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Astaxanthin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy via the ROS/MAPK Pathway in Mice.

Li J, Wang F, Xia Y, Dai W, Chen K, Li S, Liu T, Zheng Y, Wang J, Lu W, Zhou Y, Yin Q, Lu J, Zhou Y, Guo C - Mar Drugs (2015)

Bottom Line: The mice received ASX at different doses (30 mg/kg or 60 mg/kg) for 14 days.ASX reduced the release of ROS and cytokines leading to inhibition of apoptosis and autophagy via down-regulation of the activated phosphorylation of related proteins in the MAPK family, such as P38 MAPK, JNK and ERK in this model of hepatic IR injury.Apoptosis and autophagy caused by hepatic IR injury were inhibited by ASX following a reduction in the release of ROS and inflammatory cytokines, and the relationship between the two may be associated with the inactivation of the MAPK family.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. sealjj@126.com.

ABSTRACT

Background: Hepatic ischemia reperfusion (IR) is an important issue in complex liver resection and liver transplantation. The aim of the present study was to determine the protective effect of astaxanthin (ASX), an antioxidant, on hepatic IR injury via the reactive oxygen species/mitogen-activated protein kinase (ROS/MAPK) pathway.

Methods: Mice were randomized into a sham, IR, ASX or IR + ASX group. The mice received ASX at different doses (30 mg/kg or 60 mg/kg) for 14 days. Serum and tissue samples at 2 h, 8 h and 24 h after abdominal surgery were collected to assess alanine aminotransferase (ALT), aspartate aminotransferase (AST), inflammation factors, ROS, and key proteins in the MAPK family.

Results: ASX reduced the release of ROS and cytokines leading to inhibition of apoptosis and autophagy via down-regulation of the activated phosphorylation of related proteins in the MAPK family, such as P38 MAPK, JNK and ERK in this model of hepatic IR injury.

Conclusion: Apoptosis and autophagy caused by hepatic IR injury were inhibited by ASX following a reduction in the release of ROS and inflammatory cytokines, and the relationship between the two may be associated with the inactivation of the MAPK family.

No MeSH data available.


Related in: MedlinePlus

ASX had no injurious effects on liver tissue. (A) ALT and AST were expressed as the mean ± SD of 8 mice per group; (B) western blots of the expression of Bcl-2, Bax, Beclin-1 and LC3 are shown by gray bands; (C) the mRNA expression of Bcl-2, Bax, Beclin-1 and LC3 was assessed by real time PCR. The experiments were repeated three times and data are presented as the mean ± SD. * p < 0.05 for ASX (30 mg/kg) vs. oil; (D) representative hematoxylin and eosin (HE) stained sections of liver shown by digital microscopy. Original magnifications: 200×.
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marinedrugs-13-03368-f001: ASX had no injurious effects on liver tissue. (A) ALT and AST were expressed as the mean ± SD of 8 mice per group; (B) western blots of the expression of Bcl-2, Bax, Beclin-1 and LC3 are shown by gray bands; (C) the mRNA expression of Bcl-2, Bax, Beclin-1 and LC3 was assessed by real time PCR. The experiments were repeated three times and data are presented as the mean ± SD. * p < 0.05 for ASX (30 mg/kg) vs. oil; (D) representative hematoxylin and eosin (HE) stained sections of liver shown by digital microscopy. Original magnifications: 200×.

Mentions: Before validation of the protective effects of ASX on hepatic IR injury, we first determined the influence of ASX on normal liver tissue. The same number of mice were given the same volume of saline, olive oil or ASX (30 mg/kg or 60 mg/kg) for 14 days, respectively. Serum and liver tissues were obtained from the mice to examine liver function, pathology and markers related to damage (Bcl-2, Bax, Beclin-1 and LC3) using biochemical methods, PCR detection and western blot. The results showed that the expression of serum liver enzymes in the four groups was close to normal levels (Figure 1A), while at the gene and protein levels, differences in relevant autophagic and apoptotic indicators were not obvious (Figure 1B,C). Finally, we identified pathological and morphological changes in the ASX groups. The cell structures showed small disturbances, which may have been due to the influence of drug metabolism, and liver function and protein expression in the related pathways showed no significant effects (Figure 1D). Thus, ASX and olive oil had no significant effect on normal liver tissue.


