Protective effects of fucoidan against ethanol-induced liver injury through maintaining mitochondrial function and mitophagy balance in rats

Zhang, Zhihong; Liu, Shuang; Zhao, Hui; Liu, Ying; Xue, Meilan; Zhang, Huaqi; Qiu, Xia; Sun, Zhongyang; Liang, Hui

doi:10.1039/d0fo03220d

Cited by 37 publications

(19 citation statements)

References 66 publications

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“…As discovered by Zhao et al, in the livers of alcohol-fed rats, decreased antioxidant enzymes, such as GSH and CAT, increased lipid peroxidation products, and lipid metabolic disorders were observed. Fucoidan pretreatment restored the normal levels of antioxidant enzymes, alleviated oxidative damage, and improved the lipid metabolic disorders [ 41 ], indicating that fucoidan prevented the occurrence of FALD to a certain extent. Ma et al, reported the therapeutic effect of resveratrol on rat FALD and found that ROS levels in the livers of FALD rats were controlled after the administration of resveratrol, which in turn improved FALD [ 42 ].…”

Section: Mitochondrial Dysfunction and Chronic Liver Diseasementioning

confidence: 99%

“…Morphological structure Mitochondria are swollen, the inner membrane is destroyed, the cristae have disappeared, and the membrane potential is decreased. [41,43,45,46] Energy metabolism Fatty acids have accumulated and ATP synthesis is decreased. [39][40][41][42][43]46] ROS GSH and SOD are decreased, and ROS is increased.…”

Section: Types Of Dysfunction Specific Characterization Referencesmentioning

confidence: 99%

“…[41,43,45,46] Energy metabolism Fatty acids have accumulated and ATP synthesis is decreased. [39][40][41][42][43]46] ROS GSH and SOD are decreased, and ROS is increased. [39,41,42,[44][45][46][47] mtDNA mtDNA copy number is reduced.…”

Section: Types Of Dysfunction Specific Characterization Referencesmentioning

confidence: 99%

“…[39][40][41][42][43]46] ROS GSH and SOD are decreased, and ROS is increased. [39,41,42,[44][45][46][47] mtDNA mtDNA copy number is reduced.…”

Section: Types Of Dysfunction Specific Characterization Referencesmentioning

confidence: 99%

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Mitochondrial Dysfunction and Chronic Liver Disease

Zhao

Qin

et al. 2022

CIMB

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Mitochondria are generally considered the powerhouse of the cell, a small subcellular organelle that produces most of the cellular energy in the form of adenosine triphosphate (ATP). In addition, mitochondria are involved in various biological functions, such as biosynthesis, lipid metabolism, oxidative phosphorylation, cell signal transduction, and apoptosis. Mitochondrial dysfunction is manifested in different aspects, like increased mitochondrial reactive oxygen species (ROS), mitochondrial DNA (mtDNA) damage, adenosine triphosphate (ATP) synthesis disorder, abnormal mitophagy, as well as changes in mitochondrial morphology and structure. Mitochondrial dysfunction is related to the occurrence and development of various chronic liver diseases, including hepatocellular carcinoma (HCC), viral hepatitis, drug-induced liver injury (DILI), alcoholic fatty liver (AFL), and non-alcoholic fatty liver (NAFL). In this review, we summarize and discuss the role and mechanisms of mitochondrial dysfunction in chronic liver disease, focusing on and discussing some of the latest studies on mitochondria and chronic liver disease.

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Section: Mitochondrial Dysfunction and Chronic Liver Diseasementioning

confidence: 99%

Section: Types Of Dysfunction Specific Characterization Referencesmentioning

confidence: 99%

Section: Types Of Dysfunction Specific Characterization Referencesmentioning

confidence: 99%

“…[39][40][41][42][43]46] ROS GSH and SOD are decreased, and ROS is increased. [39,41,42,[44][45][46][47] mtDNA mtDNA copy number is reduced.…”

Section: Types Of Dysfunction Specific Characterization Referencesmentioning

confidence: 99%

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Mitochondrial Dysfunction and Chronic Liver Disease

Zhao

Qin

et al. 2022

CIMB

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“…High levels of FFA in cells render the mitochondria prone to overproduction of reactive oxygen species (ROS; Zorov et al, 2014), which can lead to mitochondrial damage (Sanz et al, 2006) and aggravate hepatic lipidosis (Rector et al, 2010). Thus, timely elimination of damaged mitochondria contributes to reduction in ROS production and helps maintain lipid metabolism homeostasis (Rector et al, 2010;Zhao et al, 2021;Cioffi et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Low abundance of mitophagy markers is associated with reactive oxygen species overproduction in cows with fatty liver and causes reactive oxygen species overproduction and lipid accumulation in calf hepatocytes

