Mitochondria-targeted antioxidant mitoquinone attenuates liver inflammation and fibrosis in cirrhotic rats
Küçük Resim Yok
Tarih
2020
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
American Physiological Society
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
In liver cirrhosis, oxidative stress plays a major role in promoting liver inflammation and fibrosis. Mitochondria dysregulation is responsible for excessive reactive oxygen species production. Therefore, in an experimental model of cirrhosis, we investigated the effect of mitochondria-targeted antioxidant mitoquinone. Liver cirrhosis was induced in SpraqueDawley rats by common bile duct ligation (CBDL). Mitoquinone (10 mg·kg-1 ·day-1 , oral gavage) or vehicle was administered from 3rd to 28th day after CBDL, when animals were euthanized; liver oxidative stress, inflammation, fibrosis, mitophagy were evaluated; and in vivo and ex vivo hemodynamic studies were performed. In cirrhotic rats, mitoquinone prevented liver inflammation, hepatocyte necrosis, and fibrosis at histological examination; decreased circulating TNF-?, gene expression of transforming growth factor-?1, collagen type 1a1, TNF-?, IL-6, IL-1?, tissue inhibitor of metalloproteinase-1, matrix metalloproteinase (MMP)-2, and MMP-13; and reduced hepatic oxidative stress, as shown by reduced oxidative carbonylation of the proteins, by modulating antioxidants catalase, Mn superoxide dismutase, and Cu/Zn superoxide dismutase. Furthermore, mitoquinone attenuated apoptosis by reducing hepatic protein expression of cleaved caspase-3. A selective removal of dysfunctional mitochondria was improved by mitoquinone, as shown by the increase in Parkin translocation to mitochondria. Treatment with mitoquinone normalized the weight of the spleen; however, it increased portal blood flow and reduced splenic artery intrahepatic resistance, suggesting an effect on resistance index. Mitochondria-targeted antioxidant mitoquinone improves liver inflammation and fibrosis in cirrhotic rats by reducing hepatic oxidative stress, preventing apoptosis, and promoting removal of dysfunctional mitochondria. Therefore, it may represent a promising strategy for the prevention and treatment of liver cirrhosis. © 2020 the American Physiological Society.
Açıklama
Anahtar Kelimeler
Liver cirrhosis, Mitochondria dysfunction, Mitoquinone, Oxidative stress, antioxidant, catalase, collagen, collagen type 1a1, collagenase 3, copper zinc superoxide dismutase, gelatinase A, interleukin 1beta, interleukin 6, liver protein, manganese superoxide dismutase, mitoquinone, parkin, reactive oxygen metabolite, tissue inhibitor of metalloproteinase 1, transforming growth factor beta1, tumor necrosis factor, unclassified drug, antioxidant, cytokine, mitoquinone, organophosphorus compound, ubiquinone, animal experiment, animal model, animal tissue, antioxidant activity, apoptosis, Article, biochemical analysis, cell death, disorders of mitochondrial functions, ex vivo study, gene expression, hemodynamics, hepatitis, histology, histopathology, in vivo study, liver cell, liver fibrosis, liver weight, male, mitochondrion, mitophagy, nonhuman, oxidative stress, portal vein blood flow, priority journal, protein carbonylation, protein expression, rat, spleen artery, spleen weight, animal, blood, drug effect, fibrosis, hepatitis, liver, liver cirrhosis, liver mitochondrion, pathology, spleen, Sprague Dawley rat, Animals, Antioxidants, Apoptosis, Cytokines, Fibrosis, Hemodynamics, Hepatitis, Liver, Liver Cirrhosis, Male, Mitochondria, Liver, Organophosphorus Compounds, Oxidative Stress, Rats, Rats, Sprague-Dawley, Spleen, Ubiquinone
Kaynak
American Journal of Physiology - Gastrointestinal and Liver Physiology
WoS Q Değeri
Scopus Q Değeri
Q1
Cilt
318
Sayı
2
