PMO-127 Biological effects of oral nanoporous carbon in bile duct ligated rats

Abstract

and bacterial challenge at baseline, and following 2 h stimulation with lipopolysaccharide (LPS) and ammonia. Pro-and anti-inflammatory cytokines were determined by CBA. Results Baseline neutrophil TLR9 expression was significantly higher in patients with HE (ALF: Grade 3/4 vs controls: p<0.02, vs grade 0e2: p<0.03) (Cirrhotics: Grade 3/4 vs controls: p<0.03, vs grade 0e2: p<0.05). Moreover their baseline TLR9 expression was associated with severity of HE and higher IL6 and IL8 levels. CD16 expression was downregulated by a median of 45% (range 25%e 85%) in ALF patients with grade 3/4 HE compared to controls and in cirrhotics by a median of 88% (range 5%e90%) (Grade 3/4 vs controls: p<0.05). Baseline CD11b expression did not differ between controls and patients. Exposure to LPS and ammonia upregulated TLR9 and CD11b and downregulated CD16. Conclusion Neutrophil TLR9 expression in patients with ALF and cirrhosis serves as a useful biomarker that differentiates those who develop high grade HE from those who do not. High baseline TLR9 expression and low CD16 expression promote a pro-inflammatory cytokine milieu that may help to explain the propensity to develop infection and why inflammation hastens the development of HE. TLR9 antagonists may be of therapeutic value in restoring neutrophil activity.

Targeting the gut-liver axis in liver disease

“…Proof-of-concept studies administering Yaq-001 to bile duct ligated rats, confirmed its impact on the removal of these molecules and results in pleiotropic beneficial effects, characterised by a reduction in the severity of endotoxaemia, liver injury, markers of systemic and hepatic inflammation, portal hypertension, renal dysfunction and severity of hepatic encephalopathy. 109 It is important to note that this effect is not associated with any antibacterial properties in vitro, but changes in the microbiome of the bile duct ligated rats was observed when administered in vivo. 110 Although the significance of these changes is not clear, the data indicated that alterations to the microenvironment, induced by Yaq-001, change the gut microbial flora.…”

“…It is regulated as a device in Europe and its oral administration could reduce the trans-intestinal migration of bacterial endotoxins produced by organisms resident in the gut. 109 In vitro studies have shown that Yaq-001 preferentially removes hydrophobic substances and those with molecular weights up to approximately 70kDa. Therefore, Yaq-001 can adsorb gut-derived toxins such as ammonia, asymmetric dimethylarginine, acetaldehyde, hydrophobic BA, cytokines such as TNF alpha and interleukin-6, as well as bacteria derived products like LPS and exotoxins (Fig.…”

The gut–liver axis in sepsis: interaction mechanisms and therapeutic potential

“…Indeed, cation-exchange resin targeting hyperkalemia and hyperphosphatemia has shown efficacy [ 160 ]. Nonabsorbable nanopore carbon reduced portal vein pressure and liver biochemical markers in rats that underwent bile duct ligation, resulting in decreased endotoxin-induced KC stimulation [ 161 , 162 ]. Therefore, by targeting the gut–liver axis, adsorbent materials is a possible treatment strategy for sepsis.…”