Antioxidant and anti-inflammatory action of melatonin in an experimental model of secondary biliary cirrhosis induced by bile duct ligation

Colares, Josieli Raskopf; Schemitt, Elizângela Gonçalves; Hartmann, Renata Minuzzo; Licks, Francielli; Soares, Mariana do Couto; Bosco, Adriane Dal; Marroni, Norma Possa

doi:10.3748/wjg.v22.i40.8918

Cited by 40 publications

(44 citation statements)

References 34 publications

(40 reference statements)

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“…The present study displays that quercetin treatment is capable of reducing ALT, ALP, AST, D‐BIL, and T‐BIL levels, suggesting a protective effect of quercetin in liver function and a beneficial role in alleviating hepatic fibrosis. These results corroborate the findings of previous studies (Colares et al., ; Lin et al., ), in which animals underwent BDL surgery and treatment with quercetin antioxidant. The findings of this study corroborate that the levels of MDA have a positive relationship with the increasing trend of liver fibrosis.…”

Section: Discussionsupporting

confidence: 92%

“…Recent findings propose that activated HSCs could contribute to the fibrogenic process through the secretion and stimulation of a wide range of pro‐inflammatory cytokines (Flanagan et al., ). Activating the ERK1/HIF‐1α/NF‐κB signaling pathway also enables the production pro‐inflammatory cytokines (Barta et al., ; Colares et al., ). Our results demonstrated that quercetin obstructed the effect of leptin on the activation of HSCs by the interruption of leptin signaling and the ERK1/HIF‐1α/ NF‐κB signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

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Quercetin Mitigates Hepatic Insulin Resistance in Rats with Bile Duct Ligation Through Modulation of the STAT3/SOCS3/IRS1 Signaling Pathway

Khodarahmi

Eshaghian

Safari

2019

Journal of Food Science

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Insulin resistance (IR) and inflammatory mediators are correlated with hepatic fibrosis. Quercetin is a bioflavonoid with well‐known antidiabetic and antifibrotic properties. Bile duct ligation (BDL) is a surgical model performed on animals to produce a murine model in which increased oxidative stress occurs, which results in liver fibrosis. Our study aimed to determine whether quercetin improves hepatic IR as well as hepatic fibrosis in rats experiencing BDL. Male Wistar rats were allocated to four groups according to a random pattern, including a sham group, a sham and quercetin group (30 mg/kg/day), a BDL alone group, and a BDL and quercetin group (30 mg/kg/day). Evaluation of STAT3, SOCS3, IRS1, Rac1, Rac1‐GTP, Sp1, NOX1, HIF‐1α, and ERK1 expression was performed by RT‐PCR along with the western blot analytical technique in liver tissue. The antidiabetic impact of quercetin was associated with reduction in mRNA and expression of protein in STAT3 and SOCS3, along with an increase in IRS1. The antifibrotic effect of quercetin was also determined by downregulation of mRNA or the levels of protein expression of Rac1‐GTP, Rac1, HIF‐1α, NOX1, and Sp1, along with ERK1. Our study indicates that quercetin may improve hepatic fibrosis via inhibiting ROS‐associated inflammation as well as ameliorating hepatic IR by beneficial regulation of the STAT3/SOCS3/IRS1 signaling pathway.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Quercetin Mitigates Hepatic Insulin Resistance in Rats with Bile Duct Ligation Through Modulation of the STAT3/SOCS3/IRS1 Signaling Pathway

Khodarahmi

Eshaghian

Safari

2019

Journal of Food Science

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“…Our research group has conducted studies on the effects of MLT on liver injury and diseases and found that MLT can regulate various molecular pathways such as inflammation, proliferation, apoptosis, metastasis, and autophagy in different situations …”

Section: Discussionmentioning

confidence: 99%

“…Similar results were found in rats with liver fibrosis induced by bile duct ligation, using pre-and posttreatment with brivanib alaninate, sulforaphane, astaxanthin, quercetin, and MLT. [43][44][45][46] In fact, the inhibition of this fibrogenesis pathway is a key strategy for the regulation of the differentiation and proliferation of HSC and the subsequent control of ECM deposition in diseases involving fibrogenesis.…”

