Crocetin protects against fulminant hepatic failure induced by lipopolysaccharide/D‑galactosamine by decreasing apoptosis, inflammation and oxidative stress in a rat model

Gao,Ke; Liu,Faquan; Chen,Xi; Chen,Mengxue; Deng,Qingwen; Zou,Xingjian; Guo,Hongxing

doi:10.3892/etm.2019.8030

Crocetin protects against fulminant hepatic failure induced by lipopolysaccharide/D‑galactosamine by decreasing apoptosis, inflammation and oxidative stress in a rat model

Authors:
- Ke Gao
- Faquan Liu
- Xi Chen
- Mengxue Chen
- Qingwen Deng
- Xingjian Zou
- Hongxing Guo
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Affiliations: Department of Pathology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510900, P.R. China, Department of Gastroenterology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510900, P.R. China, Department of Ears, Nose and Throat, The Third People's Hospital of Shenzhen, Shenzhen, Guangdong 518115, P.R. China
Published online on: September 19, 2019 https://doi.org/10.3892/etm.2019.8030
Pages: 3775-3782
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fulminant hepatic failure (FHF) is a clinical syndrome characterized by sudden and severe liver dysfunction. Apoptosis and inflammation are essential for the pathogenesis of FHF. Crocetin, the major component present in saffron, has been reported to possess anti‑inflammatory and antioxidant functions; however, its role in FHF is poorly understood. The aim of this study was to explore the protective effects of crocetin against lipopolysac§§charide (LPS)/D‑galactosamine (D‑GalN)‑induced FHF and the underlying mechanisms in a rat model. For the in vivo study, rats were assigned to the LPS/D‑GalN group or to the crocetin pre‑treatment+LPS/D‑GalN group. Each group was then further divided according to the different LPS/D‑GalN treatment times of 0, 6, 12 or 48 h. The results demonstrated that crocetin pre‑treatment efficiently protected against LPS/D‑GalN‑induced FHF by improving liver tissue morphology, reducing total bilirubin generation and decreasing the activities of alanine transaminase and aspartate aminotransferase. Moreover, crocetin pre‑treatment significantly decreased hepatocyte apoptosis, p53 mRNA expression and the expression of proteins in the caspase family and the Bcl‑2 pro‑apoptotic family following LPS/D‑GalN treatment. Furthermore, crocetin also decreased the secretion of pro‑inflammatory cytokines in the serum and in the liver via suppression of NF‑κB activation, and also suppressed hepatic oxidative stress. In conclusion, crocetin protected against LPS/D‑GalN‑induced FHF and inhibited apoptosis, inflammation and oxidative stress. The underlying mechanisms may be related to the regulation of apoptotic proteins in the caspase family and the Bcl‑2 family, as well as the modulation of NF‑κB expression. Therefore, crocetin may be used as a novel therapy for preventing FHF.

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