Dataset Information

Astaxanthin alleviated ethanol-induced liver injury by inhibition of oxidative stress and inflammatory responses via blocking of STAT3 activity.

ABSTRACT: Astaxanthin (AXT) is classified as a xanthophyll carotenoid compound which have broader functions including potent antioxidant, anti-inflammatory and neuroprotective properties. Considerable researches have demonstrated that AXT shows preventive and therapeutic properties against for Diabetes, Osteoarthritis and Rheumatoid Arthritis. However, the protective effect of AXT on liver disease has not yet been reported. In this study, we investigated effects of AXT on ethanol-induced liver injury in chronic plus binge alcohol feeding model. The hepatic steatosis and inflammation induced by ethanol administration were alleviated by AXT. Serum levels of aspartate transaminase and alanine transaminase were decreased in the livers of AXT administrated group. The ethanol-induced expression of cytochrome P450 2E1 (CYP2E1), pro-inflammatory proteins, cytokines, chemokines and reactive oxygen species (ROS) levels were also reduced in the livers of AXT administrated group. Moreover, ethanol-induced infiltration of neutrophils was decreased in the livers of AXT administrated group. Docking model and pull-down assay showed that AXT directly binds to the DNA binding site of STAT3. Moreover, AXT decreased STAT3 phosphorylation in the liver of AXT administration group. Therefore, these results suggest that AXT could prevent ethanol-induced hepatic injury via inhibition of oxidant and inflammatory responses via blocking of STAT3 activity.

SUBMITTER: Han JH

PROVIDER: S-EPMC6148091 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Astaxanthin alleviated ethanol-induced liver injury by inhibition of oxidative stress and inflammatory responses via blocking of STAT3 activity.

Han Ji Hye JH Ju Jung Heun JH Lee Yong Sun YS Park Ju Ho JH Yeo In Jun IJ Park Mi Hee MH Roh Yoon Seok YS Han Sang Bae SB Hong Jin Tae JT

Scientific reports 20180920 1

Astaxanthin (AXT) is classified as a xanthophyll carotenoid compound which have broader functions including potent antioxidant, anti-inflammatory and neuroprotective properties. Considerable researches have demonstrated that AXT shows preventive and therapeutic properties against for Diabetes, Osteoarthritis and Rheumatoid Arthritis. However, the protective effect of AXT on liver disease has not yet been reported. In this study, we investigated effects of AXT on ethanol-induced liver injury in c ...[more]

PMID: 30237578

Similar Datasets

Project description:Introduction: Chronic stress has been shown to cause liver damage in addition to psychological depression. Besides, drug-induced liver injury is frequently caused by antidepressants. Shuxie-1 decoction (SX-1) is a formula of traditional Chinese medicine commonly used in nourishing liver blood, and relieving depression. However, the underlying molecular mechanism remains unclear. Therefore, this study was designed to explore the effects and mechanisms of SX-1 in treating chronic stress-induced depression as well as liver injury. Methods: Chronic unpredictable mild stress (CUMS) was applied to male Wistar rats for 4 weeks, with or without administration of SX-1 at low-dose and high-dose for 6 weeks, using Fluoxetine (Flu) as a positive control. Body weight was monitored once every 2 weeks. In the sixth week, the sugar preference test and open field test were carried out to evaluate the depression status. After that, the serum and liver tissues were collected. The quality control of SX-1 decoctions and drug-containing serum was controlled by UHPLC-QE-MS. The cell viability was measured by Cell Counting Kit-8 (CCK8). Enzyme-linked immunosorbent assay (Elisa), Western Blot and immunohistochemistrical staining was obtained to detect the protein levels in the plasma and the hepatic tissues, respectively. Results: CUMS led to decreased 1) body weight, 2) the preference for sugar water, 3) the desire to explore in open field, and increased serum levels of corticosterone. All these factors were completely reversed by SX-1 treatment. Hematoxylin-eosin staining (HE) showed that SX-1 improved the hepatocyte vacuolization in CUMS treated rats, decreased the serum levels of alanine aminotransferase (ALT) and the deposition of type I collagen (Col I) in hepatocytes as well. CUMS increased the levels of hepatic Interleukin-6 (IL-6), and provoked the activation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), which was abrogated by SX-1 treatment. Cobalt chloride (CoCl2) increased the protein expression of IL-6 and p-STAT3 in AML12 cells. Besides, nuclear pyknosis was observed under electron microscope, which were recovered after rat SX serum. Conclusion: SX-1 effectively ameliorated CUMS-induced depression-like behaviors as well as hepatic injuries, probably by the blockade of hepatic IL-6/JAK2/STAT3 signaling.