Astaxanthin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy via the ROS/MAPK Pathway in Mice.

Li J, Wang F, Xia Y, Dai W, Chen K, Li S, Liu T, Zheng Y, Wang J, Lu W, Zhou Y, Yin Q, Lu J, Zhou Y, Guo C - Mar Drugs (2015)

ASX had no injurious effects on liver tissue. (A) ALT and AST were expressed as the mean ± SD of 8 mice per group; (B) western blots of the expression of Bcl-2, Bax, Beclin-1 and LC3 are shown by gray bands; (C) the mRNA expression of Bcl-2, Bax, Beclin-1 and LC3 was assessed by real time PCR. The experiments were repeated three times and data are presented as the mean ± SD. * p < 0.05 for ASX (30 mg/kg) vs. oil; (D) representative hematoxylin and eosin (HE) stained sections of liver shown by digital microscopy. Original magnifications: 200×.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4483634&req=5

marinedrugs-13-03368-f001: ASX had no injurious effects on liver tissue. (A) ALT and AST were expressed as the mean ± SD of 8 mice per group; (B) western blots of the expression of Bcl-2, Bax, Beclin-1 and LC3 are shown by gray bands; (C) the mRNA expression of Bcl-2, Bax, Beclin-1 and LC3 was assessed by real time PCR. The experiments were repeated three times and data are presented as the mean ± SD. * p < 0.05 for ASX (30 mg/kg) vs. oil; (D) representative hematoxylin and eosin (HE) stained sections of liver shown by digital microscopy. Original magnifications: 200×.
Mentions: Before validation of the protective effects of ASX on hepatic IR injury, we first determined the influence of ASX on normal liver tissue. The same number of mice were given the same volume of saline, olive oil or ASX (30 mg/kg or 60 mg/kg) for 14 days, respectively. Serum and liver tissues were obtained from the mice to examine liver function, pathology and markers related to damage (Bcl-2, Bax, Beclin-1 and LC3) using biochemical methods, PCR detection and western blot. The results showed that the expression of serum liver enzymes in the four groups was close to normal levels (Figure 1A), while at the gene and protein levels, differences in relevant autophagic and apoptotic indicators were not obvious (Figure 1B,C). Finally, we identified pathological and morphological changes in the ASX groups. The cell structures showed small disturbances, which may have been due to the influence of drug metabolism, and liver function and protein expression in the related pathways showed no significant effects (Figure 1D). Thus, ASX and olive oil had no significant effect on normal liver tissue.

Bottom Line: The mice received ASX at different doses (30 mg/kg or 60 mg/kg) for 14 days.ASX reduced the release of ROS and cytokines leading to inhibition of apoptosis and autophagy via down-regulation of the activated phosphorylation of related proteins in the MAPK family, such as P38 MAPK, JNK and ERK in this model of hepatic IR injury.Apoptosis and autophagy caused by hepatic IR injury were inhibited by ASX following a reduction in the release of ROS and inflammatory cytokines, and the relationship between the two may be associated with the inactivation of the MAPK family.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. sealjj@126.com.

ABSTRACT

Background: Hepatic ischemia reperfusion (IR) is an important issue in complex liver resection and liver transplantation. The aim of the present study was to determine the protective effect of astaxanthin (ASX), an antioxidant, on hepatic IR injury via the reactive oxygen species/mitogen-activated protein kinase (ROS/MAPK) pathway.

Methods: Mice were randomized into a sham, IR, ASX or IR + ASX group. The mice received ASX at different doses (30 mg/kg or 60 mg/kg) for 14 days. Serum and tissue samples at 2 h, 8 h and 24 h after abdominal surgery were collected to assess alanine aminotransferase (ALT), aspartate aminotransferase (AST), inflammation factors, ROS, and key proteins in the MAPK family.

Results: ASX reduced the release of ROS and cytokines leading to inhibition of apoptosis and autophagy via down-regulation of the activated phosphorylation of related proteins in the MAPK family, such as P38 MAPK, JNK and ERK in this model of hepatic IR injury.

Conclusion: Apoptosis and autophagy caused by hepatic IR injury were inhibited by ASX following a reduction in the release of ROS and inflammatory cytokines, and the relationship between the two may be associated with the inactivation of the MAPK family.

No MeSH data available.


Related in: MedlinePlus