Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction

Saral, Sinan; Topçu, Atilla; Alkanat, Mehmet; Mercantepe, Tolga; Akyıldız, Kerimali; Yıldız, Lamiye; Tümkaya, Levent; Yazıcı, Zihni Açar; Yılmaz, Adnan

doi:10.1016/j.bbr.2021.113290

Cited by 20 publications

(3 citation statements)

References 39 publications

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“…The MDA levels were significantly higher in the rats that received Cisplatin as a single dose only than the healthy control group, as illustrated in Figure 1. Likewise, in the Cisplatin group the IL-1β levels were significantly higher than the healthy control group, this finding is consistent with several studies attributed to Cisplatin induced retinal toxicity, hepatic toxicity, and cognitive dysfunction respectively in rat models (29)(30)(31) . In this study, the histological examination of the retina of the rat that received a Cisplatin injection showed a degeneration of retinal layers with the formation of gliosis as shown in Figure 8a, such finding also occurred after injecting IL-1β into the retina and induced a retinopathy as a result of oxidative stress and depletion of the anti-oxidant enzymes which end with accelerating the apoptosis process in the retinal microvasculature as mentioned in the previous research (32) .…”

Section: Discussionsupporting

confidence: 90%

Ameliorating Effect of Azilsartan on Cisplatin -Induced Ocular Toxicity in Male Rats

Mahmood,

Noor Majid Raheem Kareem1

2023

IJPS

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Objective: To evaluate the protective effect of Azilsartan against Cisplatin-induced ocular damage by ameliorating the oxidative stress and inflammation status, as well as to compare two different doses of Azilsartan to the Resveratrol. Fifty-six male Wister albino-rats, weighing 270±30 g. The rats were allocated at random into seven groups (n=8 per group), as follows: Group 1 (Healthy control) was given 0.5% CMC orally for the 14 days. Group 2 (Positive control) was given a single injection of 7mg/kg Cisplatin intraperitoneally and then 0.5% CMC orally for the following 14 days. Group 3 was given 3.5mg/kg Azilsartan orally for the following 14 days. Group 4 was given 7mg/kg Azilsartan orally for the following 14 days. Group 5 was given a single injection of 7mg/kg Cisplatin intraperitoneally and then 3.5mg/kg Azilsartan orally for the following 14 days. Group 6 was given a single injection of 7mg/kg Cisplatin intraperitoneally and then 7mg/kg Azilsartan orally for the following 14 days. Group 7 (standard) was given 25mg/kg/day Resveratrol orally for following 14 days.Azilsartan at low dose (3.5mg/kg) showed a significant reduction in IL-1β pro-inflammatory marker level, whereas there was no significant effect on MDA and SOD levels in cisplatin-induced ocular damage. Histologically, there were significant reduction in inflammatory exudates, edema, and inflammatory cells infiltration with both doses. Additionally, there were no significant difference among Azilsartan only received groups and Resveratrol group. Azilsartan shows a promising anti-inflammatory effect in ocular tissue in Cisplatin experimental rat models by significantly reducing IL-1β overexpression, through its potent AT1receptor blocking effect. However, Azilsartan showed a slight effect on MDA levels and marginal effect on SOD levels in Cisplatin-induced ocular toxicity. Furthermore, Azilsartan at a low dose slightly mimicked the effect of resveratrol on normal ocular tissue, suggesting an advancement in prophylactic application in ocular injury. Keywords: Azilsartan, IL-1β, Cisplatin, Ocular Toxicity

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Section: Discussionsupporting

confidence: 90%

Ameliorating Effect of Azilsartan on Cisplatin -Induced Ocular Toxicity in Male Rats

Mahmood,

Noor Majid Raheem Kareem1

2023

IJPS

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“…BDNF has a critical role on neuronal and glial activity, including cell development, differentiation and plasticity. Saral et al (2021) recently demonstrated that cisplatin administration reduced expression of BDNF/TrkB, restored by the treatment with the anti‐inflammatory compound apelin‐13. It is important to note that the samples in this study were collected 37 days after the first injection of cisplatin, and our samples were obtained on the 14th day, which could account for this discrepancy.…”