Fang

Liu

Zhu

et al. 2022

Journal of Dairy Science

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Mitochondria are the main site of fatty acid oxidation and reactive oxygen species (ROS) formation. Damaged or dysfunctional mitochondria induce oxidative stress and increase the risk of lipid accumulation. During the process of mitophagy, PTEN induced kinase 1 (PINK1) accumulates on damaged mitochondria and recruits cytoplasmic Parkin to mitochondria. As an autophagy receptor protein, sequestosome-1 (p62) binds Parkin-ubiquitinated outer mitochondrial membrane proteins and microtubule-associated protein 1 light chain 3 (LC3) to facilitate degradation of damaged mitochondria. In nonruminants, clearance of dysfunctional mitochondria through the PINK1/Parkin-mediated mitophagy pathway contributes to reducing ROS production and maintaining metabolic homeostasis. Whether PINK1/Parkin-mediated mitophagy plays a similar role in dairy cow liver is not well known. Thus, the objective of this study was to investigate mitophagy status in dairy cows with fatty liver and its role in free fatty acid (FFA)-induced oxidative stress and lipid accumulation. Liver and blood samples were collected from healthy dairy cows (n = 10) and cows with fatty liver (n = 10) that had a similar number of lactations (median = 3, range = 2 to 4) and days in milk (median = 6 d, range = 3 to 9 d). Calf hepatocytes were isolated from 5 healthy newborn female Holstein calves (1 d of age, 30-40 kg). Hepatocytes were transfected with small interfering RNA targeted against PRKN for 48 h or transfected with PRKN overexpression plasmid for 36 h, followed by treatment with FFA (0.3 or 1.2 mM) for 12 h. Mitochondria were isolated from fresh liver tissue or calf hepatocytes. Serum concentrations of β-hydroxybutyrate were higher in dairy cows with fatty liver. Hepatic malondialdehyde (MDA) and hydrogen peroxide (H 2 O 2 ) were greater in cows with fatty liver. The lower protein abundance of PINK1, Parkin, p62, and LC3-II in hepatic mitochondrial fraction of dairy cows with fatty liver indicated the mitophagy was impaired. In hepatocytes, knockdown of PRKN decreased protein abundance of p62 and LC3-II in the mitochondrial fraction, and increased contents of triacylglycerol (TG), MDA, and H 2 O 2 . In addition, protein abundances of PINK1, Parkin, p62, and LC3-II were lower in the mitochondrial fraction from hepatocytes treated with 1.2 mM FFA than the hepatocytes treated with 0.3 mM FFA, whereas the content of TG, MDA, and H 2 O 2 increased. In 1.2 mM FFA-treated hepatocytes, PRKN overexpression increased protein abundance of p62 and LC3-II in the mitochondrial fraction and decreased contents of TG, MDA, and H 2 O 2 . Together, our data demonstrate that low abundance of mitophagy markers is associated with ROS overproduction in dairy cows with fatty liver and impaired mitophagy induced by a high concentration of FFA promotes ROS production and lipid accumulation in female calf hepatocytes.

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Garlic oil alleviates high triglyceride levels in alcohol‐exposed rats by inhibiting liver oxidative stress and regulating the intestinal barrier and intestinal flora

Wang

Zhang

Teng

et al. 2022

Food Science & Nutrition

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Garlic oil (GO) is a kind of natural extract extracted from garlic, which has strong antioxidant activity. This study elucidates the protective mechanism of GO against alcohol‐induced high triglyceride levels. Sixty male Sprague Dawley rats were assigned to five groups, including a control group (CON), a model group (MOD) treated with alcohol 56% v/v at 8 ml kg −1 day −1 for 2 weeks then 10 ml kg −1 day −1 for 8 weeks, a low‐dose GO group (GO‐L) given GO at 20 mg kg −1 day −1 , a high‐dose GO group (GO‐H) given GO at 40 mg kg −1 day −1 , and a positive group (POS) given diammonium glycyrrhizinate at 200 mg kg −1 day −1 . The results showed that GO could significantly reduce the serum and liver triglyceride levels caused by alcohol exposure ( p < .05). The GO‐H group significantly reduced MDA level, increased SOD and GSH‐Px levels in serum, liver, and colon ( p < .05), significantly increased the levels of Sirt1 and PGC‐1α proteins and reduced FoxO1 protein level in liver ( p < .05), and significantly increased the levels of ZO‐1 and Claudin1 proteins in the colon compared to the MOD group ( p < .05). The 16S rRNA sequencing showed that the intestinal flora of the GO‐H group was significantly changed compared with the MOD group. In summary, GO has the potential to improve high triglyceride levels in serum and liver induced by alcohol exposure, which may be related to the inhibition of oxidative stress regulation of Sirt1 and its downstream proteins, and to the restoration of the intestinal barrier and intestinal flora.

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Protective effects of fucoidan against ethanol-induced liver injury through maintaining mitochondrial function and mitophagy balance in rats

Abstract: For alcoholic liver disease (ALD), mitophagy was reported as a promising therapeutic strategy to alleviate the hepatic lesion elicited by ethanol. This study was to investigate the regulatory effects of...

Cited by 37 publications

References 66 publications

Mitochondrial Dysfunction and Chronic Liver Disease

Mitochondrial Dysfunction and Chronic Liver Disease

Low abundance of mitophagy markers is associated with reactive oxygen species overproduction in cows with fatty liver and causes reactive oxygen species overproduction and lipid accumulation in calf hepatocytes

Garlic oil alleviates high triglyceride levels in alcohol‐exposed rats by inhibiting liver oxidative stress and regulating the intestinal barrier and intestinal flora

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