Project description:The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression, and participates in cytokine secretion in many diseases. However, the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid hemorrhage remain to be studied. A subarachnoid hemorrhage model was established in rats by infusing autologous blood into the optic chiasm pool. Some rats were first treated with JAK2/STAT3 small interfering RNA (Si-JAK2/Si-STAT3) or overexpression plasmids of JAK2/STAT3. In the brains of subarachnoid hemorrhage model rats, the expression levels of both JAK2 and STAT3 were upregulated and the expression of SOCS1 was downregulated, reaching a peak at 48 hours after injury. Simultaneously, the interactions between JAK2 and SOCS1 were reduced. In contrast, the interactions between JAK2 and STAT3 were markedly enhanced. Si-JAK2 and Si-STAT3 treatment alleviated cortical neuronal cell apoptosis and necrosis, destruction of the blood-brain barrier, brain edema, and cognitive functional impairment after subarachnoid hemorrhage. This was accompanied by decreased phosphorylation of JAK2 and STAT3 protein, decreased total levels of JAK2 and STAT3 protein, and increased SOCS1 protein expression. However, overexpression of JAK2 and STAT3 exerted opposite effects, aggravating subarachnoid hemorrhage-induced early brain injury. Si-JAK2 and Si-STAT3 inhibited M1-type microglial conversion and the release of pro-inflammatory factors (inducible nitric oxide synthase, interleukin-1β, and tumor necrosis factor-α) and increased the release of anti-inflammatory factors (arginase-1, interleukin-10, and interleukin-4). Furthermore, primary neurons stimulated with oxyhemoglobin were used to simulate subarachnoid hemorrhage in vitro, and the JAK2 inhibitor AG490 was used as an intervention. The in vitro results also suggested that neuronal protection is mediated by the inhibition of JAK2 and STAT3 expression. Together, our findings indicate that the SOCS1/JAK2/STAT3 axis contributes to early brain injury after subarachnoid hemorrhage both in vitro and in vivo by inducing inflammatory responses. This study was approved by the Animal Ethics Committee of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China (approval No. LLSC-20180202) on March 1, 2018.

Project description:Silybin (Si) is the main element of silymarin isolated from the seeds of Silybum marianum L. Gaernt., which has superior antioxidant properties. However, the protective role of Si in maintaining liver health under oxidative stress remains ambiguous. This study aimed to investigate the underlying mechanism of the beneficial effect of dietary Si against hepatic oxidative injury induced by paraquat (PQ) in weaned piglets. A total of 24 piglets were randomly allocated to four treatments with six replicates per treatment and 1 piglet per replicate: the control group; Si group; PQ group; and Si + PQ group. Piglets in the control group and PQ group were given a basal diet, while piglets in the Si and Si + PQ groups were given a Si-supplemented diet. On the 18th day, the pigs in the PQ treatment group received an intraperitoneal injection of PQ, and the others were intraperitoneally injected with the same volume of saline. All piglets were sacrificed on day 21 for plasma and liver sample collection. The results showed that dietary Si supplementation mitigated PQ-induced liver damage, as proven by the reduction in liver pathological changes and plasma activity of alanine transaminase and aspartate transaminase. Si also improved superoxide dismutase and glutathione peroxidase activities and total antioxidant capacity, as well as decreased malondialdehyde and hydrogen peroxide concentration in the liver, which were closely related to the activation of the nuclear factor-erythroid 2-related factor 2 signaling pathway. Meanwhile, Si reduced tumor necrosis factor-α and interleukin-8 production and their transcript levels as well as abrogated the overactivation of nuclear factor-κB induced by PQ. Importantly, Si improved mitochondrial function by maintaining mitochondrial energetics and mitochondrial dynamics, which was indicated by the elevated activity of mitochondrial complexes I and V and adenosine triphosphate content, decreased expression of dynamin 1 protein, and increased expression of mitofusin 2 protein. Moreover, Si inhibited excessive hepatic apoptosis by regulating the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated-X-protein signaling pathway. Taken together, these results indicated that Si potentially mitigated PQ-induced hepatic oxidative insults by improving antioxidant capacity and mitochondrial function and inhibiting inflammation and cell apoptosis in weaned piglets.

Dataset Information

Astaxanthin alleviated ethanol-induced liver injury by inhibition of oxidative stress and inflammatory responses via blocking of STAT3 activity.

Publications

Astaxanthin alleviated ethanol-induced liver injury by inhibition of oxidative stress and inflammatory responses via blocking of STAT3 activity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets