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Abstract Title:

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

Abstract Source:

Life Sci. 2015 Aug 15. Epub 2015 Aug 15. PMID: 26285172

Abstract Author(s):

Khalid M Alkharfy, Ajaz Ahmad, Mohammad Raish, Paul M Vanhoutte

Article Affiliation:

Khalid M Alkharfy

Abstract:

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 (0.75mg/kg/day) and/or NG-nitro-l-arginine methyl ester (L-NAME; 400μg/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-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.

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.

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Sayer Ji
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