ABSTRACT
The present study was aimed to investigate the role and mechanisms of kallistatin in protection against oxidative stress-induced hepatic stellate cell damage. The effects of kallistatin on the viability, the intracellular superoxide level and Akt, eNOS molecules were investigated in human hepatic stellate cell line LX-2 and the incompletely activated primary rat hepatic stellate cells. Two different oxidative-stress related models, the hydrogen peroxide model and the iron-overload model were used in the experiments. The results show that kallistatin protected the hepatic stellate cells from oxidative damage and repaired the cell damage by oxidative stress. The main mechanism is antioxidant activity of kallistatin, which can remove the oxidized substances inside the cells. On the other way, kallistatin activates Akt and eNOS molecules to generate the antioxidant effect. Our results help to explore new anti-fibrotic targets.
ABSTRACT
This study was designed to evaluate the anti-inflammatory effect of recombinant human kallistatin (Kal) on ulcerative colitis (UC) in the mouse model. Acute colitis was induced by administration of 4% dextran sodium suffate (DSS) to KM mice for 7 days. The mice were then randomized into 5 groups:model control, Kal 0.2 mg·kg-1·d-1, 1.0 mg·kg-1·d-1 and 2.0 mg·kg-1·d-1 group, salazosulfapyridine (SASP) group. Ten age-matched normal KM mouse were administered with saline in the normal control. The weight, colon length, inflammation factor (MPO/SOD/MDA) and TNF-α/IL-10 levels among the five groups of mice were determined. The results showed that histological index score and MPO/MDA/TNF-α levels of high-dose Kal treatment group and SASP group were significantly lower compared with the model group (PPα/IL-10 levels and has some antioxidant activity.