Thymoquinone modulates nitric oxide production and improves organ dysfunction of sepsis.
OBJECTIVE
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.


METHODS
To achieve this, mice (n=12 per group) were treated in parallel with thymoquinone (0.75mg/kg/day) and/or NG-nitro-l-arginine methyl ester (L-NAME; 400μg/g/day) prior to sepsis induction with live Escherichia coli.


RESULTS
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-α concentration with thymoquinone and L-NAME were 36.27±3.41pg/ml and 56.55±5.85pg/ml, respectively, as opposed to 141.11±6.46pg/ml in septic controls. Similarly, Interleukin-1α, 2, 6 and 10 levels decreased significantly upon treatment with thymoquinone and L-NAME as compared with untreated septic animals. NF-κB and NF-κB-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.


CONCLUSIONS
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.
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Biomarkers Research Program, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: alkharfy@ksu.edu.sa.
Khalid M
KM
Alkharfy
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Ajaz
A
Ahmad
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Mohammad
M
Raish
State Key Laboratory for Pharmaceutical Biotechnologies, Faculty of Medicine, the University of Hong Kong, Hong Kong, China; Department of Pharmacology and Pharmacy, Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
Paul M
PM
Vanhoutte
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009924:Organ Culture Techniques; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism
D016227:Benzoquinones; D018836:Inflammation Mediators; D009569:Nitric Oxide; C003466:thymoquinone
Cytokines; E. coli; L-NAME; Nitric oxide; Sepsis; Thymoquinone