Increased circulating peroxiredoxin-4 in sepsis model rats involves secretion from hepatocytes and is mitigated by GYY4137.

Increased circulating peroxiredoxin-4 in sepsis model rats involves secretion from hepatocytes and is mitigated by GYY4137. J Toxicol Pathol. 2019 Oct;32(4):305-310 Authors: Unuma K, Yoshikawa A, Aki T, Uemura K Abstract Circulating peroxiredoxin-4 (Prx4) is suggested as a prognosis marker as well as a regulator of many diseases. We aimed to examine 1) whether Prx4 is secreted from the liver in an animal model of sepsis and 2) effects of GYY4137, a hydrogen sulfide donor molecule, on septic liver injury as well as the hepatic secretion of Prx4. Rats (Wistar, male, 6 weeks old) were administered lipopolysaccharide (LPS, 15 mg/kg body weight, i.p.) with or without pre-administration of GYY4137 (50 mg/kg body weight, i.p.) and sacrificed 24 h after LPS administration. Hematoxylin-eosin and Elastica Masson-Goldner stains were used to evaluate hepatic injuries. Cytokine expression levels were determined by qPCR, and the levels of Prx4 in the serum and liver were determined by immunoblotting. Hepatocytes were isolated from rat liver, and the levels of Prx4 in the medium as well as the cells were determined 24 h after the administrations of LPS (1 µg/ml), tumor necrosis factor-α (TNFα, 50 ng/ml), or interleukin-1β (IL-1β, 10 ng/ml), with or without GYY4137 (300 µM). Hepatic inflammation and damage in LPS-administered rats were suppressed by GYY4137. An increase in plasma Prx4 level caused by LPS was observed, but the increase was atte...
Source: Journal of Toxicologic Pathology - Category: Toxicology Tags: J Toxicol Pathol Source Type: research