Abstract
Under septic conditions, Kupffer cells produce pro-inflammatory mediators which contribute to hepatic dysfunction, and whose levels can be modulated by endogenous factors including neurotransmitters such as norepinephrine (NE). We investigated the ability of NE to suppress Kupffer cell activation, in particular its effects on induction and activity of the inducible form of nitric oxide synthase (NOSII), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α). In the present study used twenty one male NMRI mice (25 ± 5 g) that they divided into tree groups (n = 7). Negative control (normal saline), positive control (LPS), NE (∼100 nM) is injected through the mouse tail vein 30 minutes before inducts inflammation by LPS (5 mg/kg for intraperitoneal). Changes in the levels of expression of TNF-α, IL-6 and iNOS genes in the liver induced by LPS injection for two hours studied by a semi quantitative RT-PCR method. The results showed that administration of LPS increased hepatic TNF-α, IL-6 and iNOS mRNAs. NE (∼100 nM) reduces TNF-α, IL-6 and iNOS mRNA levels two hours after the injection. The most important have remarked effect norepinephrine in reducing iNOS; on the other hand, NE has a better influence on iNOS in liver tissue. These results indicate that high concentration of NE effectively suppress LPS-induced TNF-α, IL-6 and iNOS expression from liver tissue, suggesting that the down regulatory effect of NE on pro-inflammatory cytokine may represent a mechanism responsible for their beneficial effects in preventing inflammatory responses and tissue damage in sepsis.
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Abrehdari, Z., Pirestani, M., Allahdini, P. et al. Characterization of anti-inflammatory responses of norepinephrine in hepatitis induced by LPS: Effects on expression of IL-6, TNF-α and iNOS in liver of mice. Neurochem. J. 8, 193–198 (2014). https://doi.org/10.1134/S1819712414030027
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DOI: https://doi.org/10.1134/S1819712414030027