Agomelatine protects heart and aorta against lipopolysaccharide-induced cardiovascular toxicity via inhibition of NF-kβ phosphorylation

Aşçı, Halil; Özmen, Özlem; Erzurumlu, Yalçın; Sofu, Aytül; Icten, P.; Kaynak, Mine

doi:10.1080/01480545.2019.1663209

Cited by 15 publications

(8 citation statements)

References 69 publications

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“…According to findings from previous reports, agomelatine has been shown to promote dopamine production in the prefrontal cortex and increase cell proliferation in the hippocampus of rats, as well as promote neuronal growth, cell survival and increase the level of circulating BDNF [ 35 – 37 ]. Owing to its antioxidant and anti-inflammatory properties, agomelatine has also been shown to exert a number of effects in other tissues and systems, such as the cardiovascular system, liver and kidney [ 38 – 40 ] and results from in vitro experiments have shown that agomelatine can reduce oxidative stress by inhibiting ROS production [ 41 ]. Additional effects of agomelatine include protection of myocardial ischemia reperfusion injury by enhancing GSK-3β phosphorylation [ 42 ] and repair of the blood−brain barrier through inhibiting the infiltration of macrophages into brain tissue [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Agomelatine rescues lipopolysaccharide-induced neural injury and depression-like behaviors via suppression of the Gαi-2-PKA-ASK1 signaling pathway

Lan

Zhang

et al. 2022

J Neuroinflammation

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Background Agomelatine has been shown to be effective in the treatment of depression, but the molecular mechanisms underlying its antidepressant effects have yet to be elucidated. Identification of these molecular mechanisms would not only offer new insights into the basis for depression but also provide the foundation for the development of novel treatments for this disorder. Methods Intraperitoneal injection of LPS was used to induce depression-like behaviors in rats. The interactions of the 5-HT2C reporter and Gαi-2 were verified by immunoprecipitation or immunofluorescence assay. Inflammatory related proteins, autophagy related proteins and apoptosis markers were verified by immunoblotting or immunofluorescence assay. Finally, electron microscopy analysis was used to observe the synapse and ultrastructural pathology. Results Here, we found that the capacity for agomelatine to ameliorate depression and anxiety in a lipopolysaccharide (LPS)-induced rat model of depression was associated with an alleviation of neuroinflammation, abnormal autophagy and neuronal apoptosis as well as the promotion of neurogenesis in the hippocampal dentate gyrus (DG) region of these rats. We also found that the 5-HT2C receptor is coupled with G alphai (2) (Gαi-2) protein within hippocampal neurons and, agomelatine, acting as a 5-HT2C receptor antagonist, can up-regulate activity of the Gαi-2-cAMP-PKA pathway. Such events then suppress activation of the apoptosis signal-regulating kinase 1 (ASK1) pathway, a member of the mitogen-activated protein kinase (MAPK) family involved in pathological processes of many diseases. Conclusion Taken together, these results suggest that agomelatine plays a neuroprotective role in regulating neuroinflammation, autophagy disorder and apoptosis in this LPS-induced rat model of depression, effects which are associated with the display of antidepressant behaviors. These findings provide evidence for some of the potential mechanisms for the antidepressant effects of agomelatine. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Agomelatine rescues lipopolysaccharide-induced neural injury and depression-like behaviors via suppression of the Gαi-2-PKA-ASK1 signaling pathway

Lan

Zhang

et al. 2022

J Neuroinflammation

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“…LPS systemic administration can induce several organ disorder including heart damage [ 11 ]. Also it was shown that single dose of LPS induced a systemic inflammation and cardiovascular toxicity [ 12 ]. LPS exposure is thought to cause severe stress in cardiomyocytes, resulting in a loss of myocardial integrity due to a combination of oxygen deficiency, calcium overload, and the overproduction of free radicals [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

A protective effect of curcumin on cardiovascular oxidative stress indicators in systemic inflammation induced by lipopolysaccharide in rats

Ahmadabady

Beheshti

Shahidpour

et al. 2021

Biochemistry and Biophysics Reports

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“…A growing body of literature suggested that oxidative/nitrosative stress disrupts the architecture of cardio‐myocytes during sepsis 3,6,9 . The loss of structural integrity of the cardio‐myocytes is reflected by abnormal serum levels of biochemical markers including aspartate aminotransferase (AST), cardiac muscle creatinine kinase (CK‐MB), troponin T (cTn‐T), lactate dehydrogenase (LDH), and B‐type natriuretic peptide (BNP) 9,37 . Previous studies revealed a significant disturbance in these biochemical factors, associated with a reduction in antioxidant capacity in LPS‐injured hearts 9,37 …”

Section: Discussionmentioning

confidence: 99%

Zataria multiflora and its constituent, carvacrol, counteract sepsis‐induced aortic and cardiac toxicity in rat: Involvement of nitric oxide and oxidative stress

Hosseini

Arab

Beheshti

et al. 2023

Anim Models and Exp Med

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Background: Zataria multiflora and carvacrol showed various pharmacological properties including anti-inflammatory and anti-oxidant effects. However, up to now no studies have explored its potential benefits in ameliorating sepsis-induced aortic and cardiac injury. Thus, this study aimed to investigate the effects of Z. multiflora and carvacrol on nitric oxide (NO) and oxidative stress indicators in lipopolysaccharide (LPS)-induced aortic and cardiac injury.Methods: Adult male Wistar rats were assigned to: Control, lipopolysaccharide (LPS)(1 mg/kg, intraperitoneal (i.p.)), and Z. multiflora hydro-ethanolic extract (ZME, 50-200 mg/kg, oral)-and carvacrol (25-100 mg/kg, oral)-treated groups. LPS was injected daily for 14 days. Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration. At the end of the study, the levels of malondialdehyde (MDA), NO, thiols, and antioxidant enzymes were evaluated. Results:Our findings showed a significant reduction in the levels of superoxide dismutase (SOD), catalase (CAT), and thiols in the LPS group, which were restored by ZME and carvacrol. Furthermore, ZME and carvacrol decreased MDA and NO in cardiac and aortic tissues of LPS-injected rats. Conclusions:The results suggest protective effects of ZME and carvacrol on LPSinduced cardiovascular injury via improved redox hemostasis and attenuated NO production. However, additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.

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Agomelatine protects heart and aorta against lipopolysaccharide-induced cardiovascular toxicity via inhibition of NF-kβ phosphorylation

Cited by 15 publications

References 69 publications

Agomelatine rescues lipopolysaccharide-induced neural injury and depression-like behaviors via suppression of the Gαi-2-PKA-ASK1 signaling pathway

Agomelatine rescues lipopolysaccharide-induced neural injury and depression-like behaviors via suppression of the Gαi-2-PKA-ASK1 signaling pathway

A protective effect of curcumin on cardiovascular oxidative stress indicators in systemic inflammation induced by lipopolysaccharide in rats

Zataria multiflora and its constituent, carvacrol, counteract sepsis‐induced aortic and cardiac toxicity in rat: Involvement of nitric oxide and oxidative stress

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