Abstract

The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

Highlights

  • The liver is a target organ that is damaged during the pathogenesis of septic shock

  • Effect of exogenous normal lymph (ENL) on hepatic histomorphology in LPS rats The clear architecture of hepatic lobules, with their regular arrayed hepatic cords, as well as the uniformsized hepatic cells with round nuclei and clear karyolemmas were observed in the control group (Figure 1A)

  • We found that administration of ENL could significantly reduce LPS-induced increases in AST and ALT levels in plasma and attenuate the degree of hepatic tissue damage

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Summary

Introduction

The liver is a target organ that is damaged during the pathogenesis of septic shock. The spread of endotoxins usually begins from this organ, which contributes to the development of multiple-organ dysfunction syndrome; liver protection is significant in endotoxemia treatment [1,2,3]. Numerous studies have been conducted on liver injury after serious infection or sepsis [4,5], but no effective treatment for liver injury induced by septic shock has been reported. Previous studies have found that normal lymph has beneficial therapeutic effects on microcirculatory disturbances in rats with hemorrhagic shock; its effect is significantly better than that by the same amount of normal saline and of albumin [6]. Exogenous normal lymph (ENL) from healthy dogs has an alleviating effect on microcirculation disturbances and abnormal hemorheological properties in rats with disseminated intravascular coagulation induced by Dextran 500 [7]. ENL could alleviate acute lung injury and acute kidney injury in rats with endotoxic shock induced by lipopolysaccharides (LPS) [8,9]. The present study evaluated the effect of ENL on LPS-induced liver injury and its underlying mechanisms

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