Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock: Downstream Regulation of COX-2, IL-1𝜷, TNF-𝜶, IL-6, and HMGB1 Expression

Table 4

Effects of HOCbl on pro-inflammatory cytokine gene expression, at 24 h following LPS-induced endotoxaemia.

Gene	Organ	LPS	LPS + HOCbl	𝑃 value (versus LPS)
IL-1𝛽	Liver	−8.30±0.30	−10.6 ± 0.3*	0.0056
	Lung	2.70±0.50	2.1 ± 0.1	0.3046
TNF-𝛼	Liver	−86.90±0.10	−68.6 ± 0.2*	<0.0001
	Lung	−2.10±0.20	−11.4 ± 0.1*	<0.0001

Mice were treated with HOCbl at the low dose protocol (0.2 mg/kg i.p. at −1 h, +1 h, +2 h, +6 h, and +22 h) and compared to LPS only (0.1 mg/kg i.p. at time 0 h). Twenty-four hours after LPS stimulation, organs (liver and lung) were harvested and processed for assessment of IL-1𝛽, TNF-𝛼, gene expression by real-time PCR, using GAPDH and RPL32 as internal standards. Values are a mean ± SEM of triplicate observations. *denotes statistical significance for 𝑃<0.05.