Section: Discussionmentioning

confidence: 99%

Antifibrogenic effect of melatonin in rats with experimental liver cirrhosis induced by carbon tetrachloride

et al. 2018

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Background and AimLiver diseases are a major public health problem, accounting for a significant number of hospital visits and admissions and an increasing mortality rate. Melatonin (MLT) is a powerful antioxidant molecule that has been shown to be beneficial under various conditions. The objective was to evaluate the effect of MLT on experimental liver cirrhosis induced by carbon tetrachloride (CCl4) in rats.MethodsTwenty male Wistar rats (230–250 g) were divided into four groups. I: control group (CO); II: CO + MLT; III: CCl4; and IV: CCl4 + MLT. CCl4 was administered intraperitoneally (i.p.) as follows: 10 doses every 5 days, 10 doses every 4 days, and 7 doses every 3 days. MLT was administered i.p. at a dose of 20 mg/kg from the 10th week to the end of the experiment (16th week).ResultsIn the CCl4 + MLT group, we found that MLT caused a decrease in the level of F2‐isoprostanes and NQO1 expression. We also found that MLT reduced the inflammatory process as shown by decreased expressions of NF‐KB/p65 and inducible nitric oxide synthase (iNOS) and a smaller amount of inflammatory infiltrate. MLT reduced the expression of transforming growth factor beta1 (TGF‐β1), alpha‐smooth muscle actin (α‐SMA), and vascular endothelial growth factor (VEGF). Picrosirius staining showed that MLT decreases fibrosis.ConclusionMLT has a potent antifibrogenic effect, modulating the parameters of oxidative stress, angiogenesis, and inflammation.

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“…MT significantly decreased the expression of clock genes (PER1, BMAL1, CRY1 and CLOCK) as well as cAMP levels and PKA phosphorylation, consequently reducing serum bilirubin and transaminase levels, the percentage of PCNA-positive cholangiocytes and biliary hyperplasia in the cholangiocytes of BDL rats 64. After administration in vivo, MT was effective in reducing the hepatosomatic and splenosomatic indices, restoring normal levels of lipid peroxidation and antioxidant enzyme expression and inhibiting inflammation, thus decreasing liver injury and liver fibrosis in BDL-induced secondary biliary cirrhosis 65. On the other hand, MT is able to suppress the release of hypothalamic gonadotropin-releasing hormone (GnRH), a hormone that promotes cholangiocyte proliferation 65.…”

mentioning

confidence: 98%

Protective role of melatonin in early‐stage and end‐stage liver cirrhosis

Zhao

Tao

et al. 2019

J Cellular Molecular Medi

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The liver is composed of hepatocytes, cholangiocytes, Kupffer cells, sinusoidal endothelial cells, hepatic stellate cells (HSCs) and dendritic cells; all these functional and interstitial cells contribute to the synthesis and secretion functions of liver tissue. However, various hepatotoxic factors including infection, chemicals, high‐fat diet consumption, surgical procedures and genetic mutations, as well as biliary tract diseases such as sclerosing cholangitis and bile duct ligation, ultimately progress into liver cirrhosis after activation of fibrogenesis. Melatonin (MT), a special hormone isolated from the pineal gland, participates in regulating multiple physiological functions including sleep promotion, circadian rhythms and neuroendocrine processes. Current evidence shows that MT protects against liver injury by inhibiting oxidation, inflammation, HSC proliferation and hepatocyte apoptosis, thereby inhibiting the progression of liver cirrhosis. In this review, we summarize the circadian rhythm of liver cirrhosis and its potential mechanisms as well as the therapeutic effects of MT on liver cirrhosis and earlier‐stage liver diseases including liver steatosis, nonalcoholic fatty liver disease and liver fibrosis. Given that MT is an antioxidative and anti‐inflammatory agent that is effective in eliminating liver injury, it is a potential agent with which to reverse liver cirrhosis in its early stage.

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Antioxidant and anti-inflammatory action of melatonin in an experimental model of secondary biliary cirrhosis induced by bile duct ligation

Cited by 40 publications

References 34 publications

Quercetin Mitigates Hepatic Insulin Resistance in Rats with Bile Duct Ligation Through Modulation of the STAT3/SOCS3/IRS1 Signaling Pathway

Quercetin Mitigates Hepatic Insulin Resistance in Rats with Bile Duct Ligation Through Modulation of the STAT3/SOCS3/IRS1 Signaling Pathway

Antifibrogenic effect of melatonin in rats with experimental liver cirrhosis induced by carbon tetrachloride

Protective role of melatonin in early‐stage and end‐stage liver cirrhosis

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