinone. Significance: These findings suggest that thymoquinone prevents sequels of the multiple organ failure syndrome of sepsis by modulating the production of NO and its inflammatory sequela, and adjusting vascular responsiveness. (C) 2015 Elsevier Inc. All rights reserved.