Pro-Resolving Lipid Mediator Resolvin E1 Mitigates the Progress of Diethylnitrosamine-Induced Liver Fibrosis in Sprague-Dawley Rats by Attenuating Fibrogenesis and Restricting Proliferation

Autor: Jessica Zúñiga-Hernández, Wendy Donoso, Daniel R. Gonzalez, María José Rodríguez, Iván Castillo, Francisca Herrera, Roxana Orrego
Rok vydání: 2020
Předmět:
Liver Cirrhosis
Male
0301 basic medicine
Antioxidant
medicine.medical_treatment
Chronic liver disease
Rats
Sprague-Dawley
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
omega-3 derivatives
Fibrosis
Diethylnitrosamine
lcsh:QH301-705.5
Spectroscopy
liver fibrosis
NF-kappa B
apoptosis
Alanine Transaminase
General Medicine
Computer Science Applications
Eicosapentaenoic Acid
Liver
030220 oncology & carcinogenesis
medicine.medical_specialty
NF-E2-Related Factor 2
Protective Agents
Article
eicosanoids
Catalysis
Inorganic Chemistry
03 medical and health sciences
Internal medicine
Lactate dehydrogenase
medicine
Animals
Physical and Theoretical Chemistry
Molecular Biology
Cell Proliferation
L-Lactate Dehydrogenase
Organic Chemistry
Glutathione
medicine.disease
Rats
030104 developmental biology
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
microsteatosis
chemistry
Apoptosis
Glutathione disulfide
Steatosis
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 22
International Journal of Molecular Sciences, Vol 21, Iss 8827, p 8827 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21228827
Popis: Liver fibrosis is a complex process associated to most types of chronic liver disease, which is characterized by a disturbance of hepatic tissue architecture and the excessive accumulation of extracellular matrix. Resolvin E1 (RvE1) is a representative member of the eicosapentaenoic omega-3 lipid derivatives, and is a drug candidate of the growing family of endogenous resolvins. Considering the aforementioned, the main objective of this study was to analyze the hepatoprotective effect of RvE1 in a rat model of liver fibrosis. Male Sprague-Dawley rats received diethylnitrosamine (DEN, 70 mg/mg body weight intraperitoneally (i.p)) as an inductor of liver fibrosis once weekly and RvE1(100 ng/body weight i.p) twice weekly for four weeks. RvE1 suppressed the alterations induced by DEN, normalizing the levels of alanine aminotransferase (ALT), albumin, and lactate dehydrogenase (LDH), and ameliorated DEN injury by decreasing the architecture distortion, inflammatory infiltration, necrotic areas, and microsteatosis. RvE1 also limited DEN-induced proliferation through a decrease in Ki67-positive cells and cyclin D1 protein expression, which is related to an increase of the levels of cleaved caspase-3. Interestingly, we found that RvE1 promotes higher nuclear translocation of nuclear factor &kappa
B (NF-&kappa
B)p65 than DEN. RvE1 also increased the levels of nuclear the nuclear factor erythroid 2&ndash
related factor 2 (Nrf2), but with no antioxidant effect, measured as an increase in glutathione disulfide (GSSG) and a decrease in the ratio of glutathione (GSH)/GSSG. Taken together, these results suggest that RvE1 modulates the fibrogenesis, steatosis, and cell proliferation in a model of DEN induced fibrosis.
Databáze: OpenAIRE
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