Melatonin prevents secondary intra-abdominal hypertension in rats possibly through inhibition of the p38 MAPK pathway

Chang, Mingtao; Li, Yang; Liu, Dong; Zhang, Lianyang; Zhang, Honggang; Tang, Hao; Zhang, Huayu

doi:10.1016/j.freeradbiomed.2016.06.001

Cited by 7 publications

(5 citation statements)

References 71 publications

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“…A large amount of data obtained from both human and rodent studies have provided support for the use of melatonin to treat hypertension, heart failure, doxorubicin‐induced cardiotoxicity, atherosclerosis, cardiac damage caused by diabetes and cardiac hypertrophy induced by hyperthyroidism . However, whether melatonin protects against pressure overload‐induced cardiac hypertrophy and the underlying mechanisms remain elusive.…”

Section: Discussionmentioning

confidence: 99%

Melatonin protects against the pathological cardiac hypertrophy induced by transverse aortic constriction through activating PGC‐1β: In vivo and in vitro studies

Zhai

Liu

Zhang

et al. 2017

Journal of Pineal Research

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Melatonin, a circadian molecule secreted by the pineal gland, confers a protective role against cardiac hypertrophy induced by hyperthyroidism, chronic hypoxia, and isoproterenol. However, its role against pressure overload-induced cardiac hypertrophy and the underlying mechanisms remains elusive. In this study, we investigated the pharmacological effects of melatonin on pathological cardiac hypertrophy induced by transverse aortic constriction (TAC). Male C57BL/6 mice underwent TAC or sham surgery at day 0 and were then treated with melatonin (20 mg/kg/day, via drinking water) for 4 or 8 weeks. The 8-week survival rate following TAC surgery was significantly increased by melatonin. Melatonin treatment for 8 weeks markedly ameliorated cardiac hypertrophy. Compared with the TAC group, melatonin treatment for both 4 and 8 weeks reduced pulmonary congestion, upregulated the expression level of α-myosin heavy chain, downregulated the expression level of β-myosin heavy chain and atrial natriuretic peptide, and attenuated the degree of cardiac fibrosis. In addition, melatonin treatment slowed the deterioration of cardiac contractile function caused by pressure overload. These effects of melatonin were accompanied by a significant upregulation in the expression of peroxisome proliferator-activated receptor-gamma co-activator-1 beta (PGC-1β) and the inhibition of oxidative stress. In vitro studies showed that melatonin also protects against angiotensin II-induced cardiomyocyte hypertrophy and oxidative stress, which were largely abolished by knocking down the expression of PGC-1β using small interfering RNA. In summary, our results demonstrate that melatonin protects against pathological cardiac hypertrophy induced by pressure overload through activating PGC-1β.

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Section: Discussionmentioning

confidence: 99%

Melatonin protects against the pathological cardiac hypertrophy induced by transverse aortic constriction through activating PGC‐1β: In vivo and in vitro studies

Zhai

Liu

Zhang

et al. 2017

Journal of Pineal Research

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“…In order to explore a more effective and safe treatment for transplant rejection, we used MT to treat corneal transplant mice to study its potential therapeutic effects and underlying mechanisms. During these experiments, the mice were intraperitoneally injected with 50 mg/kg MT, as described previously ( Chang et al, 2016 ). Our results are the first to demonstrate that MT promotes corneal allograft survival.…”

Section: Discussionmentioning

confidence: 99%

Treatment With Melatonin After Corneal Graft Attenuates Rejection

et al. 2021

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Background: Immunologic graft rejection is the main complication of corneal transplants. This study aimed to investigate the effect of melatonin (MT) on the rejection of corneal transplantation.Methods: Corneal allografts were performed by grafting corneas from BALB/C mice to C57BL/6 hosts. MT (50 mg/kg) was intraperitoneally injected into the hosts every day from the day of transplantation. The survival of grafts was observed by slit lamp biomicroscopy, and inflammatory cell infiltration was detected by hematoxylin and eosin staining and immunohistochemistry. The balance of Teff and Treg immune cells in draining lymph nodes (DLNs) was detected by flow cytometry. The levels of cytokines related to the grafts and DLNs were detected using real-time fluorescence quantitative PCR. Additionally, we used the mouse macrophage line RAW264.7 to study the effect of MT on the activation of NLRP3 inflammatory body.Results: MT treatment improved the graft survival rate, reduced inflammatory cell infiltration in the graft, decreased the percentage of Th1/Th17 cells in the DLNs, and increased the percentage of Treg cells. Melatonin inhibited the activation of the NLRP3 inflammasome, thereby reducing the expression of IL-1β and other related proinflammatory cytokines such as MCP-1, MIP-1, NLRP3, ASC, TNF-a and VEGF-A (all p < 0.05).Conclusion: Our study demonstrates that MT promotes the survival of mouse corneal grafts by inhibiting NLRP3-mediated immune regulation, reducing immune cell activation and cell migration, and inhibiting the production of inflammatory-related cytokines. Treatment with MT might provide a potential clinical therapeutic target for corneal transplantation.

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“…The P38-mitogen-activated protein kinase (MAPK) functions in various signaling pathways (Wang et al, 2016), and plays a critical role in neurodegenerative diseases as well as inflammatory response as a pain regulator (Lin et al, 2014). It has been determined in rats that p38 MAPK signaling pathway functions in the prevention of intra-abdominal hypertension (Chang et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Combination of Dexmedetomidine and Tramadol in Patient-Controlled Intravenous Analgesia Strengthens Sedative Effect in Pregnancy-Induced Hypertension

Zhang

Zhao

et al. 2021

Front. Pharmacol.

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Objective: The aim of the present study is to explore the combination of dexmedetomidine (DXM) and tramadol (TMD) on sedative effect in patients with pregnancy-induced hypertension (PIH).Methods: A total of 356 patients with pregnancy-induced hypertension (PIH) were randomly divided into three groups: DXM, TMD and DXM + TMD groups. These patients were treated with different doses of DXM, TMD or combination of DXM and TMD by a patient-controlled intravenous injection device. The scores of static pain and dynamic pain, sedation degree, and adverse reaction were recorded. The plasma levels of inflammatory mediators IL-10 and C-reactive protein (CRP), and the serum level of p-p38-MAPK were evaluated.Results: It was found that administration with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg result in stronger sedative effect than single administration with DXM or TMD. The mean arterial pressure (MAP) and heart rate (HR) of patients with PIH were decreased with the combinational treatment of DXM and TMD. Interestingly, the PIH patients injected with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg showed stronger sedative effect. In addition, the plasma level of level of IL-10 was increased and CRP decreased. The serum level of p-p38/MAPK was decreased.Conclusion: Taken together, our study indicates that combination of DXM and TMD effectively lowers blood pressure and reduces inflammation through increasing the level of IL-10, reducing CRP and inhibiting p-p38/MAPK in patients with PIH. This study suggests that the combination of DXM and TMD could be an anesthetic choice in the management of PIH.

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Melatonin prevents secondary intra-abdominal hypertension in rats possibly through inhibition of the p38 MAPK pathway

Cited by 7 publications

References 71 publications

Melatonin protects against the pathological cardiac hypertrophy induced by transverse aortic constriction through activating PGC‐1β: In vivo and in vitro studies

Melatonin protects against the pathological cardiac hypertrophy induced by transverse aortic constriction through activating PGC‐1β: In vivo and in vitro studies

Treatment With Melatonin After Corneal Graft Attenuates Rejection

Combination of Dexmedetomidine and Tramadol in Patient-Controlled Intravenous Analgesia Strengthens Sedative Effect in Pregnancy-Induced Hypertension

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