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

Hu, Chenxia; Zhao, Lingfei; Tao, Jingjing; Li, Lanjuan

doi:10.1111/jcmm.14634

Cited by 37 publications

(31 citation statements)

References 87 publications

(176 reference statements)

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“…Melatonin (MLT), N-acetyl-5-methoxytryptamine, is a hormone synthesized by the pineal gland, which is produced rhythmically and is inhibited by light[ 15 , 16 ]. The antioxidant effect of MLT is related to its amphiphilic chemical structure, which facilitates its crossing through biological barriers and allows activity in both aqueous and lipid environments[ 15 , 17 ]. The numerous attributes of MLT include antioxidant capacity and anti-inflammatory and immunomodulatory effects[ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats

Colares¹,

Hartmann²,

Schemitt³

et al. 2022

WJG

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BACKGROUND Cirrhosis is an important health problem characterized by a significant change in liver parenchyma. In animals, this can be reproduced by an experimental model of bile duct ligation (BDL). Melatonin (MLT) is a physiological hormone synthesized from serotonin that has been studied for its beneficial properties, including its antioxidant potential. AIM To evaluate MLT’s effects on oxidative stress, the inflammatory process, and DNA damage in an experimental model of secondary biliary cirrhosis. METHODS Male Wistar rats were divided into 4 groups: Control (CO), CO + MLT, BDL, and BDL + MLT. MLT was administered (20 mg/kg) daily beginning on day 15 after biliary obstruction. On day 29 the animals were killed. Blood samples, liver tissue, and bone marrow were collected for further analysis. RESULTS BDL caused changes in biochemical and histological parameters and markers of inflammatory process. Thiobarbituric acid (0.46 ± 0.01) reactive substance levels, superoxide dismutase activity (2.30 ± 0.07) and nitric oxide levels (2.48 ± 0.36) were significantly lower ( P < 0.001) n the groups that received MLT. DNA damage was also lower ( P < 0.001) in MLT-treated groups (171.6 ± 32.9) than the BDL-only group (295.5 ± 34.8). Tissue damage and the expression of nuclear factor kappa B, interleukin-1β, Nrf2, NQO1 and Hsp70 were significantly lower in animals treated with MLT ( P < 0.001). CONCLUSION When administered to rats with BDL-induced secondary biliary cirrhosis, MLT effectively restored the evaluated parameters.

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Section: Introductionmentioning

confidence: 99%

Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats

Colares¹,

Hartmann²,

Schemitt³

et al. 2022

WJG

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“…On its side, IL-6 and TNF-α are important players of the inflammatory response [ 67 , 68 ]. It has been suggested that melatonin has a beneficial therapeutic value in the treatment of inflammation in different tissues [ 69 , 70 ], including the pancreas [ 71 ]. Our present results are in agreement with those previous observations and have shown that melatonin modulated the levels of proinflammatory mediators in PSC subjected to hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Modulates the Antioxidant Defenses and the Expression of Proinflammatory Mediators in Pancreatic Stellate Cells Subjected to Hypoxia

et al. 2021

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Pancreatic stellate cells (PSC) play a major role in the formation of fibrotic tissue in pancreatic tumors. On its side, melatonin is a putative therapeutic agent for pancreatic cancer and inflammation. In this work, the actions of melatonin on PSC subjected to hypoxia were evaluated. Reactive oxygen species (ROS) generation reduced (GSH) and oxidized (GSSG) levels of glutathione, and protein and lipid oxidation were analyzed. The phosphorylation of nuclear factor erythroid 2-related factor (Nrf2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), and the regulatory protein nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκBα) was studied. The expression of Nrf2-regulated antioxidant enzymes, superoxide dismutase (SOD) enzymes, cyclooxygenase 2 (COX-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also studied. Total antioxidant capacity (TAC) was assayed. Finally, cell viability was studied. Under hypoxia and in the presence of melatonin generation of ROS was observed. No increases in the oxidation of proteins or lipids were detected. The phosphorylation of Nrf2 and the expression of the antioxidant enzymes catalytic subunit of glutamate-cysteine ligase, catalase, NAD(P)H-quinone oxidoreductase 1, heme oxygenase-1, SOD1, and of SOD2 were augmented. The TAC was increased. Protein kinase C was involved in the effects of melatonin. Melatonin decreased the GSH/GSSG ratio at the highest concentration tested. Cell viability dropped in the presence of melatonin. Finally, melatonin diminished the phosphorylation of NF-kB and the expression of COX-2, IL-6, and TNF-α. Our results indicate that melatonin, at pharmacological concentrations, modulates the red-ox state, viability, and the expression of proinflammatory mediators in PSC subjected to hypoxia.

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“…Therefore, it attenuates the activation of HSCs and the proliferation of fibrogenic effector cells, ultimately reducing ECM deposition. Potentially, re-establishment of the light/dark cycle and the circadian rhythm may increase the endogenous melatonin level while improving the therapeutic effects of the indoleamine in reversing the progression of fibrosis (43).…”

Section: Discussionmentioning

confidence: 99%

Blood melatonin level can serve as a potential biomarker for prostate and hepatocellular carcinomas

et al. 2021

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Many systemic functions display circadian rhythms driven by an endogenous mechanism that is regulated by circadian-related genes and these gene expressions control a central clock in the brain and subordinate clocks in peripheral tissues. However, modern life has introduced environmental factors that often interfere with natural circadian rhythms. Importantly, circadian disruption has been identified as an independent risk factor of cancers. Melatonin is a major circadian rhythm regulator. In cancer patients, the rhythm of melatonin is often disrupted and its level is also reduced. These changes of melatonin impair its antioxidant and circadian regulatory functions on cells and tissues making them more susceptible to mutations and cancer initiation. In this context, the objectives of this study are to evaluate the sleep quality and blood levels of melatonin in patients with either prostate cancer (PC) or hepatocarcinoma (HCC) with the intent of using its levels as a potential biomarker of the cancers. The study involved 20 PC and 18 HCC patients, and 26 healthy volunteers. All blood samples were collected in the early morning, at 07:00 hours. Comparative sleep quality between PC, HCC patients and control subjects was acessed with a questionnaire, and melatonin and vitamin D were measured using conventional assays. The results revealed that patients with the worse sleep quality also had lower values of melatonin and vitamin D compared to control subjects. Notably, expression of melatonin-synthesizing enzymes and specific clock genes (PER, CRY and BMAL1) were significantly reduced and associated with worse prognosis in PC and HCC patients. These findings are consistent with the results of previous studies and suggest that disruption of the circadian rhythms, associated with changes in the light:dark cycle, has consequences for the maintenance of systemic health. We suggest that supplementation of melatonin and vitamin D may represent the important therapeutic strategies for patients with solid tumors for the purpose of improving their sleep quality and recuperative capacity.

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

Cited by 37 publications

References 87 publications

Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats

Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats

Melatonin Modulates the Antioxidant Defenses and the Expression of Proinflammatory Mediators in Pancreatic Stellate Cells Subjected to Hypoxia

Blood melatonin level can serve as a potential biomarker for prostate and hepatocellular carcinomas

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