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Ulinastatin attenuates liver injury and inflammation in a cecal ligation and puncture induced sepsis mouse model
Author(s) -
Song Yukang,
Miao Shixing,
Li Yexuzi,
Fu Hui
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27396
Subject(s) - ulinastatin , sepsis , medicine , lipopolysaccharide , inflammation , nitrotyrosine , pharmacology , liver injury , cytokine , immunology , gastroenterology , nitric oxide synthase , nitric oxide
Sepsis is a syndrome of life‐threatening multiorgan dysfunction caused by host response dysregulation to infection. Ulinastatin (UTI), a serine protease inhibitor, possesses anti‐inflammatory properties and has been suggested to modulate lipopolysaccharide‐induced sepsis. However, little is known about the mechanism underlying its effects on sepsis. In the current study, we investigated the protective effect of UTI on liver injury in a cecal ligation and puncture (CLP)‐induced sepsis of C57BL/6 mouse model and explored the possible mechanisms. Mice underwent CLP as sepsis models and were randomized into five groups including the sham group, UTI group, CLP group, UTI‐L group, and UTI‐H group. UTI was intraperitoneally administered at doses of UTI 1500 U/100 g (UTI‐L group) or 3000 U/100 g (UTI‐H group), before CLP. The mice were killed, and immunohistochemical changes, cytokine levels, and antioxidant enzyme activities were detected. Our results showed that UTI ameliorated CLP‐mediated increases in serum aspartate aminotransferase and alanine aminotransferase activities, histological activity index, degenerative region ratio, and infiltrated inflammatory cell numbers. Moreover, UTI also decreased nitrotyrosine and 4‐hydroxynonenal, activated caspase‐3, and activated poly (ADP‐ribose) polymerase (PARP) levels and inhibited the mitogen‐activated protein kinase pathway activation in liver tissues. Our results indicated that UTI could inhibit CLP‐induced liver injury by suppressing inflammation and oxidation. Our results indicated that UTI may serve as a potential therapeutic agent for sepsis.