Section: Discussionmentioning

confidence: 99%

A partial agonist of PPARγ prevents paclitaxel‐induced peripheral neuropathy in mice, by inhibiting neuroinflammation

Benvenutti,

Wolff,

Corrêa

et al. 2023

British J Pharmacology

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Background and PurposeChemotherapy‐induced peripheral neuropathy (CIPN) is a common side effect of paclitaxel (PTX), affecting 30 to 50% of patients. The increase in survival rate and the concern with patients' quality of life have encouraged the search for new tools to prevent PTX‐induced neuropathy. This study presents the glitazone 4‐[(Z)‐(2,4‐dioxo‐1,3‐thiazolidin‐5‐ylidene)methyl]‐N‐phenylbenzene‐sulfonamide (TZD‐A1) as PPARγ partial‐agonist, its toxicological profile, and effect on PTX‐induced CIPN in mice.Experimental ApproachThe interaction of TZD‐A1 with PPARγ was tested using in silico docking analysis and in vitro reporter gene assay. The pharmacokinetics and toxicity were evaluated using in silico, in vitro and in vivo analysis. The effects of TZD‐A1 on CIPN were investigated in PTX‐injected mice. Axonal and DRG damage, mitochondrial complex activity, and cytokine levels, BDNF, Nrf2 and PPARγ were also evaluated.Key ResultsDocking analysis predicted TZD‐A1 interaction with PPARγ compatible for partial agonists, data corroborated by the in vitro reporter gene assay. TZD‐A1 presented oral bioavailability and safety profile evidenced by in silico, in vitro and in vivo experiments. PTX‐injected mice, concomitantly treated with TZD‐A1 by systemic or oral route, presented reduction of mechanical and thermal hypersensitivity. The mechanisms involved in TZD‐A1 effect seem to be the inhibition of neuroinflammation and mitochondrial damage by increasing Nrf2 and PPARγ levels together with BDNF upregulation.Conclusion and ImplicationsTZD‐A1, partially activating PPARγ, caused neuroprotection and reduced the hypersensitivity induced by PTX. Allied to its safety profile and good bioavailability, TZD‐A1 is a promising drug candidate to prevent and treat CIPN in cancer patients.

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“…Recently, the involvement of neurotrophic factors in the development of depression has also been emphasized. BDNF, as a member of the neurotrophic factor family, is a pivotal indicator of antidepressant treatment in clinical and animal models [ 83 ]. Apelin-13 activates PI3K/Akt signaling pathways related to the activation of BDNF/TrkB [ 84 ].…”

Section: Apelin/apj System Is Involved In Psychosismentioning

confidence: 99%

Apelin/APJ system: an emerging therapeutic target for neurological diseases

Zhao

Chen

et al. 2022

Mol Biol Rep

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Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is extensively expressed in various systems, especially the nervous system. This article reviews the role of apelin/APJ system in neurological diseases. In detail, apelin/APJ system can relieve acute brain injury including subarachnoid hemorrhage, traumatic brain injury, and ischemic stroke. Also, apelin/APJ system has therapeutic effects on chronic neurodegenerative disease models, involving the regulation of neurotrophic factors, neuroendocrine, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy. In addition, through different routes of administration, apelin/APJ system has a biphasic effect on depression, epilepsy, and pain. However, apelin/APJ system exacerbates the proliferation and invasion of glioblastoma. Thus, apelin/APJ system is expected to be a therapeutic target for the treatment of nervous system diseases.

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Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction

Cited by 20 publications

References 39 publications

Ameliorating Effect of Azilsartan on Cisplatin -Induced Ocular Toxicity in Male Rats

Ameliorating Effect of Azilsartan on Cisplatin -Induced Ocular Toxicity in Male Rats

A partial agonist of PPARγ prevents paclitaxel‐induced peripheral neuropathy in mice, by inhibiting neuroinflammation

Apelin/APJ system: an emerging therapeutic target for neurological diseases

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