Renal arterial resistance index among subjects with liver cirrhosis in a Nigerian population

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 Spraque-Dawley 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-α, gene expression of transforming growth factor-β1, collagen type 1a1, TNF-α, IL-6, IL-1β, 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.

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Camel milk and bee honey regulate profibrotic cytokine gene transcripts in liver cirrhosis induced by carbon tetrachloride

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2015-0596 ◽

2016 ◽

Vol 94 (11) ◽

pp. 1141-1150 ◽

Cited By ~ 11

Author(s):

Kadry Sadek ◽

Doha Beltagy ◽

Ebeed Saleh ◽

Reham Abouelkhair

Keyword(s):

Liver Cirrhosis ◽

Carbon Tetrachloride ◽

Antioxidant Properties ◽

Resistance Index ◽

Camel Milk ◽

Male Rats ◽

Protective Effects ◽

Cytokine Gene ◽

Glucose Levels ◽

Gene Transcripts

The lack of studies regarding the mechanism of the protective effects of camel milk and bee honey against hepatotoxic compounds led us to perform this study. Thirty-six male rats were divided into two main groups. The first group (n = 9) comprised control non-cirrhotic rats. The rats of the second group (n = 27) were administered carbon tetrachloride (CCl4) by intraperitoneal injection to induce liver cirrhosis. The cirrhotic rats were then divided into three equal subgroups, each comprising nine animals, as follows: (i) cirrhotic rats, (ii) cirrhotic rats treated with camel milk, and (iii) cirrhotic rats treated with camel milk and bee honey. The present findings revealed that CCl4 elevated the activities of liver enzymes, blood glucose levels, non-esterified fatty acids (NEFA) in the serum and glycogen content in the liver. On the other hand, CCl4 significantly decreased phosphorylase activity in the liver tissue and significantly increased carbohydrate intolerance and insulin resistance index (HOMA-IR). Moreover, CCl4 induced a significant increase in oxidative stress, along with increased expression of the profibrotic cytokine genes TNF-α and TGF-β. However, camel milk either alone or in combination with bee honey ameliorated these toxic actions. The antioxidant properties of these protective agents and their effects of downregulating certain procirrhotic cytokine gene transcripts underlie this protection.

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