Pretreatment with Zinc protects Kupffer cells following administration of microbial products

Background:

Serum zinc level has been suggested as independent predictor of hepatic decompensation and supplementation of Zinc protects against alcohol induced liver injury and bacterial infections in both clinical and animal experiments.

Objectives:

We aimed at investigating the relation between Zinc and liver function and the involved mechanisms of Zinc to protect non-parenchymal cells following microbial infections.

Methods:

190 patients with different chronic liver disease were divided into 3 groups according to their serum Zinc levels: low group ≤59; middle group 60 – 74 and normal group ≥75 (µg/dl; n = 64, 49 and 77). Meld score and other markers were compared in these three groups. For in vitro experiments, THP-1 macrophages and human primary nonparenchymal liver cells [Kupffer cells (KCs), sinusoidal endothelial cells (SECs), and hepatic stellate cells (HSCs)] were investigated. These cells were stimulated by microbial isolates derived from patients with SBP with or without Zinc sulfate pretreatment. LDH and inflammatory cytokines in supernatants were determined; qPCR and Western blot were investigated for relevant pathways.

Result:

Low Zinc group had much higher Meld than middle and normal Zinc groups, while no significant difference was found between middle and normal Zinc groups. Bacterial isolates significantly increased LDH levels in KCs and HSCs but had no effects in SECs. 24 hours pretreatment with 20µM Zinc sulfate solution protected KCs but failed to decrease LDH levels in HSCs after microbial stimulation. Zn pretreatment also inhibited the release of inflammatory cytokines and activation of Myd88 related pathway in KCs following bacterial stimulation.

Conclusion:

Low Zinc level is related to higher Meld with a low boundary of and 60 µg/dl. A safe and easy supplementation might be useful as effective pretreatment for patients with liver diseases especially to attenuate the course of bacterial infections in liver cirrhosis. Both KCs and HSCs responded to bacterial isolates while Zinc pretreatment only had protective effects in KCs. Zinc pretreatment inhibited the expression of Myd88, MAPK and NF-kB following bacterial infections.